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.     

Reactive Robust Routing: Anomaly Localization and Routing Reconfiguration for Dynamic Networks

This paper presents a novel approach to deal with dynamic and highly uncertain traffic in dynamic network scenarios. The Reactive Robust Routing (RRR) approach is introduced, a combination of proactive and reactive techniques to improve network efficiency and robustness, simplifying network operation. RRR optimizes routing for normal-operation traffic, using a time-varying extension of the already established Robust Routing technique that outperforms the stable approach. To deal with anomalous and unexpected traffic variations, RRR uses a fast anomaly detection and localization algorithm that rapidly detects and localizes abrupt changes in traffic flows, permitting an accurate routing adaptation. This algorithm presents well-established optimality properties in terms of detection/localization rates and localization delay, which allows for generalization of results, independently of particular evaluations. The algorithm is based on a novel parsimonious model for traffic demands which allows for detection of anomalies using easily available aggregated-traffic measurements, reducing the overheads of data collection.     

The Role of Histone Acetylation-/Methylation-Mediated Apoptotic Gene Regulation in Hepatocellular Carcinoma

Epigenetics, an inheritable phenomenon, which influences the expression of gene without altering the DNA sequence, offers a new perspective on the pathogenesis of hepatocellular carcinoma (HCC). Nonalcoholic steatohepatitis (NASH) is projected to account for a significant share of HCC incidence due to the growing prevalence of various metabolic disorders. One of the major molecular mechanisms involved in epigenetic regulation, post-translational histone modification seems to coordinate various aspects of NASH which will further progress to HCC. Mounting evidence suggests that the orchestrated events of cellular and nuclear changes during apoptosis can be regulated by histone modifications. This review focuses on the current advances in the study of acetylation-/methylation-mediated histone modification in apoptosis and the implication of these epigenetic regulations in HCC. The reversibility of epigenetic alterations and the agents that can target these alterations offers novel therapeutic approaches and strategies for drug development. Further molecular mechanistic studies are required to enhance information governing these epigenetic modulators, which will facilitate the design of more effective diagnosis and treatment options.     

Phototransformation of water-soluble polymers. Part II: photooxidation of poly(ethylene oxide) in aqueous solution

Poly(ethylene oxide) (PEO) was irradiated in aqueous solution under long wavelengths (λ>300 nm, 20 °C) and in presence of oxygen. The photooxidation of PEO was studied by IR spectrophotometry, viscometry and size exclusion chromatography. The formation of the oxidation photoproducts was studied by infrared analysis of films obtained by evaporation of aliquots of irradiated aqueous solutions. The photoproducts were identified by chemical derivatization treatments coupled with infrared measurements. Viscosimetry and SEC analysis showed that photooxidation was leading to a dramatic decrease of the molecular weights. The influence of the pH of the aqueous solutions was also examined. Unexpected results were obtained for the pH 12 solutions, indicating a strong inhibition of the oxidation.

Comparison with the results obtained in the case of PEO irradiated in the solid state showed that no direct transposition of the knowledge concerning the behavior of the solid polymer could be made.     

Electrochemical formation of a copolymer of 3-methoxyethoxythiophene and thiophene

Summary The electrochemical polymerization of 3-methoxyethoxythiophene yields to a polymer which is soluble in organic solvents. However, the solution is not stable in air. The blue solution, characteristic of the polymer in the doped state, turns to red due to the anion undoping process. We have found that this behaviour can be modified when a copolymerization is performed with thiophene; the copolymer is soluble in organic solvents and stable in air.     

A quantitative study on the influence of ASON/GMPLS on OPEX

ASON/GMPLS is promoted as one of the key technologies to reduce operational expenditures (OPEX) of network operators, since it provides the tools for automating the network operations. This paper gives a detailed model and qualitative analysis of the major OPEX-affecting operation processes in the area of core and metropolitan area transport networks. Moreover, a first quantitative evaluation of the changes in the operational efforts induced by ASON/GMPLS is described. The evaluation shows a significant potential to reduce OPEX, which is to some extent independent of the type of operator.     

Aging and implementation of encoding strategies in the generation of rhymes: The role of executive functions.

This experiment examines whether the age-related decrease in the generation effect of rhymes is mediated by executive functioning. Young and elderly adults read and generated pairs of rhyming words for subsequent recall. Participants were also administered neuropsychological tests (executive and mnemonic functions). Results showed that elderly adults performed less well on the neuropsychological tests and benefited less than the younger participants from the generation effect. Hierarchical regression analyses revealed that the executive functions composite score was correlated with the generation effect and that it accounted for a large proportion of the age-related variance of the size of this measure. This finding supports the view that the age-related decrement in strategic encoding implementation is due to a decrease of executive functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of power level and refill liquid composition on the aerosol output and particle size distribution generated by a new-generation e-cigarette device

The new high-power Electronic Nicotine Delivery System (ENDS) can generate aerosols with higher nicotine concentrations than older ENDS. Aerosol particle sizes affect deposition patterns and then plasma nicotine levels in vapers. Consequently, understanding the factors influencing particle size distribution of high-power ENDS is relevant to assess their performance in terms of nicotine delivery. The particle size distribution and the aerosol output (aerosol mass) were measured using cascade impactors. The effects of the refill liquid composition (80% PG/20% VG vs. 80% VG/20% PG; PG refers to propylene glycol and VG to vegetable glycerin) and the power level of the battery (from 7 W to 22 W) were investigated. The aerosol output increases significantly with the power level following a logarithmic law. The PG/VG ratio also has an impact on the aerosol output. The higher the VG content in the refill liquid, the higher is the aerosol output. Besides, particle size distribution is positively related to the power level, following linear correlations between the mass median aerodynamic diameter (MMAD) and the power level in the range of 7–22 W. A moderate impact of the PG/VG ratio on size distribution is equally observed. Changes in the power level allow the transition between a dominant mode with MMAD from 613 nm to 949 nm. We demonstrated that the power level can strongly change the aerodynamic properties of high-power ENDS, especially at high voltage. Associated with the aerosol nicotine level assessment, MMAD could be determined as a means for comparing ENDS devices and nicotine delivery.

Copyright © 2018 American Association for Aerosol Research     

Using Scaffold Supports to Improve Student Practice and Understanding of an Authentic Inquiry Process in Science

This study addressed computer-supported collaborative scientific inquiries in remote networked schools (Quebec, Canada). Three dyads of Grade 5–6 classrooms from remote locations across the province collaborated using the knowledge-building tool Knowledge Forum. Customized scaffold supports embedded in the online tool were used to support student understanding and practice of an authentic inquiry process. The research studied how the use of the scaffolds could help students to understand and put into practice an authentic inquiry process. Students created notes and used the scaffolds to support their inquiry process; however, without sufficient direct teacher modeling, coherent use of the scaffolds stayed low across activities. Pre- and posttest results show that the students gained a better understanding of the inquiry process, but low posttest scores suggest further need for direct teacher modeling of the inquiry process during science instruction.     

Pipe flow of a dense emulsion: Homogeneous shear‐thinning or shear‐induced migration?

The flow field of a 70% concentrated noncolloidal o/w emulsion in a pipe has been investigated by means of Particle Image Velocimetry in a matched refractive index medium. At steady state and in laminar regime, the shape of axial velocity profiles is not parabolic and exhibits a shear‐thinning behavior of the dense emulsion, with a flow index of 0.5 and a negligible yield stress (less than 1 Pa). However, instead of a square root law, the pressure drop increases linearly with U_m. To explain this apparent inconsistency, two mechanisms of different nature are considered. The first originates from a possible relation between the consistency factor and the drop mean diameter. The second mechanism is shear‐induced migration and leads to the development of a concentration gradient in the pipe cross section. Both mechanisms considered reconcile the experimental data, the apparent local shear‐thinning behavior and the linear evolution of the pressure drop with the flow rate. © 2017 American Institute of Chemical Engineers AIChE J, 2017