Effect of Loading Rate and Time Delay on the Tangent Modulus Method (TMM) in Coal and Coal Measured Rocks

Non-destructive techniques of in-situ stress measurement from oriented cored rocks have great potential to be developed as a cost cost-efective and reliable alternative to the conventional overcoring and hydraulic fracturing methods. The tangent modulus method (TMM) is one such technique that can be applied to oriented cored rocks to measure in-situ stresses. Like the deformation rate analysis (DRA), the rock specimen is subjected to two cycles of uniaxial compression and the stresstangent modulus curve for the two cycles is obtained from the stress–strain curve. A bending point in the tangent modulus curve of the frst cycle is observed, separating it from the tangent modulus curve of the second cycle. The point of separation between the two curves is assumed to be the previously applied maximum stress. A number of experiments were conducted on coal and coal measured rocks (sandstone and limestone) to understand the efect of loading conditions and the time delay. The specimens were preloaded, and cyclic compressions were applied under three diferent modes of loading, four diferent strain rates, and time delays of up to one week. The bending point in the stress-tangent modulus curves occurred approximately at the applied pre-stress levels under all three loading modes, and no efect of loading rate was observed on the bending points in TMM. However, a clear efect of time delay was observed on the TMM, contradicting the DRA results. This could be due to the sensitivity of TMM and the range of its applicability, all of which need further investigation for the in-situ stress measurement.Zulfqar Ali, Murat Karakus, Giang D. Nguyen, Khalid Amrouc

Evaluation of the propensity of strain burst in brittle granite based on post-peak energy analysis

Available online 11 October 2019The increasing demand for resources and depletion of near ground mineral resources caused deeper mining operations under highstress rock mass conditions. As a result of this, strain burst, which is the sudden release of stored strain energy in the surrounding rock mass, has become more prevalent and created a considerable threat to workers and construction equipment. It is, therefore, imperative to understand how strain burst mechanism and stored excess strain energy are affected due to the high confinement in deep underground conditions. For this purpose, post-peak energy distributions for brittle rocks were investigated using a newly developed energy calculation method associated with acoustic emission (AE). A series of quasi-static uniaxial and triaxial compression tests controlled by the circumferential expansion was conducted. Snap-back behaviour known as Class-II behaviour associated with energy evolution and the material response under self-sustaining failure were analysed on granites under a wide range of confining pressures (0–60 MPa). The experimental results underline that the energy evolution characteristics are strongly linked to confinement. Stored elastic strain energy (dUE), energy consumed by dominating cohesion weakening (dUCW) and energy dissipated during mobilisation of frictional failure (dUFM) showed a rising trend as increasing the confining pressure. An intrinsic ejection velocity was proposed to express the propensity of strain burst that was purely determined by the excess strain energy released from Class II rock.Selahattin Akdag, Murat Karakus, Giang D. Nguyen, Abbas Taheri, Thomas Brunin

SARS-CoV-2 variants reveal features critical for replication in primary human cells

Since entering the human population, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; the causative agent of Coronavirus Disease 2019 [COVID-19]) has spread worldwide, causing >100 million infections and >2 million deaths. While large-scale sequencing efforts have identified numerous genetic variants in SARS-CoV-2 during its circulation, it remains largely unclear whether many of these changes impact adaptation, replication, or transmission of the virus. Here, we characterized 14 different low-passage replication-competent human SARS-CoV-2 isolates representing all major European clades observed during the first pandemic wave in early 2020. By integrating viral sequencing data from patient material, virus stocks, and passaging experiments, together with kinetic virus replication data from nonhuman Vero-CCL81 cells and primary differentiated human bronchial epithelial cells (BEpCs), we observed several SARS-CoV-2 features that associate with distinct phenotypes. Notably, naturally occurring variants in Orf3a (Q57H) and nsp2 (T85I) were associated with poor replication in Vero-CCL81 cells but not in BEpCs, while SARS-CoV-2 isolates expressing the Spike D614G variant generally exhibited enhanced replication abilities in BEpCs. Strikingly, low-passage Vero-derived stock preparation of 3 SARS-CoV-2 isolates selected for substitutions at positions 5/6 of E and were highly attenuated in BEpCs, revealing a key cell-specific function to this region. Rare isolate-specific deletions were also observed in the Spike furin cleavage site during Vero-CCL81 passage, but these were rapidly selected against in BEpCs, underscoring the importance of this site for SARS-CoV-2 replication in primary human cells. Overall, our study uncovers sequence features in SARS-CoV-2 variants that determine cell-specific replication and highlights the need to monitor SARS-CoV-2 stocks carefully when phenotyping newly emerging variants or potential variants of concern

Identification of the site of oxidase substrate binding in Scytalidium thermophilum catalase.

The catalase from Scytalidium thermophilum is a homotetramer containing a heme d in each active site. Although the enzyme has a classical monofunctional catalase fold, it also possesses oxidase activity towards a number of small organics, including catechol and phenol. In order to further investigate this, the crystal structure of the complex of the catalase with the classical catalase inhibitor 3-amino-1,2,4-triazole (3TR) was determined at 1.95 Å resolution. Surprisingly, no binding to the heme site was observed; instead, 3TR occupies a binding site corresponding to the NADPH-binding pocket in mammalian catalases at the entrance to a lateral channel leading to the heme. Kinetic analysis of site-directed mutants supports the assignment of this pocket as the binding site for oxidase substrates

IFITM3 incorporation sensitizes influenza A virus to antibody-mediated neutralization

The disease severity of influenza is highly variable in humans, and one genetic determinant behind these differences is the IFITM3 gene. As an effector of the interferon response, IFITM3 potently blocks cytosolic entry of influenza A virus (IAV). Here, we reveal a novel level of inhibition by IFITM3 in vivo: We show that incorporation of IFITM3 into IAV particles competes with incorporation of viral hemagglutinin (HA). Decreased virion HA levels did not reduce infectivity, suggesting that high HA density on IAV virions may be an antagonistic strategy used by the virus to prevent direct inhibition. However, we found that IFITM3-mediated reduction in HA content sensitizes IAV to antibody-mediated neutralization. Mathematical modeling predicted that this effect decreases and delays peak IAV titers, and we show that, indeed, IFITM3-mediated sensitization of IAV to antibody-mediated neutralization impacts infection outcome in an in vivo mouse model. Overall, our data describe a previously unappreciated interplay between the innate effector IFITM3 and the adaptive immune response

Computers in Secondary Schools: Educational Games

This entry introduces educational games in secondary schools. Educational games include three main types of educational activities with a playful learning intention supported by digital technologies: educational serious games, educational gamification, and learning through game creation. Educational serious games are digital games that support learning objectives. Gamification is defined as the use of "game design elements and game thinking in a non-gaming context" (Deterding et al. 2011, p. 13). Educational gamification is not developed through a digital game but includes game elements for supporting the learning objectives. Learning through game creation is focused on the process of designing and creating a prototype of a game to support a learning process related to the game creation process or the knowledge mobilized through the game creation process. Four modalities of educational games in secondary education are introduced in this entry to describe educational games in secondary education: educational purpose of entertainment games, serious games, gamification, and game design

microRNA 1307 Is a Potential Target for SARS-CoV-2 Infection: An in Vitro Model

microRNAs (miRs) are proposed as critical molecular targets in SARS-CoV-2 infection. Our recent in silico studies identified seven SARS-CoV-2 specific miR-like sequences, which are highly conserved with humans, including miR-1307-3p, with critical roles in COVID-19. In this current study, Vero cells were infected with SARS-CoV-2, and miR expression profiles were thereafter confirmed by qRT-PCR. miR-1307-3p was the most highly expressed miR in the infected cells; we, therefore, transiently inhibited its expression in both infected and uninfected cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay assessed cell viability following SARS-CoV-2 infection, identifying that miR-1307 expression is inversely correlated with cell viability. Lastly, changes in miR-1307-dependent pathways were analyzed through a detailed miRNOME and associated in silico analysis. In addition to our previously identified miRs, including miR-1307-3p, the upregulation of miR-193a-5p, miR-5100, and miR-23a-5p and downregulation of miR-130b-5p, miR34a-5p, miR-505-3p, miR181a-2-3p, miR-1271-5p, miR-598-3p, miR-34c-3p, and miR-129-5p were also established in Vero cells related to general lung disease-related genes following SARS-CoV-2 infection. Targeted anti-miR-1307-3p treatment rescued cell viability in infection when compared to SARS CoV-2 mediated cell cytotoxicity only. We furthermore identified by in silico analysis that miR-1307-3p is conserved in all SARS-CoV-2 sequences/strains, except in the BA.2 variant, possibly contributing to the lower disease severity of this variant, which warrants further investigation. Small RNA seq analysis was next used to evaluate alterations in the miRNOME, following miR-1307-3p manipulation, identifying critical pathobiological pathways linked to SARS-CoV-2 infection-mediated upregulation of this miR. On the basis of our findings, miRNAs like miR-1307-3p play a critical role in SARS-CoV-2 infection, including via effects on disease progression and severity

Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure.</p> <p>Methods</p> <p>A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay.</p> <p>Discussion</p> <p>The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure.</p> <p>Trial Registration</p> <p>Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01143909">NCT01143909</a></p