Dioctadecyldimethylammonium:monoolein nanocarriers for efficient in vitro gene silencing

This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid monoolein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery.This work was supported by FEDER through POFC - COMPETE and by national funds from FCT through the projects PEst-C/BIA/UI4050/2011 (CBM.A), PEst-C/FIS/UI0607/2011 (CFUM), and PTDC/QUI/69795/2006, while Ana Oliveira holds scholarship SFRH/BD/68588/2010. Eloi Feitosa thanks FAPESP (2011/03566-0) and CNPq (303030/2012-7), and Renata D. Adati thanks FAPESP for scholarship (2011/07414-0). K. Raemdonck is a postdoctoral fellow of the Research Foundation - Flanders (FWO-Vlaanderen). We acknowledge NanoDelivery-I&D em Bionanotecnologia, Lda. for access to their equipment

Continuum tensor network field states, path integral representations and spatial symmetries

A natural way to generalize tensor network variational classes to quantum field systems is via a continuous tensor contraction. This approach is first illustrated for the class of quantum field states known as continuous matrix-product states (cMPS). As a simple example of the path-integral representation we show that the state of a dynamically evolving quantum field admits a natural representation as a cMPS. A completeness argument is also provided that shows that all states in Fock space admit a cMPS representation when the number of variational parameters tends to infinity. Beyond this, we obtain a well-behaved field limit of projected entangled-pair states (PEPS) in two dimensions that provide an abstract class of quantum field states with natural symmetries. We demonstrate how symmetries of the physical field state are encoded within the dynamics of an auxiliary field system of one dimension less. In particular, the imposition of Euclidean symmetries on the physical system requires that the auxiliary system involved in the class' definition must be Lorentz-invariant. The physical field states automatically inherit entropy area laws from the PEPS class, and are fully described by the dissipative dynamics of a lower dimensional virtual field system. Our results lie at the intersection many-body physics, quantum field theory and quantum information theory, and facilitate future exchanges of ideas and insights between these disciplines

Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s

PURPOSE: Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity. METHODS: We report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex. RESULTS: PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity. CONCLUSIONS: PEGylated poly(amido amine)s are promising carriers for systemic siRNA delivery in vivo

A stereo music pre-processing scheme for cochlear implant users

OBJECTIVE: Listening to music is still one of the more challenging aspects of using a cochlear implant (CI) for most users. Simple musical structures, a clear rhythm/beat, and lyrics that are easy to follow are among the top factors contributing to music appreciation for CI users. Modifying the audio mix of complex music potentially improves music enjoyment in CI users. METHODS: A stereo music preprocessing scheme is described in which vocals, drums, and bass are emphasized based on the representation of the harmonic and the percussive components in the input spectrogram, combined with the spatial allocation of instruments in typical stereo recordings. The scheme is assessed with postlingually deafened CI subjects (N = 7) using pop/rock music excerpts with different complexity levels. RESULTS: The scheme is capable of modifying relative instrument level settings, with the aim of improving music appreciation in CI users, and allows individual preference adjustments. The assessment with CI subjects confirms the preference for more emphasis on vocals, drums, and bass as offered by the preprocessing scheme, especially for songs with higher complexity. CONCLUSION: The stereo music preprocessing scheme has the potential to improve music enjoyment in CI users by modifying the audio mix in widespread (stereo) music recordings. SIGNIFICANCE: Since music enjoyment in CI users is generally poor, this scheme can assist the music listening experience of CI users as a training or rehabilitation tool.status: publishe

Take-home evaluation of music pre-processing scheme with cochlear implant users

status: publishe