Incorporation of aptamers in the terminal loop of shRNAs yields an effective and novel combinatorial targeting strategy.

Gene therapy by engineering patient's own blood cells to confer HIV resistance can potentially lead to a functional cure for AIDS. Toward this goal, we have previously developed an anti-HIV lentivirus vector that deploys a combination of shRNA, ribozyme and RNA decoy. To further improve this therapeutic vector against viral escape, we sought an additional reagent to target HIV integrase. Here, we report the development of a new strategy for selection and expression of aptamer for gene therapy. We developed a SELEX protocol (multi-tag SELEX) for selecting RNA aptamers against proteins with low solubility or stability, such as integrase. More importantly, we expressed these aptamers in vivo by incorporating them in the terminal loop of shRNAs. This novel strategy allowed efficient expression of the shRNA-aptamer fusions that targeted RNAs and proteins simultaneously. Expressed shRNA-aptamer fusions targeting HIV integrase or reverse transcriptase inhibited HIV replication in cell cultures. Viral inhibition was further enhanced by combining an anti-integrase aptamer with an anti-HIV Tat-Rev shRNA. This construct exhibited efficacy comparable to that of integrase inhibitor Raltegravir. Our strategy for the selection and expression of RNA aptamers can potentially extend to other gene therapy applications

Tug-of-War games and the infinity Laplacian with spatial dependence

In this paper we look for PDEs that arise as limits of values of Tug-of-War games when the possible movements of the game are taken in a family of sets that are not necessarily euclidean balls. In this way we ¯nd existence of viscosity solutions to the Dirichlet problem for an equation of the form ¡hD 2 v ¢ Jx(Dv); Jx(Dv)i(x) = 0, that is, an in¯nity Laplacian with spatial dependence. Here Jx(Dv(x)) is a vector that depends on the the spatial location and the gradient of the solution.Fil: Gomez, Ivana Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Santa Fe. Instituto de Matemática Aplicada; Argentina;Fil: Rossi, Julio Daniel. Universidad de Buenos Aires; Argentina

MASSIVE CODESIGN

This book focuses on “massive codesign”: the idea that multiple and/or numerous participants having different voices collaborate in a design pro- cess broken down into different steps and formats and resulting in a relevant and diversified amount of data. Services, strategies and scenarios are presented as the main field of ap- plication: these are complex items that demand complex processes be tac- kled, processes in which it is necessary to involve a variety of players who are largely interdependent and therefore who must collaborate in order to achieve any goal. The book essentially makes two main contributions: a “Collaborative De- sign Framework” to identify and structure codesign activities, methods and tools within massive creative processes; a “set of quick lessons learnt” to provide guidance to the conception and organisation of other massive crea- tive processes. The whole book is oriented at practice: it discusses codesign activities from the designer’s point of view, detailing issues such as process from beginning to end, activity flow, manipulability of tools, roles and rules for participants and many others. It is intended as a support for designers dealing in massive codesign processes and aims towards improved results

Inhibition of inducible Nitric Oxide Synthase expression by an acetonic extract from Feijoa sellowiana Berg. fruits.

Feijoa sellowiana Berg. fruits and especially the acetonic extract have been shown to possess biological activities, although the responsible compounds have never been identified. The present study was designed to evaluate the anti-inflammatory activity of an acetonic extract from F. sellowiana Berg. fruits on the nitric oxide (NO) pathway, which plays an important role in inflammation. To this aim the J774 cell line, which expresses inducible nitric oxide synthase (iNOS) following stimulation with lipopolysaccharide (LPS), has been utilized, and the effects of this extract and its fractions on NO production, iNOS protein expression, and signal pathways involved in its regulation have been evaluated. This study demonstrates that at least some part of the anti-inflammatory activity of the acetonic extract is due to the suppression of NO production by flavone and stearic acid. The mechanism of this inhibition seems to be related to an action on the expression of the enzyme iNOS through the attenuation of nuclear factor κB (NF-κB) and/or mitogen-activated protein kinase (MAPK) activation

How Pro-social Framing Affects the Success of Crowdfunding Projects: The Role of Emphasis and Information Crowdedness

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Biohydrogen production from food waste: Influence of the inoculum-to-substrate ratio

In this study, the influence of the inoculum-to-substrate ratio (ISR) on dark fermentative hydrogen production from food waste (FW) was evaluated. ISR values ranging from 0.05 to 0.25 g VSinoculum/g VSsubstrate were investigated by performing batch tests at T = 39 °C and pH = 6.5, the latter being the optimal value identified based on a previous study. The ISR was found to affect the fermentation process, clearly showing that an adequate ISR is essential in order to optimise the process kinetics and the H2 yield. An ISR of 0.14 proved to optimum, leading to a maximum H2 yield of 88.8 L H2/kg VSFW and a maximum production rate of 10.8 L H2/kg VSFW∙h. The analysis of the fermentation products indicated that the observed highest H2 production mostly derived from the typical acetate/butyrate-type fermentation

Massive Codesign

"This book focuses on ""massive codesign"": the idea that multiple and/or numerous participants having different voices collaborate in a design process broken down into different steps and formats and resulting in a relevant and diversified amount of data. Services, strategies and scenarios are presented as the main field of application: these are complex items that demand complex processes be tackled, processes in which it is necessary to involve a variety of players who are largely interdependent and therefore who must collaborate in order to achieve any goal. The book essentially makes two main contributions: a ""Collaborative Design Framework"" to identify and structure codesign activities, methods and tools within massive creative processes; a ""set of quick lessons learnt"" to provide guidance to the conception and organisation of other massive creative processes. The whole book is oriented at practice: it discusses codesign activities from the designer's point of view, detailing issues such as process from beginning to end, activity flow, manipulability of tools, roles and rules for participants and many others. It is intended as a support for designers dealing in massive codesign processes and aims towards improved results.