Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis,Characterization, and Evaluation

There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; M_W 6–9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy.     

Virtual RF system platform dedicated to heterogeneous complex SoC design

In this paper, we propose to develop a hierarchical library associated with various simulators that can be used in a single platform, called TrustMe-ViP, which enables a unique simulation framework and full model interoperability. Such platform is dedicated to complex SoC design, such as trusted personal devices where cost and time-to-market are very important constraints. To validate this methodology, we present the estimation of BER and power consumption for a Bluetooth transceiver.     

Online-Based Kinetic Analysis of Higher Alcohol and Ester Synthesis During Winemaking Fermentations

The production of the major volatile carbon compounds corresponding to the predominant higher alcohols and esters synthesized during wine alcoholic fermentation was monitored using an online GC system. The accuracy and frequency of measurements made it possible to calculate kinetic parameters, in particular rates and specific rates of production. Using this original GC system and a model describing the evolution of the gas–liquid ratio during the fermentation process, kinetic gas–liquid balances of the synthesis of volatile compounds could be followed. This showed that, for esters—substantial proportions of which are lost in the off-gas (up to 40 % of the total production at 20 °C)—measurements of the liquid concentration, rather than of the total production (liquid content?+?losses), can lead to misinterpretations of yeast metabolism. The specific production rate of individual higher alcohols reached their maximum values before the exhaustion of the corresponding precursor amino acids. Isobutanol and isoamyl alcohol were formed from carbon metabolites and nitrogen metabolites and consequently were produced continuously throughout the fermentation process. In contrast, propanol synthesis was strongly correlated with the presence of assimilable nitrogen, during both the growth and stationary phases. Therefore, propanol appears to be a highly pertinent marker of nitrogen metabolism. Acetate ester concentrations correlated linearly with the concentrations of the corresponding higher alcohols, indicating that the availability of the precursors is the main limiting factor for the production of these esters. These results open possibilities for innovative approaches based on metabolic flux analysis and taking their dynamics into account.     

Quality Map Thresholding for De-noising of Complex-Valued fMRI Data and Its Application to ICA of fMRI

Although functional magnetic resonance imaging (fMRI) data are acquired as complex-valued images, traditionally most fMRI studies only use the magnitude of the data. FMRI analysis in the complex domain promises to provide more statistically significant information; however, the noisy nature of the phase poses a challenge for successful study of fMRI by complex-valued signal processing algorithms. In this paper, we introduce a physiologically motivated de-noising method that uses phase quality maps to successfully identify and eliminate noisy areas in the fMRI data so they can be used in individual and group studies. Additionally, we show how the developed de-noising method improves the results of complex-valued independent component analysis of fMRI data, a very successful tool for blind source separation of biomedical data.     

Hospitalization for acute pyelonephritis in Manitoba, Canada, during the period from 1989 to 1992; impact of diabetes, pregnancy, and aboriginal origin

Population-based rates of hospitalization for acute pyelonephritis were estimated over 3 years with use of provincial administrative data on health care. Retrospective review of records of ICD9-CM discharge codes of pyelonephritis and urinary infection was performed in two acute care institutions to validate the discharge diagnosis; 80% of patients with a discharge diagnosis of pyelonephritis and 7% to 20% of patients with a discharge diagnosis of urinary infection met clinical criteria for admission for acute pyelonephritis. Mean rates of hospitalization +/- SD for acute pyelonephritis were 10.86 +/- 0.51 per 10,000 population among women and 3.32 +/- 0.27 per 10,000 population among men. From 18% to 31% of hospitalized women aged 20-39 years pregnant; 36% of 797 hospitalized women and 21% of 402 hospitalized men 40 years of age or older were diabetic. The hospitalization rates among Native American women with treaty status were five to 20 times greater than those among other women, which was partially attributable to a significantly greater frequency of pregnancy and diabetes in the former women. Hospitalization for acute pyelonephritis is common, and pregnancy and diabetes contribute substantially to hospitalization rates. The increased hospitalization rate among Native American women with treaty status is not fully explained by pregnancy or diabetes.     

The mechanism of whisker growth in the reduction of wüstite

The growth of iron whiskers on wüstite is explained on the basis of C. Wagner’s mechanism for the reduction of nonstoichiometric oxides. The first metal nucleus develops into a whisker if the iron accumulation in the supersaturated wustite particle is nearly uniform, a condition which is favored by chemical control. A mathematical model is proposed in which the “filling ratio” of wüstite by iron prior to nucleation is expressed in terms of the reaction constant, the chemical diffusion coefficient of iron, the particle radius, the Fe/o ratio at equilibrium with the gas, and the critical Fe/o ratio for nucleation at the most favorable site. The morphology of iron in the early stages of reduction, which goes from a single cylindrical whisker, through sponge iron to a smooth layer, can be predicted by comparing at all times the map of the actual Fe/o ratio at the surface with the map of the local Fe/O ratio for nucleation. A satisfactory test of the theory is obtained through a survey of the experimental evidence available about the effect of several physico-chemical factors of reduction on the iron morphology,e.g. surface characteristics, particle size, composition of the reducing gas, solute cations in wüstite, temperature, and gas transport. Formerly with the Ecole Centrale des Arts et Manufactures, Chătenay-Malabry