Amiens – Rue Isidore-François, rue du Pont-de-Metz

Le diagnostic de la rue Isidore-François fait suite au dépôt d’un projet de lotissement. Il se trouve dans un contexte d’anciennes briqueteries où seules les occupations préhistoriques ont pu être potentiellement conservées. Toutefois, malgré la découverte de niveaux favorables à la conservation (limons fluviatiles fins, limons lités), aucun artefact paléolithique n’a été mis au jour. Néanmoins, les différents faciès observés de la séquence lœssique peuvent être interprétés grâce aux travaux ..

Saint-Sauveur – Zac Les Prés Moireaux

Le projet de création d’une Zac au lieu-dit « Les Prés Moireaux » sur la commune de Saint-Sauveur a été précédé par la réalisation d’un diagnostic archéologique. L’emprise de 55 539 m2, est située dans la plaine alluviale de l’automne, affluent de l’Oise. Historiquement, seule une intervention à quelques centaines de mètres à l’ouest a été réalisée (Verberie, « La Main levée » ; Malrain 2009). Au niveau géomorphologique, deux contextes différents ont été observés : d’une part une butte tertia..

Guiscard – Rue de la Tombelle

Le projet de création d’un lotissement sur la commune de Guiscard sur une surface de 51 337 m2 a été précédé par la réalisation d’un diagnostic archéologique. Le contexte archéologique est relativement pauvre : seuls quelques indices gallo-romains et l’origine médiévale (xe s.) de Guiscard sont attestés. Une occupation datée de La Tène finale au Haut-Empire a été mise au jour. La plus forte densité de vestiges est située dans le quart sud-est de l’emprise (environ 12 000 m2). La période de La..

Amiens – Zac de Renancourt (tranche 2)

À Amiens, la future Zac de Renancourt occupera 53 ha et doit faire l’objet d’un diagnostic archéologique complet. Après une première tranche de 44 ha réalisée en 2007 par L. Duvette, cette seconde tranche concerne 9 371 m2. Elle est située dans un secteur au contexte archéologique riche, avec notamment la proximité immédiate à l’ouest d’un locus gravettien fouillé par V. Commont en 1910, et redécouvert en 1996 par J.-P. Fagnart qui précisa l’extension du gisement et sa chronostratigraphie. Ce..

Chézy-sur-Marne – Le Colombier

Le diagnostic archéologique réalisé à Chézy-sur-Marne au lieu-dit « Le Colombier » a révélé trois occupations différentes. D’une surface de 54 915 m2, l’emprise est située sur un versant abrupt orienté vers l’est. Les vestiges sont tous situés sur la partie haute du versant, là où la pente est plus faible et favorable à l’implantation humaine. D’un point de vue géomorphologique, les sondages profonds ont permis de repérer les grandes lignes de la sédimentation limoneuse sur ce versant : à par..

Antisense Oligonucleotides, A Novel Developing Targeting Therapy

Antisense oligonucleotides (ASOs) have been validated as therapeutic agents and an important tool in molecular biology. Indeed, ASOs are used either in vitro or in vivo to generate mRNA selective knockouts. They can be used for human therapy since ASOs can inhibit specifically target genes especially whose are difficult to target with small molecules inhibitors or neutralizing antibodies. However, despite their specificity and broadness of use, some practical obstacles remain unsolved in antisense pharmacology, such as insufficient stability due to nucleases degradation activity, and poor cellular delivery as a result of low cellular uptake difficult biological membrane crossing. Moreover, in many cases, potential off-target effects and immunostimulation are also part of the problems derived from their use. In this review, we will discuss ASOs, their chemistry, limitation of use, some solutions to increase stability, and finally some of their therapeutical application

Exploiting protected maleimides to modify oligonucleotides, peptides and peptide nucleic acids

This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon heating, which can be followed by either Michael-type or Diels-Alder click conjugation reactions. However, the one-pot procedure in which maleimide deprotection and conjugation are simultaneously carried out provides the target conjugate more quickly and, more importantly, in better yield. This procedure is compatible with conjugates involving oligonucleotides, peptides and peptide nucleic acids. A variety of cyclic peptides and oligonucleotides can be obtained from peptide and oligonucleotide precursors incorporating protected maleimides and thiols

Rational design of novel N-alkyl-N capped biostable RNA nanostructures for efficient long-term inhibition of gene expression

Computational techniques have been used to design a novel class of RNA architecture with expected improved resistance to nuclease degradation, while showing interference RNA activity. The in silico designed structure consists of a 24–29 bp duplex RNA region linked on both ends by N-alkyl-N dimeric nucleotides (BCn dimers; n = number of carbon atoms of the alkyl chain). A series of N-alkyl-N capped dumbbell-shaped structures were efficiently synthesized by double ligation of BCn-loop hairpins. The resulting BCn-loop dumbbells displayed experimentally higher biostability than their 3′-N-alkyl-N linear version, and were active against a range of mRNA targets. We studied first the effect of the alkyl chain and stem lengths on RNAi activity in a screen involving two series of dumbbell analogues targeting Renilla and Firefly luciferase genes. The best dumbbell design (containing BC6 loops and 29 bp) was successfully used to silence GRB7 expression in HER2+ breast cancer cells for longer periods of time than natural siRNAs and known biostable dumbbells. This BC6-loop dumbbell-shaped structure displayed greater anti-proliferative activity than natural siRNAs.Instituto de Salud Carlos III [Miguel Servet Program, CP13/00211, 205024141 to M.T.]; Spanish MINECO [BIO2012–32869 and BIO2015-64802-R toM.O.]; AGAUR (toM.O.); ERCCouncil (SimDNA, grant 291433, to M.O.). M.O. is an ICREA Academia fellow. Funding for open access charge: ERC Council [grant 291433 (simDNA)].Peer ReviewedPostprint (published version

The Application of X-Band Radar for Characterisation of Nearshore Dynamics on a Mixed Sand and Gravel Beach

Remote sensing using X-band radar allows the estimation of wave parameters, near surface currents and the underlying bathymetry. This paper explores the use of radar to derive nearshore bathymetry at a complex site, at Thorpeness in Suffolk, UK. The site has a history of sporadic and focused erosion events along the beach frontage and as part of the X-Com project (X-band Radar and Evidence-Based Coastal Management Decisions) a radar system was deployed with the aim of further understanding the complex nearshore sediment processes influencing erosion. Initially, the bathymetric variation at the site is quantified through analysis of current and historic multibeam surveys. These indicate depth changes approaching 3 m. Subsequently, validation of the radar data against concurrent multibeam survey data has been undertaken. Results show that the radar derived bathymetry has a precision of ±1m at the site, with the largest errors being associated with areas of more complex bathymetry and where wave data quality was less suitable for analysis by the X-band radar bathymetry algorithms. It is concluded that although the accuracy of radar-derived bathymetry is lower than traditional multibeam survey, the low cost for high temporal coverage can be utilised for long-term monitoring of coastal sites where a cost-effective means of quantifying large-scale bathymetric changes is required

Zip Nucleic Acids: new high affinity oligonucleotides as potent primers for PCR and reverse transcription

Most nucleic acid-based technologies rely upon sequence recognition between an oligonucleotide and its nucleic acid target. With the aim of improving hybridization by decreasing electrostatic repulsions between the negatively charged strands, novel modified oligonucleotides named Zip nucleic acids (ZNAs) were recently developed. ZNAs are oligonucleotide–oligocation conjugates whose global charge is modulated by the number of cationic spermine moieties grafted on the oligonucleotide. It was demonstrated that the melting temperature of a hybridized ZNA is easily predictable and increases linearly with the length of the oligocation. Furthermore, ZNAs retain the ability to discriminate between a perfect match and a single base-pair-mismatched complementary sequence. Using quantitative PCR, we show here that ZNAs are specific and efficient primers displaying an outstanding affinity toward their genomic target. ZNAs are particularly efficient at low magnesium concentration, low primer concentrations and high annealing temperatures, allowing to improve the amplification in AT-rich sequences and potentially multiplex PCR applications. In reverse transcription experiments, ZNA gene-specific primers improve the yield of cDNA synthesis, thus increasing the accuracy of detection, especially for genes expressed at low levels. Our data suggest that ZNAs exhibit faster binding kinetics than standard and locked nucleic acid-containing primers, which could explain why their target recognition is better for rare targets