Dynamic characterisation of interlaminar fracture toughness in carbon fibre epoxy composite laminates

In this work, the rate dependence of mode I interlaminar fracture toughness for two different materials systems, IM7/8552 and IM7/M91, both unidirectional UD carbon-fibre epoxy composite laminates have been examined over a wide range of loading rates from 0.5 mm/min up to 2000 mm/s at room temperature. Quasi-static fracture tests were performed using a DCB (double-cantilever beam) method with a screw-driven testing machine, while the dynamic tests were carried out using a WIF (wedge-insert fracture) specimen loaded dynamically in a hydraulic system. For performing the tests at high displacement rates, a special setup was designed and manufactured which allowed the insertion of the wedge within the DCB specimens at different cross-head displacement rates. The experimental technique used a pair of strain gauges attached to the bending surface of one of the arms of the cantilever beams and far from the initial crack tip. The peak values of the recorded strain were used to determine the fracture toughness under dynamic conditions through use of the compliance calibration method. A finite element model was developed to check the consistency of the measurements and validate the data reduction method used. The results exhibited rate insensitive behaviour in the case of the IM7/8552 laminates while IM7/M91 showed the contrary behaviour with maximum peak at 500 mm/s of displacement rate, with a toughness increase of 95% with respect to the quasi-static conditions.The research leading to these results has received funding from the European Union as Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 722096, DYNACOMP project

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Enhanced anti-HIV-1 activity of G-quadruplexes comprising locked nucleic acids and intercalating nucleic acids

Two G-quadruplex forming sequences, 5′-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating nucleic acid, TINA). Incorporation of LNA or INA/TINA monomers provide as much as 8-fold improvement of anti-HIV-1 activity. We demonstrate for the first time a detailed analysis of the effect the incorporation of INA/TINA monomers in quadruplex forming oligonucleotides (QFOs) and the effect of LNA monomers in the context of biologically active QFOs. In addition, recent literature reports and our own studies on the gel retardation of the phosphodiester analogue of T30177 led to the conclusion that this sequence forms a parallel, dimeric G-quadruplex. Introduction of the 5′-phosphate inhibits dimerisation of this G-quadruplex as a result of negative charge–charge repulsion. Contrary to that, we found that attachment of the 5′-O-DMT-group produced a more active 17-mer sequence that showed signs of aggregation—forming multimeric G-quadruplex species in solution. Many of the antiviral QFOs in the present study formed more thermally stable G-quadruplexes and also high-order G-quadruplex structures which might be responsible for the increased antiviral activity observed

Stability and kinetics of G-quadruplex structures

In this review, we give an overview of recent literature on the structure and stability of unimolecular G-rich quadruplex structures that are relevant to drug design and for in vivo function. The unifying theme in this review is energetics. The thermodynamic stability of quadruplexes has not been studied in the same detail as DNA and RNA duplexes, and there are important differences in the balance of forces between these classes of folded oligonucleotides. We provide an overview of the principles of stability and where available the experimental data that report on these principles. Significant gaps in the literature have been identified, that should be filled by a systematic study of well-defined quadruplexes not only to provide the basic understanding of stability both for design purposes, but also as it relates to in vivo occurrence of quadruplexes. Techniques that are commonly applied to the determination of the structure, stability and folding are discussed in terms of information content and limitations. Quadruplex structures fold and unfold comparatively slowly, and DNA unwinding events associated with transcription and replication may be operating far from equilibrium. The kinetics of formation and resolution of quadruplexes, and methodologies are discussed in the context of stability and their possible biological occurrence

Detecting impacts of invasive non-native sharptooth catfish, Clarias gariepinus, within invaded and non-invaded rivers.

In aquatic ecosystems, impacts by invasive introduced fish can be likened to press disturbances that persistently influence communities. This study examined invasion disturbances by determining the relationship between non-native sharptooth catfish Clarias gariepinus and aquatic macroinvertebrates in the Eastern Cape, South Africa. A Multiple Before–After Control–Impact (MBACI) experimental design was used to examine macroinvertebrate communities within two rivers: one with catfish and another one without catfish. Within the invaded river, macroinvertebrates showed little response to catfish presence, whereas predator exclusion appeared to benefit community structure. This suggests that the macroinvertebrate community within the invaded river was adapted to predation impact because of the dominance of resilient taxa, such as Hirudinea, Oligochaeta and Chironomidae that were abundant in the Impact treatment relative to the Control treatment. High macroinvertebrate diversity and richness that was observed in the Control treatment, which excluded the predator, relative to the Impact treatment suggests predator avoidance behaviour within the invaded river. By comparison, within the uninvaded river, catfish introduction into the Impact treatment plots indicated negative effects on macroinvertebrate community that was reflected by decrease in diversity, richness and biomass. A community level impact was also reflected in the multivariate analysis that indicated more variation in macroinvertebrate composition within the Impact treatment relative to the Control in the uninvaded river. Catfish impact within the uninvaded river suggests the dominance of vulnerable taxa, such as odonates that were less abundant in the Impact treatment plots after catfish introduction. From a disturbance perspective, this study revealed different macroinvertebrate responses to catfish impact, and suggests that within invaded habitats, macroinvertebrates were less responsive to catfish presence, whereas catfish introduction within uninvaded habitats demonstrated invasion impact that was shown by a decrease in the abundance of vulnerable taxa. The occurrence of non-native sharptooth catfish within many Eastern Cape rivers is a concern because of its predation impact and potential to influence trophic interrelationships, and efforts should be taken to protect uninvaded rivers, and, where possible, eradicate the invader