Post-cracking tensile behaviour of steel-fibre-reinforced roller-compacted-concrete for FE modelling and design purposes

Fracture of steel-fibre-reinforced-concrete occurs mostly in the form of a smeared crack band undergoing progressive microcracking. For FE modelling and design purposes, this crack band could be characterised by a stress-strain (σ-ε) relationship. For industrially-produced steel fibres, existing methodologies such as RILEM TC 162-TDF (2003) propose empirical equations to predict a trilinear σ-ε relationship directly from bending test results. This paper evaluates the accuracy of these methodologies and their applicability for rollercompacted-concrete and concrete incorporating steel fibres recycled from post-consumer tyres. It is shown that the energy absorption capacity is generally overestimated by these methodologies, sometimes up to 60%, for both conventional and roller-compacted concrete. Tensile behaviour of fibre-reinforced-concrete is estimated in this paper by inverse analysis of bending test results, examining a variety of concrete mixes and steel fibres. A multilinear relationship is proposed which largely eliminates the overestimation problem and can lead to safer designs

4D BIM integrated construction supply chain logistics to optimise on-site production

Loss of productivity through on-site delays and disruptions is a significant problem in the construction industry. This can be caused by workforce, materials, and equipment clashes. A major need for the industry is to improve construction logistic efficiencies for materials and equipment from manufacture to the point of use by the workforce. The authors investigate the effectiveness and efficiency of integrated construction supply chain logistics (ICSCL) using 4D Building Information Models (BIM), via three information streams: literature, a case study of the Elephant and Castle project (E&C), and a survey from UK construction professionals. The results illustrate, although BIM of various levels is currently in use throughout the UK, 4D BIM for ICSCL is not extensively utilised due to an absence of strategy, perceived costs of IT, and training requirements. That use could potentially add value with a trusted supply chain and disciplined planning using a multiple stream logistic model

HuR protein attenuates miRNA-mediated repression by promoting miRISC dissociation from the target RNA

The microRNA (miRNA)-mediated repression of protein synthesis in mammalian cells is a reversible process. Target mRNAs with regulatory AU-rich elements (AREs) in their 3′-untranslated regions (3′-UTR) can be relieved of miRNA repression under cellular stress in a process involving the embryonic lethal and altered vision family ARE-binding protein HuR. The HuR-mediated derepression occurred even when AREs were positioned at a considerable distance from the miRNA sites raising questions about the mechanism of HuR action. Here, we show that the relief of miRNA-mediated repression involving HuR can be recapitulated in different in vitro systems in the absence of stress, indicating that HuR alone is sufficient to relieve the miRNA repression upon binding to RNA ARE. Using in vitro assays with purified miRISC and recombinant HuR and its mutants, we show that HuR, likely by its property to oligomerize along RNA, leads to the dissociation of miRISC from target RNA even when miRISC and HuR binding sites are positioned at a distance. Further, we demonstrate that HuR association with AREs can also inhibit miRNA-mediated deadenylation of mRNA in the Krebs-2 ascites extract, in a manner likewise depending on the potential of HuR to oligomerize

MicroRNAs as new maestro conducting the expanding symphony orchestra of regenerative and reparative medicine

The human genome encodes 1,048 microRNAs (miRNAs). These miRNAs regulate virtually all biological processes. Leaving ignominy on the significance miRNAs behind we are approaching a new era in tissue repair where an ever expanding orchestra of events that enable tissue repair and regeneration seems to be conducted by miRNAs as the maestro. microRNAs are emerging as molecular rheostats that fine-tune and switch regulatory circuits governing tissue repair. Key elements of tissue repair such as stem cell biology, inflammation, hypoxia-response, and angiogenesis are all under the sophisticated control of a network of specific mRNAs. Embryonic stem cells lacking miRNAs lose their “stemness.” Manipulation of specific cellular miRNAs helps enhance reprogramming of somatic cells to an embryonic stem cell-like phenotype helping generate inducible pluripotent stem cells. Expression of miRNAs is subject to control by epigenetic factors. Such control influences the balance between proliferation and differentiation of stem cells. Angiomirs regulate various aspects of angiogenesis, such as proliferation, migration, and morphogenesis of endothelial cells. MiRNAs play a key role in resolution of inflammation. Hypoxia-inducible mRNAs or hypoxamirs suppress mitochondrial respiration, cause cell cycle arrest, and interfere with growth factor signaling. miRNA-210 is a good example in this category that impairs wound closure. As fine tools enabling specific and temporally controlled manipulation of cell-specific miRNAs emerge, miRNA-based therapies hold promise in facilitating tissue repair. Treatment of skin wounds has lower barriers because it lends itself to local delivery of miRNA mimics and antagonizing agents minimizing risks associated with systemic off-target toxicity

The expression levels of microRNA-361-5p and its target VEGFA are inversely correlated in human cutaneous squamous cell carcinoma

Vascular endothelial growth factor A (VEGFA) plays a key role in the angiogenesis of human skin. Elevated levels of VEGFA are associated with several pathological conditions, including chronic inflammatory skin diseases and several types of skin cancer. In particular, squamous cell carcinoma (SCC) of the skin, the second most common skin cancer in the general population, is characterized by invasive growth, pronounced angiogenesis and elevated levels of VEGFA. The processing, turnover and production of VEGFA are extensively regulated at the post-transcriptional level, both by RNA-binding proteins and microRNAs (miRNAs). In the present study, we identified a new miRNA recognition element in a downstream conserved region of the VEGFA 3'-UTR. We confirmed the repressive effect of miR-361-5p on this element in vitro, identifying the first target for this miRNA. Importantly, we found that miR-361-5p levels are inversely correlated with VEGFA expression in SCC and in healthy skin, indicating that miR-361-5p could play a role in cancers