Investigating the Inhibitory Properties of Cupressus sempervirens Extract against Copper Corrosion in 0.5 M H2SO4: Combining Quantum (Density Functional Theory Calculation-Monte Carlo Simulation) and Electrochemical-Surface Studies.

The study investigates the potential of Cupressus sempervirens (EO) as a sustainable and eco-friendly inhibitor of copper corrosion in a 0.5 M sulfuric acid medium. The electrochemical impedance spectroscopy analysis shows that the effectiveness of corrosion inhibition rises with increasing inhibitor concentrations, reaching 94% with the application of 2 g/L of EO, and potentiodynamic polarization (PDP) studies reveal that EO functions as a mixed-type corrosion inhibitor. In addition, the Langmuir adsorption isotherm is an effective descriptor of its adsorption. Scanning electron microscopy/energy-dispersive X-ray spectroscopy, atomic force microscopy surface examination, and contact angle measurement indicate that EO may form a barrier layer on the metal surface. Density functional theory calculations, Monte Carlo simulation models, and the radial distribution function were also used to provide a more detailed understanding of the corrosion protection mechanism. Overall, the findings suggest that Cupressus sempervirens (EO) has the potential to serve as an effective and sustainable corrosion inhibitor for copper in a sulfuric acid medium, contributing to the development of green corrosion inhibitors for environmentally friendly industrial processes.

Seeking an optimal dosing regimen for OZ439/DSM265 combination therapy for treating uncomplicated falciparum malaria.

BACKGROUND: The efficacy of artemisinin-based combination therapies (ACTs), the first-line treatments for uncomplicated falciparum malaria, has been declining in malaria-endemic countries due to the emergence of malaria parasites resistant to these compounds. Novel alternative therapies are needed urgently to prevent the likely surge in morbidity and mortality due to failing ACTs. OBJECTIVES: This study investigates the efficacy of the combination of two novel drugs, OZ439 and DSM265, using a biologically informed within-host mathematical model. METHODS: A within-host model was developed, which accounts for the differential killing of these compounds against different stages of the parasite's life cycle and accommodates the pharmacodynamic interaction between the drugs. Data of healthy volunteers infected with falciparum malaria collected from four trials (three that administered OZ439 and DSM265 alone, and the fourth a combination of OZ439 and DSM265) were analysed. Model parameters were estimated in a hierarchical Bayesian framework. RESULTS: The posterior predictive simulations of our model predicted that 800 mg of OZ439 combined with 450 mg of DSM265, which are within the safe and tolerable dose range, can provide above 90% cure rates 42 days after drug administration. CONCLUSIONS: Our results show that the combination of OZ439 and DSM265 can be a promising alternative to replace ACTs. Our model can be used to inform future Phase 2 and 3 clinical trials of OZ439/DSM265, fast-tracking the deployment of this combination therapy in the regions where ACTs are failing. The dosing regimens that are shown to be efficacious and within safe and tolerable limits are suggested for future investigations.

Parasite-Host Dynamics throughout Antimalarial Drug Development Stages Complicate the Translation of Parasite Clearance.

Ensuring continued success against malaria depends on a pipeline of new antimalarials. Antimalarial drug development utilizes preclinical murine and experimental human malaria infection studies to evaluate drug efficacy. A sequential approach is typically adapted, with results from each stage informing the design of the next stage of development. The validity of this approach depends on confidence that results from murine malarial studies predict the outcome of clinical trials in humans. Parasite clearance rates following treatment are key parameters of drug efficacy. To investigate the validity of forward predictions, we developed a suite of mathematical models to capture parasite growth and drug clearance along the drug development pathway and estimated parasite clearance rates. When comparing the three infection experiments, we identified different relationships of parasite clearance with dose and different maximum parasite clearance rates. In Plasmodium berghei-NMRI mouse infections, we estimated a maximum parasite clearance rate of 0.2 (1/h); in Plasmodium falciparum-SCID mouse infections, 0.05 (1/h); and in human volunteer infection studies with P. falciparum, we found a maximum parasite clearance rate of 0.12 (1/h) and 0.18 (1/h) after treatment with OZ439 and MMV048, respectively. Sensitivity analysis revealed that host-parasite driven processes account for up to 25% of variance in parasite clearance for medium-high doses of antimalarials. Although there are limitations in translating parasite clearance rates across these experiments, they provide insight into characterizing key parameters of drug action and dose response and assist in decision-making regarding dosage for further drug development.

Modeling the Effect of Primary and Secondary Twinning on Texture Evolution during Severe Plastic Deformation of a Twinning-Induced Plasticity Steel.

Modeling the effect of deformation twinning and the ensuing twin-twin- and slip-twin-induced hardening is a long-standing problem in computational mechanical metallurgy of materials that deform by both slip and twinning. In this work, we address this effect using the twin volume transfer method, which obviates the need of any cumbersome criterion for twin variant selection. Additionally, this method is capable of capturing, at the same time, secondary or double twinning, which is particularly important for modeling in large strain regimes. We validate our modeling methodology by simulating the behavior of an Fe-23Mn-1.5Al-0.3C twinning-induced plasticity (TWIP) steel under large strain conditions, experimentally achieved in this work through equal-channel angular pressing (ECAP) for up to two passes in a 90° die following route BC at 300 °C. Each possible twin variant, whether nucleating inside the parent grain or inside a potential primary twin variant was predefined in the initial list of orientations as possible grain of the polycrystal with zero initial volume fraction. A novelty of our approach is to take into account the loss of coherency of the twins with their parent matrix under large strains, obstructing progressively their further growth. This effect has been captured by attenuating growth rates of twins as a function of their rotation away from their perfect twin orientation, dubbed here as "disorientation" with respect to the mother grain's lattice. The simulated textures and the hardening under tensile strain showed very good agreement with experimental characterization and mechanical testing results. Furthermore, upper-bound Taylor deformation was found to be operational for the TWIP steel deformation when all the above ingredients of twinning are captured, indicating that self-consistent schemes can be bypassed.

The bio-physics of condensation of divalent cations into the bacterial wall has implications for growth of Gram-positive bacteria.

BACKGROUND: The anionic-polyelectrolyte nature of the wall of Gram-positive bacteria has long been suspected to be involved in homeostasis of essential cations and bacterial growth. A better understanding of the coupling between the biophysics and the biology of the wall is essential to understand some key features at play in ion-homeostasis in this living system. METHODS: We consider the wall as a polyelectrolyte gel and balance the long-range electrostatic repulsion within this structure against the penalty entropy required to condense cations around wall polyelectrolytes. The resulting equations define how cations interact physically with the wall and the characteristic time required for a cation to leave the wall and enter into the bacterium to enable its usage for bacterial metabolism and growth. RESULTS: The model was challenged against experimental data regarding growth of Gram-positive bacteria in the presence of varying concentration of divalent ions. The model explains qualitatively and quantitatively how divalent cations interact with the wall as well as how the biophysical properties of the wall impact on bacterial growth (in particular the initiation of bacterial growth). CONCLUSION: The interplay between polymer biophysics and the biology of Gram positive bacteria is defined for the first time as a new set of variables that contribute to the kinetics of bacterial growth. GENERAL SIGNIFICANCE: Providing an understanding of how bacteria capture essential metal cations in way that does not follow usual binding laws has implications when considering the control of such organisms and their ability to survive and grow in extreme environments.

Hydrogel fibers for ACL prosthesis: design and mechanical evaluation of PVA and PVA/UHMWPE fiber constructs.

Prosthetic devices for anterior cruciate ligament (ACL) reconstruction have been unsuccessful due to mechanical failure or chronic inflammation. Polymer hydrogels combine biocompatibility and unique low friction properties; however, their prior use for ligament reconstruction has been restricted to coatings due to insufficient tensile mechanics. Here, we investigate new constructs of polyvinyl alcohol (PVA) hydrogel fibers. In water, these fibers swell to an equilibrium water content of 50% by weight, retaining a tensile modulus greater than 40 MPa along the fiber axis at low strain. Rope constructs were assembled for ACL replacement and mechanical properties were compared with data from the literature. Pure PVA hydrogel constructs closely reproduce the non-linear tensile stiffness of the native ACL with an ultimate strength of about 2000 N. An additional safety factor in tensile strength was achieved with composite braids by adding ultrahigh molecular weight polyethylene (UHMWPE) fibers around a core of PVA cords. Composition and braiding angle are adjusted to produce a non-linear tensile behavior within the range of the native ligament that can be predicted by a simple rope model. This design was found to sustain over one million cycles between 50 and 450 N with limited damage and less than 20% creep. The promising mechanical performances of these systems provide justification for more extensive in vivo evaluation.

Low bone mineral density is related to atherosclerosis in postmenopausal Moroccan women.

BACKGROUND: Some studies have implicated several possible metabolic linkages between osteoporosis and vascular calcification, including estrogen deficiency, vitamin D excess, vitamin K deficiency and lipid oxidation products. Nevertheless, it remains unclear whether osteoporosis and atherosclerosis are related to each other or are independent processes, both related to aging. The aim of this cross-sectional study was to evaluate the correlation between arterial thickening and bone status in a sample of apparently healthy Moroccan women. METHODS: Seventy-two postmenopausal women were studied. All patients were without secondary causes that might affect bone density. Bone status was assessed by bone mineral density (BMD) in lumbar spine and all femoral sites. Arterial wall thickening was assessed by intima-media thickness (IMT) in carotid artery (CA) and femoral artery (FA). Prevalent plaques were categorized into four groups ranging from low echogenicity to high echogenicity. RESULTS: The mean age was 59.2 +/- 8.3 years. 84.7% had at least one plaque. By Spearman Rank correlation, CA IMT was negatively correlated to Femoral total BMD (r = -0.33), Femoral neck BMD (r = -0.23), Ward triangle BMD (r = -0.30) and Trochanter BMD (r = -0.28) while there was no association with lumbar BMD. In multiple regression analysis, CA IMT emerged as an independent factor significantly associated with all femoral sites BMD after adjusting of confounding factors. FA IMT failed to be significantly associated with both Femoral and Lumbar BMD. No significant differences between echogenic, predominantly echogenic, predominantly echolucent and echolucent plaques groups were found concerning lumbar BMD and all femoral sites BMD CONCLUSION: Our results demonstrate a negative correlation between bone mineral density (BMD) qnd carotid intima-media thickness (IMT) in postmenopausal women, independently of confounding factors. We suggest that bone status should be evaluated in patients with vascular disease to assess whether preventive or therapeutic intervention is necessarry.

Micromechanical modeling of viscoelastic voided composites in the low-frequency approximation.

The self-consistent model of Cherkaoui et al. [J. Eng. Mater. Technol. 116, 274-278 (1994)] is used to compute the effective material moduli of a viscoelastic material containing coated spherical inclusions. Losses are taken into account by introducing the frequency-dependent, complex shear modulus of the viscoelastic matrix. Mode conversion appears through the localization tensors that govern the micromechanical behavior near the inclusions. The results are compared with the scattering model and the data of Baird et al. [J. Acoust. Soc. Am. 105, 1527-1538 (1999)]. The two models are in good agreement. The advantage of the self-consistent model is that it is applicable to the case of nonspherical inclusions embedded in anisotropic materials.