A microscale-based model for small-strain stiffness in unsaturated granular geomaterials

Stiffness at very small strains G 0 is commonly assessed by way of laboratory and field methods, and used to design a wide range of infrastructure. When stiffness is inferred from field measurements, its value depends on the soil suction and state of saturation at the time of the measurement, and models are needed to infer G 0 at varying suction and degree of saturation. When stiffness is measured on saturated specimens in the laboratory, models are needed to extrapolate the laboratory saturated' stiffness to the field unsaturated' stiffness. This paper presents an experimental investigation of G 0 of unsaturated sand using the hanging water column method and the bender element technique. Experimental results revealed that wave propagation velocity and, hence, stiffness is not controlled by the product suction times the degree of saturation'. A microscale-based model was formulated to interpret the experimental results, and to elucidate the mechanisms underlying different patterns of G 0 in unsaturated materials observed in the literature. According to the proposed model, the evolution of G 0 is controlled by the evolution of the suction/degree of saturation-induced intergranular stress during drying-wetting cycles. The breadth of the water retention curve and the magnitude of the intergranular stress due to the presence of the menisci were found to be responsible for the different patterns of G 0

Grouting of well leakage and migration pathways using colloidal silica : a preliminary experimental investigation

Hydrocarbon well decommissioning and abandonment require the long-term sealing of potential fluid migration pathways. Current grouting technologies based on the use of cementitious grouts may not be able to achieve proper penetration and sealing of migration pathways, this resulting in an environmental risk due to the migration of hydrocarbons or other well fluids out of the well and into the environment. Colloidal silica (CS) based grouts differ from traditional cement grouts due to their low viscosity (similar to water), and their excellent penetrability governed by the size of the silica nanoparticles (~15nm). As a result, CS grouts have the potential to seal migration pathways (i) at cement/casing or casing/cement interfaces where the cement bond is compromised, and (ii) due to micro-channels and micro-annuli within the cement annulus. This study presents a preliminary laboratory investigation to demonstrate the suitability of CS grout for the purpose of creating multiple barriers within hydrocarbon wells. To this end, CS grout was injected into fractured cement cores using a high pressure/high temperature core-holder apparatus to simulate target downhole scenarios. Microstructural analysis (micro-CT scanning) prior and post treatment were conducted to image the spatial distribution of the grout within the fracture network. The effectiveness of the treatment was measured by evaluating i) the core permeability before and after treatment with CS, and ii) the unconfined compressive strength of treated cement cores

Exploring the micromechanics of non-active clays by way of virtual DEM experiments

The micromechanical behaviour of clays cannot be investigated experimentally in a direct fashion due to the small size of clay particles. An insight into clay mechanical behaviour at the particle scale can be gained by way of virtual experiments based on the discrete-element method (DEM). So far, most DEM models for clays have been designed on the basis of theoretical formulations of inter-particle interactions, with limited experimental evidence of their actual control over the clay's macroscopic response. This paper presents a simplified two-dimensional DEM framework where contact laws were inferred from indirect experimental evidence at the microscale provided by Pedrotti and Tarantino in 2017 (particle-to-particle interactions were probed experimentally by varying the pore-fluid chemistry, and the resulting effect was explored by way of scanning electron microscopy and mercury intrusion porosimetry). The proposed contact laws were successfully tested against their ability to reproduce qualitatively the compression behaviour of clay with pore fluids of varying pH and dielectric permittivity. The DEM framework presented in this work was intentionally kept simple in order to demonstrate the robustness of the micromechanical concept underlying the proposed contact laws. It is anticipated that a satisfactory quantitative prediction would be achieved by moving to a three-dimensional formulation, by considering polydisperse specimens and by refining the contact laws

Reducing hazard in spent fuel removal using colloidal silica gel

Nuclear site decommissioning involves the retrieval and handling of radioactive waste. Waste removal from nuclear reactors and/or storage facilities, such as spent fuel pools and storage silos, represents a potential hazard in terms of radiation exposure for the workforce and the surrounding environment. This study explores the suitability of colloidal silica grouting around radioactive waste to reduce radiation exposure during retrieval operations. Previous work on colloidal silica gel has proved its potential to form low-permeability hydraulic barriers, and to inhibit the diffusion of radionuclides through the gel, making it a promising material for spent fuel recovery applications. This work provides experimental evidence that colloidal silica hydrogel can maintain its integrity upon exposure to temperatures typical of the nuclear waste stored within pools and silos, both in standard conditions (up to 60 °C), and during loss of cooling/loss of coolant accidents (>100 °C)

A long pentraxin-3-derived pentapeptide for the therapy of FGF8b-driven steroid hormone-regulated cancers

Fibroblast growth factor-8b (FGF8b) affects the epithelial/stromal compartments of steroid hormone-regulated tumors by exerting an autocrine activity on cancer cells and a paracrine pro-angiogenic function, thus contributing to tumor progression. The FGF8b/FGF receptor (FGFR) system may therefore represent a target for the treatment of steroid hormone-regulated tumors. The soluble pattern recognition receptor long pentraxin-3 (PTX3) binds various FGFs, including FGF2 and FGF8b, thus inhibiting the angiogenic and tumorigenic activity of androgen-regulated tumor cells. Nevertheless, the complex/proteinaceous structure of PTX3 hampers its pharmacological exploitation. In this context, the acetylated pentapeptide Ac-ARPCA-NH2 (ARPCA), corresponding to the N-terminal amino acid sequence PTX3(100-104), was identified as a minimal FGF2-binding peptide able to antagonize the biological activity of FGF2. Here, we demonstrate that ARPCA binds FGF8b and inhibits its capacity to form FGFR1-mediated ternary complexes with heparan sulphate proteoglycans. As a FGF8b antagonist, ARPCA inhibits FGFR1 activation and signalling in endothelial cells, hampering the angiogenic activity exerted in vitro and in vivo by FGF8b. Also, ARPCA suppresses the angiogenic and tumorigenic potential of prototypic androgen/FGF8b-dependent Shionogi 115 mammary carcinoma cells and of androgen/FGF8b/FGF2-dependent TRAMP-C2 prostate cancer cells. In conclusion, ARPCA represents a novel FGF8b antagonist with translational implications for the therapy of steroid hormone-regulated tumor

Selection of Candidate Housekeeping Genes for Normalization in Human Postmortem Brain Samples

The most frequently used technique to study the expression profile of genes involved in common neurological disorders is quantitative real-time RT-PCR, which allows the indirect detection of very low amounts of selected mRNAs in tissue samples. Expression analysis by RT-qPCR requires an appropriate normalization to the expression level of genes characterized by a stable, constitutive transcription. However, the identification of a gene transcribed at a very stable level is difficult if not impossible, since significant fluctuations of the level of mRNA synthesis often accompanies changes of cell behavior. The aim of this study is to identify the most stable genes in postmortem human brain samples of patients affected by Alzheimer’s disease (AD) suitable as reference genes. The experiments analyzed 12 commonly used reference genes in brain samples from eight individuals with AD and seven controls. After a careful analysis of the results calculated by geNorm and NormFinder algorithms, we found that CYC1 and EIF4A2 are the best reference genes. We remark on the importance of the determination of the best reference genes for each sample to be analyzed and suggest a practical combination of reference genes to be used in the analysis of human postmortem samples

The inhibition of 45A ncRNA expression reduces tumor formation, affecting tumor nodules compactness and metastatic potential in neuroblastoma cells

open16noWe recently reported the in vitro over-expression of 45A, a RNA polymerase IIItranscribed non-coding (nc)RNA, that perturbs the intracellular content of FE65L1 affecting cell proliferation rate, short-term response to genotoxic stress, substrate adhesion capacity and, ultimately, increasing the tumorigenic potential of human neuroblastoma cells. In this work, to deeply explore the mechanism by which 45A ncRNA contributes to cancer development, we targeted in vitro and in vivo 45A levels by the stable overexpression of antisense 45A RNA. 45A downregulation leads to deep modifications of cytoskeleton organization, adhesion and migration of neuroblastoma cells. These effects are correlated with alterations in the expression of several genes including GTSE1 (G2 and S phaseexpressed- 1), a crucial regulator of tumor cell migration and metastatic potential. Interestingly, the downregulation of 45A ncRNA strongly affects the in vivo tumorigenic potential of SKNBE2 neuroblastoma cells, increasing tumor nodule compactness and reducing GTSE1 protein expression in a subcutaneous neuroblastoma mouse model. Moreover, intracardiac injection of neuroblastoma cells showed that downregulation of 45A ncRNA also influences tumor metastatic ability. In conclusion, our data highlight a key role of 45A ncRNA in cancer development and suggest that its modulation might represent a possible novel anticancer therapeutic approach.openPenna, Ilaria; Gigoni, Arianna; Costa, Delfina; Vella, Serena; Russo, Debora; Poggi, Alessandro; Villa, Federico; Brizzolara, Antonella; Canale, Claudio; Mescola, Andrea; Daga, Antonio; Russo, Claudio; Nizzari, Mario; Florio, Tullio; Menichini, Paola; Pagano, AldoPenna, Ilaria; Gigoni, Arianna; Costa, Delfina; Vella, SERENA LUISA; Russo, Debora; Poggi, Alessandro; Villa, Federico; Brizzolara, Antonella; Canale, Claudio; Mescola, Andrea; Daga, Antonio; Russo, Claudio; Nizzari, Mario; Florio, Tullio; Menichini, Paola; Pagano, Ald

Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00-0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00-0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02-0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics

Mercury DPM: fast, flexible particle simulations in complex geometries part II: applications

MercuryDPM is a particle-simulation software developed open-source by a global network of researchers. It was designed ​ab initio to simulate realistic geometries and materials, thus it contains several unique features not found in any other particle simulation software. These features have been discussed in a companion paper published in the DEM7 conference proceedings; here we present several challenging setups implemented in MercuryDPM ​ . Via these setups, we demonstrate the unique capability of the code to simulate and analyse highly complex geotechnical and industrial applications.These tups implemented include complex geometries such as (i) a screw conveyor, (ii) steady-state inflow conditions for chute flows, (iii) a confined conveyor belt to simulate a steady-state breaking wave, and(iii)aquasi-2D cylindrical slice to efficiently study shear flows.​MercuryDPM is also parallel, which we showcase via a multi-million particle simulations of a rotating drum. We further demonstrate how to simulate complex particle interactions, including: (i)deformable, charged clay particles; and (ii) liquid bridges and liquid migration in wet particulates, (iii) non-spherical particles implemented via superquadrics. Finally, we show how to analyse and complex systems using the unique micro-macro mapping (coarse-graining) tool MercuryCG