Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes.

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Aortic arch and proximal descending aorta replacement with the Thoraflex* prosthesisAtherosclerotic aneurysm or dissection of the aortic arch and proximal descending thoracic aorta is one of the major challenges for a cardiovascular surgeon. The new hybrid prosthesis Thoraflex has become an important devise to simplify the surgical treatment of this very complex and technically demanding aortic pathology. This hybrid prosthesis consists of a 4-branched arch graft with a stent-graft at the distal end. The proximal part is a gelatin-coated woven polyester prosthesis. The stented section is a self-expanding endoprosthesis constructed of thin-walled polyester and nitinol ring stents that is left in the proximal descending aorta as a "frozen elephant trunk". We present our initial experience with the Thoraflex prosthesis in four patients, three of them with chronic aortic dissection and one with an atherosclerotic aneurysm.

+-+,~he~GTAG.£ovmalismdescrihes.th~domain_ text generation, as defined for the GTAG model used to specify the input of the generator, formalism, and its implementation in the CLEF project. We will show how to use iexical choice constraints and properties of the LTAG grammar to minimize the backtracking of the semirecursive algorithm.