Dynamics of coupled and uncoupled two-phase flows in a slab mold

Two-phase flows in a mold of a slab caster are studied using water modeling, particle-image velocimetry (PIV), and computational fluid-dynamics techniques. Two-way coupled flows are observed in liquidgas systems, because both phases influence each other’s momentum transfer. In addition to this concept, PIV measurements indicate the existence of structurally coupled flows, where the velocity vectors of both phases observe similar orientations. When the drag forces of the liquid, exerted on the bubbles, exceed a certain value of the inertial forces of the liquid phase, at high mass loads of gas (ratio of mass flow rates of the gas phase and the liquid phase), the flow becomes structurally coupled. These types of flows promote large oscillations of the meniscus level. Two jets, liquid and bubble, were identified; the latter always reported larger angles than the first, independent of the gas load. Thus, a gas-rich jet is located closer to the lower edge of the submerged entry nozzle (SEN) port, and the liquid-rich jet is found above this position. The liquid-jet angle approaches that of the SEN port when the flow becomes structurally coupled. Structurally uncoupled flows report gas jets that follow torrent-type patterns which are well explained using a multiphase fluid-dynamics model. Structurally coupled flows yield gas jets with a continuous pattern.     

Residual stress-affected diffusion during plasma nitriding of tool steels

Plasma nitriding of tool materials is common practice to improve the wear resistance and lifetime of tools. Machining-induced compressive residual stresses in shallow layers of some tenths of microns are observed accompanied by other characteristic properties of machined surfaces in these high-strength materials. After plasma nitriding of M2 high-speed steel, previously induced compressive residual stresses remain stable and the depth of diffusion layers decreases with increasing compressive residual stresses. This article reports investigations of plasma nitrided samples with different levels of residual stresses induced prior to the nitriding process. For comparison, experiments with bending load stresses during plasma nitriding have also been carried out. The plasma nitriding treatment was performed at constant temperature of 500 °C with a gas mixture of 5 vol pct N₂ in hydrogen. Nitriding time was varied from 30 to 120 minutes. All samples were characterized before and after plasma nitriding concerning microstructure, roughness, microhardness, chemical composition, and residual stress states. Experimental results are compared with analytical calculations on (residual) stress effects in diffusion and show a clear effect of residual and load stresses in the diffusion of nitrogen in a high-strength M2 tool steel.     

The face of the patent is not the “Whole Story”: determining effective life of a pharmaceutical patent in the United States

This article provides an overview of the factors that may contribute to the effective term of protection for a pharmaceutical product in the USA––by patent and by FDA market exclusivities, identifies public and commercial sources for collecting relevant patent term and exclusivity data, and provides a strategy for ensuring that the effective term of protection has been calculated accurately.     

Modelling of Bird Strike on an Aircraft Wing Leading Edge Made from Fibre Metal Laminates – Part 2: Modelling of Impact with SPH Bird Model

Fibre Metal Laminates with layers of aluminium alloy and high strength glass fibre composite have been reported to possess excellent impact properties and be suitable for aircraft parts likely to be subjected to impacts such as runway debris or bird strikes. In a collaborative research project, aircraft wing leading edge structures with a glass-based FML skin have been designed, built, and subjected to bird strike tests that have been modelled with finite element analysis. In this second part of a two-part paper, a finite element model is developed for simulating the bird strike tests, using Smooth Particle Hydrodynamics (SPH) for modelling the bird and the material model developed in Part 1 of the paper for modelling the leading edge skin. The bird parameters are obtained from a system identification analysis of strikes on flat plates. Pre-test simulations correctly predicted that the bird did not penetrate the leading edge skin, and correctly forecast that one FML lay-up would deform more than the other. Post test simulations included a model of the structure supporting the test article, and the predicted loads transferred to the supporting structure were in good agreement with the experimental values. The SPH bird model showed no signs of instability and correctly modelled the break-up of the bird into particles. The rivets connecting the skin to the ribs were found to have a profound effect on the performance of the structure.     

Reaction of Corroles with Sarcosine and Paraformaldehyde: A New Facet of Corrole Chemistry

Details on the unexpected formation of two new (dimethylamino)methyl corrole isomers from the reaction of 5,10,15-tris(pentafluorophenyl)corrolatogallium(III) with sarcosine and paraformaldehyde are presented. Semi-empirical calculations on possible mechanism pathways seem to indicate that the new compounds are probably formed through a Mannich-type reaction. The extension of the protocol to the free-base 5,10,15-tris(pentafluorophenyl)corrole afforded an unexpected new seven-membered ring corrole derivative, confirming the peculiar behavior of corroles towards known reactions when compared to the well-behaved porphyrin counterparts.     

Nitric Oxide Metabolic Pathway in Drought-Stressed Nodules of Faba Bean (Vicia faba L.)

Drought is an environmental stress that strongly impacts plants. It affects all stages of growth and induces profound disturbances that influence all cellular functions. Legumes can establish a symbiosis with Rhizobium-type bacteria, whose function is to fix atmospheric nitrogen in organs called nodules and to meet plant nitrogen needs. Symbiotic nitrogen fixation (SNF) is particularly sensitive to drought. We raised the hypothesis that, in drought-stressed nodules, SNF inhibition is partly correlated to hypoxia resulting from nodule structure compaction and an increased O₂ diffusion barrier, and that the nodule energy regeneration involves phytoglobin–nitric oxide (Pgb–NO) respiration. To test this hypothesis, we subjected faba bean (Vicia faba L.) plants nodulated with a Rhizobium laguerreae strain to either drought or osmotic stress. We monitored the N₂-fixation activity, the energy state (ATP/ADP ratio), the expression of hypoxia marker genes (alcohol dehydrogenase and alanine aminotransferase), and the functioning of the Pgb–NO respiration in the nodules. The collected data confirmed our hypothesis and showed that (1) drought-stressed nodules were subject to more intense hypoxia than control nodules and (2) NO production increased and contributed via Pgb–NO respiration to the maintenance of the energy state of drought-stressed nodules.     

Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD)

Heart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of reperfusion or after a delay. An isolated rat heart model was used as a model of DCD. Hearts were submitted to a cardiac arrest of 40 min of global warm ischemia (37 °C) followed by 3 h of 4 °C-cold preservation, then 60 min reperfusion. Hearts were randomly allocated into the following groups: control, ischemic postconditioning (POST, consisting of two episodes each of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and CsA group (CsA was perfused at 250 nM for 10 min at reperfusion). In respective subgroups, POST and CsA were applied after a delay of 3, 10, and 20 min. Necrosis was lower in CsA and POST versus controls (p < 0.01) whereas heart functions were improved (p < 0.01). However, while the POST lost its efficacy if delayed beyond 3 min of reperfusion, CsA treatment surprisingly showed a reduction of necrosis even if applied after a delay of 3 and 10 min of reperfusion (p < 0.01). This cardioprotection by delayed CsA application correlated with better functional recovery and higher mitochondrial respiratory index. Furthermore, calcium overload necessary to induce mitochondrial permeability transition pore (MPTP) opening was similar in all cardioprotection groups, suggesting a crucial role of MPTP in this delayed protection of DCD hearts.     

Bioluminescence Production by Turnip Yellows Virus Infectious Clones: A New Way to Monitor Plant Virus Infection

We used the NanoLuc luciferase bioluminescent reporter system to detect turnip yellows virus (TuYV) in infected plants. For this, TuYV was genetically tagged by replacing the C-terminal part of the RT protein with full-length NanoLuc (TuYV-NL) or with the N-terminal domain of split NanoLuc (TuYV-N65-NL). Wild-type and recombinant viruses were agro-infiltrated in Nicotiana benthamiana, Montia perfoliata, and Arabidopsis thaliana. ELISA confirmed systemic infection and similar accumulation of the recombinant viruses in N. benthamiana and M. perfoliata but reduced systemic infection and lower accumulation in A. thaliana. RT-PCR analysis indicated that the recombinant sequences were stable in N. benthamiana and M. perfoliata but not in A. thaliana. Bioluminescence imaging detected TuYV-NL in inoculated and systemically infected leaves. For the detection of split NanoLuc, we constructed transgenic N. benthamiana plants expressing the C-terminal domain of split NanoLuc. Bioluminescence imaging of these plants after agro-infiltration with TuYV-N65-NL allowed the detection of the virus in systemically infected leaves. Taken together, our results show that NanoLuc luciferase can be used to monitor infection with TuYV.     

The SARS-CoV-2 Delta-Omicron Recombinant Lineage (XD) Exhibits Immune-Escape Properties Similar to the Omicron (BA.1) Variant

Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health. Here, using pseudotyped particles, we show that ACE2 binding and cell tropism of XD mimics that of BA.1. Further, XD and BA.1 displayed comparable sensitivity to neutralization by antibodies induced upon vaccination with BNT162b2/Comirnaty (BNT) or BNT vaccination followed by breakthrough infection. Our findings reveal important biological commonalities between XD and Omicron BA.1 host cell entry and its inhibition by antibodies.     

Identification of Potential New Aedes aegypti Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach

Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0^®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.