Tectonically undisturbed sedimentary rocks deposited in a quiescent shallow marine environment often include a sequence of strata that may present significant lithological variety at the scale of an ...engineering structure. Such rock masses exhibit engineering properties that are significantly different from tectonically disturbed rock masses of similar composition. For example, molasse consists of a series of tectonically undisturbed sediments of sandstones, conglomerates, siltstones and marls, produced by the erosion of mountain ranges after the final phase of an orogeny. They behave quite differently from flysch which has the same composition but which was tectonically disturbed during the orogeny. The molasses behave as continuous rock masses when they are confined at depth and the bedding planes do not appear as clearly defined discontinuity surfaces. Close to the surface the layering of the formations is discernible and only then similarities may exist with the structure of some types of flysch. Therefore extreme care is necessary in the use of geotechnical classification systems for the selection of design parameters, in order to avoid penalizing the rock mass unnecessarily. A discussion on the use of the geological strength index (GSI) for the characterisation of such rock masses is presented. Two GSI charts are proposed for estimating the mechanical properties of these masses: one mainly for tunnels; and the second for surface excavations. An example is given to illustrate the process of tunnel design in molassic rocks.
A dysregulated proinflammatory cytokine response is characteristic of severe coronavirus infections caused by SARS-CoV-2, yet our understanding of the underlying mechanism responsible for this ...imbalanced immune response remains incomplete. Processing bodies (PBs) are cytoplasmic membraneless ribonucleoprotein granules that control innate immune responses by mediating the constitutive decay or suppression of mRNA transcripts, including many that encode proinflammatory cytokines. PB formation promotes turnover or suppression of cytokine RNAs, whereas PB disassembly corresponds with the increased stability and/or translation of these cytokine RNAs. Many viruses cause PB disassembly, an event that can be viewed as a switch that rapidly relieves cytokine RNA repression and permits the infected cell to respond to viral infection. Prior to this submission, no information was known about how human coronaviruses (CoVs) impacted PBs. Here, we show SARS-CoV-2 and the common cold CoVs, OC43 and 229E, induced PB loss. We screened a SARS-CoV-2 gene library and identified that expression of the viral nucleocapsid (N) protein from SARS-CoV-2 was sufficient to mediate PB disassembly. RNA fluorescent in situ hybridization revealed that transcripts encoding TNF and IL-6 localized to PBs in control cells. PB loss correlated with the increased cytoplasmic localization of these transcripts in SARS-CoV-2 N protein-expressing cells. Ectopic expression of the N proteins from five other human coronaviruses (OC43, MERS, 229E, NL63 and SARS-CoV) did not cause significant PB disassembly, suggesting that this feature is unique to SARS-CoV-2 N protein. These data suggest that SARS-CoV-2-mediated PB disassembly contributes to the dysregulation of proinflammatory cytokine production observed during severe SARS-CoV-2 infection.
This paper investigates tunnel excavation through stratified rock masses from the engineering geological behaviour to the rock mass properties quantification and finally to the study of tunnel ...response, based on numerical analyses results. Initially the spectrum of the engineering geological behaviour of stratified rock masses in tunnelling is delimited and the critical failure mechanisms according to rock mass structure are described. Rock mass simulation as an equivalent isotropic geomaterial through the widely used characterisation systems in most cases cannot lead to a realistic prediction of the distribution and the values of total displacements. In addition, the complete and accurate simulation of all discontinuities networks involves high uncertainty. Therefore in the numerical analyses carried out, based on an already applied approach, the stratification planes, which contain less uncertainty than the secondary discontinuities and affect significantly the behaviour of tunnel, were simulated as separate elements and the rock mass parts between them as an isotropic material. Additionally, using simple rock mechanics principles, an approach for the quantification of the rock mass properties involved in the analyses is described, which tries to obtain the equivalence between the stratified rock mass and the sum of the distinct rock mass elements (stratification planes and internal rock mass). The numerical analyses depict the mechanism of convergence development in stratified rock masses and the differences between isotropic, anisotropic and transversally isotropic approaches are clearly demonstrated. Based on the results of the numerical analyses the incorporation of the stratification planes leads to an increase of the convergence mainly due to the bending of the rock mass strata where the stratification is tangential to the tunnel section. This increase depends on the GSI value of the reference rock mass and the discontinuities surface conditions.
► Engineering geological behaviour of stratified rock mass in tunnelling. ► The anisotropic tunnel convergence developed in stratified rock mass is examined. ► Numerical analyses by modelling discontinuities as a distinct element. ► Anisotropic analyses compared with isotropic and transversely isotropic. ► Methodology for the geotechnical parameters equivalence.
Amphibian skin is a mucosal surface in direct and continuous contact with a microbially diverse and laden aquatic and/or terrestrial environment. As such, frog skin is an important innate immune ...organ and first line of defence against pathogens in the environment. Critical to the innate immune functions of frog skin are the maintenance of physical, chemical, cellular, and microbiological barriers and the complex network of interactions that occur across all the barriers. Despite the global decline in amphibian populations, largely as a result of emerging infectious diseases, we understand little regarding the cellular and molecular mechanisms that underlie the innate immune function of amphibian skin and defence against pathogens. In this review, we discuss the structure, cell composition and cellular junctions that contribute to the skin physical barrier, the antimicrobial peptide arsenal that, in part, comprises the chemical barrier, the pattern recognition receptors involved in recognizing pathogens and initiating innate immune responses in the skin, and the contribution of commensal microbes on the skin to pathogen defence. We briefly discuss the influence of environmental abiotic factors (natural and anthropogenic) and pathogens on the immunocompetency of frog skin defences. Although some aspects of frog innate immunity, such as antimicrobial peptides are well-studied; other components and how they contribute to the skin innate immune barrier, are lacking. Elucidating the complex network of interactions occurring at the interface of the frog's external and internal environments will yield insight into the crucial role amphibian skin plays in host defence and the environmental factors leading to compromised barrier integrity, disease, and host mortality.
ABSTRACT
Cosmic rays (CRs) interact with the diffuse gas, radiation, and magnetic fields in the interstellar medium (ISM) to produce electromagnetic emissions that are a significant component of the ...all-sky flux across a broad wavelength range. The Fermi–Large Area Telescope (LAT) has measured these emissions at GeV γ-ray energies with high statistics. Meanwhile, the high-energy stereoscopic system (H.E.S.S.) telescope array has observed large-scale Galactic diffuse emission in the TeV γ-ray energy range. The emissions observed at GeV and TeV energies are connected by the common origin of the CR particles injected by the sources, but the energy dependence of the mixture from the general ISM (true ‘diffuse’), those emanating from the relatively nearby interstellar space about the sources, and the sources themselves, is not well understood. In this paper, we investigate predictions of the broad-band emissions using the galprop code over a grid of steady-state 3D models that include variations over CR sources, and other ISM target distributions. We compare, in particular, the model predictions in the very-high energy ( VHE; ≳100 GeV) γ-ray range with the H.E.S.S. Galactic plane survey (HGPS) after carefully subtracting emission from catalogued γ-ray sources. Accounting for the unresolved source contribution, and the systematic uncertainty of the HGPS, we find that the galprop model predictions agree with lower estimates for the HGPS source-subtracted diffuse flux. We discuss the implications of the modelling results for interpretation of data from the next generation Cherenkov Telescope Array (CTA).
Expanding Underground - Knowledge and Passion to Make a Positive Impact on the World contains the contributions presented at the ITA-AITES World Tunnel Congress 2023 (Athens, Greece, 12 – 18 May, ...2023). Tunnels and underground space are a predominant engineering practice that can provide sustainable, cost-efficient and environmentally friendly solutions to the ever-growing needs of modern societies. This underground expansion in more diverse and challenging infrastructure types or to novel underground uses can foster the changes needed. At the same time, the tunneling and underground space community needs to be better prepared and equipped with knowledge, tools and experience, to deal with the prevailing conditions, to successfully challenge and overcome adversities on this path. The papers in this book aim at contributing to the analysis of challenging conditions, the presentation and dissemination good practices, the introduction of new concepts, new tools and innovative elements that can help engineers and all stakeholders to reach their end goals. Expanding Underground - Knowledge and Passion to Make a Positive Impact on the World covers a wide range of aspects and topics related to the whole chain of the construction and operation of underground structures: Knowledge and Passion to Expand Underground for Sustainability and Resilience Geological, Geotechnical Site Investigation and Ground Characterization Planning and Designing of Tunnels and Underground Structures Mechanised Tunnelling and Microtunnelling Conventional Tunnelling, Drill-and-Blast Applications Tunnelling in Challenging Conditions - Case Histories and Lessons Learned Innovation, Robotics and Automation BIM, Big Data and Machine Learning Applications in Tunnelling Safety, Risk and Operation of Underground Infrastructure, and Contractual Practices, Insurance and Project Management The book is a must-have reference for all professionals and stakeholders involved in tunneling and underground space development projects.
Stress granules (SGs) are cytoplasmic condensates that often form as part of the cellular antiviral response. Despite the growing interest in understanding the interplay between SGs and other ...biological condensates and viral replication, the role of SG formation during coronavirus infection remains poorly understood. Several proteins from different coronaviruses have been shown to suppress SG formation upon overexpression, but there are only a handful of studies analyzing SG formation in coronavirus-infected cells. To better understand SG inhibition by coronaviruses, we analyzed SG formation during infection with the human common cold coronavirus OC43 (HCoV-OC43) and the pandemic SARS-CoV2. We did not observe SG induction in infected cells and both viruses inhibited eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and SG formation induced by exogenous stress. Furthermore, in SARS-CoV2 infected cells we observed a sharp decrease in the levels of SG-nucleating protein G3BP1. Ectopic overexpression of nucleocapsid (N) and non-structural protein 1 (Nsp1) from both HCoV-OC43 and SARS-CoV2 inhibited SG formation. The Nsp1 proteins of both viruses inhibited arsenite-induced eIF2α phosphorylation, and the Nsp1 of SARS-CoV2 alone was sufficient to cause a decrease in G3BP1 levels. This phenotype was dependent on the depletion of cytoplasmic mRNA mediated by Nsp1 and associated with nuclear accumulation of the SG-nucleating protein TIAR. To test the role of G3BP1 in coronavirus replication, we infected cells overexpressing EGFP-tagged G3BP1 with HCoV-OC43 and observed a significant decrease in virus replication compared to control cells expressing EGFP. The antiviral role of G3BP1 and the existence of multiple SG suppression mechanisms that are conserved between HCoV-OC43 and SARS-CoV2 suggest that SG formation may represent an important antiviral host defense that coronaviruses target to ensure efficient replication.
The paper presents the kinematics of rock instability of a high limestone promontory, where the Monemvasia historical site is situated, in Peloponnese in Southern Greece. The instability phenomena ...poses a significant threat to the town located at the base of the slope. Rockfall episodes occurred in the past due to the relaxation of the high cliff, whereas significant undermining of the castle frontiers has been observed at the slope crest. The predominant types of instability are of planar, wedge and toppling failure of medium to large blocks. In order to investigate the existing stability conditions and decide upon the protection measures, stability and rockfall analyses were carried out for numerous slope sections under different loading conditions and protection measures were suggested. A rock-fall risk rating system is proposed, which is based on morphological and structural criteria of the rock mass and on vulnerability and consequences. The rating system is applied for individual sections along the slope and a risk map was produced, which depicted areas having different degree of risk against rockfall occurrences.
Groundwater resources of karst aquifers within Circum-Mediterranean are a vital natural resource, which have been exploited since the dawn of the Mediterranean civilization. In Greece, carbonate ...formations are thought to be one of the most important sources for various water uses, that are vital for the country’s economy and development, that is agriculture and water supply. In most cases, they are considered as integral parts of some of the most strategic hydrosystems in Greece, containing surface water and groundwater resources that secure water supply for several anthropogenic activities. This paper provides a review of different aquifer types in Greece (granular and karstic), focusing on karst hydrosystems. It presents their spatial distribution throughout the entire Greek territory, and describes the most important environmental stresses upon them, while it analyzes their importance and role to the country’s water supply. Finally, this study analyzes the river basin of (Central Greece), used as a reference hydrosystem, to prove the ample importance of karst reservoirs in Greece.
There is an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases. Here, we report that thiopurines inhibit the replication of the betacoronaviruses HCoV-OC43 and ...SARS-CoV-2. 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. Overall, these findings suggest that small GTPases are promising targets for host-targeted antivirals.
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