Model-based simulations of pulsed laser ablation using an embedded finite element method.

A model of thermal ablation with application to multi-pulsed laser lithotripsy is presented. The approach is based on a one-sided Stefan-Signorini model for thermal ablation, and relies on a level-set function to represent the moving interface between the solid phase and a fictitious gas phase (representing the ablated material). The model is discretized with an embedded finite element method, wherein the interface geometry can be arbitrarily located relative to the background mesh. Nitsche's method is adopted to impose the Signorini condition on the moving interface. A bound constraint is also imposed to deal with thermal shocks that can arise during representative simulations of pulsed ablation with high-power lasers. We report simulation results based on experiments for pulsed laser ablation of wet BegoStone samples treated in air, where Begostone has been used as a phantom material for kidney stone. The model is calibrated against experimental measurements by adjusting the percentage of incoming laser energy absorbed at the surface of the stone sample. Simulation results are then validated against experimental observations for the crater area, volume, and geometry as a function of laser pulse energy and duration. Our studies illustrate how the spreading of the laser beam from the laser fiber tip with concomitantly reduced incident laser irradiance on the damaged crater surface explains trends in both the experimental observations and the model-based simulation results.

Simultaneous determination and pharmacokinetic study of giraldoid a, giraldoid B in rat plasma after oral administration of Daphne giraldii Nitsche extracts by LC-MS/MS.

A simple sensitive LC-MS/MS method has been developed for the simultaneous determination of giraldoid A and giraldoid B in rat plasma. The method was applied to pharmacokinetics studies of the two compounds from Daphne giraldii Nitsche. Chromatographic separation was accomplished on an Acquity UPLC™ BEH C18 column (100 × 2.1 mm, 1.7 mm) by gradient elution with a flow rate of 0.2 mL min-1. The method was linear over the concentration range of 1.0-1000 ng mL-1 , and the lower limits of quantification were 1.04 ± 0.10 and 1.04 ± 0.09 ng mL-1 , respectively. The intra- and inter-day precisions (RSD) were <10.14 and 9.96%. The extraction recovery of the analytes was acceptable. Stability studies demonstrated that the two compounds were stable in the preparation and analytical process. The maximum plasma concentration was 687.78 ± 243.62 ng mL-1 for giraldoid A and 952.38 ± 131.99 ng mL-1 for giraldoid B. The time to reach the maximum plasma concentration was 0.50 ± 0.37 h for giraldoid A and 0.50 ± 0.66 h for giraldoid B. The validated method was successfully applied to investigate the concentration-time profiles of giraldoid A and giraldoid B.

An immersogeometric variational framework for fluid-structure interaction: application to bioprosthetic heart valves.

In this paper, we develop a geometrically flexible technique for computational fluid-structure interaction (FSI). The motivating application is the simulation of tri-leaflet bioprosthetic heart valve function over the complete cardiac cycle. Due to the complex motion of the heart valve leaflets, the fluid domain undergoes large deformations, including changes of topology. The proposed method directly analyzes a spline-based surface representation of the structure by immersing it into a non-boundary-fitted discretization of the surrounding fluid domain. This places our method within an emerging class of computational techniques that aim to capture geometry on non-boundary-fitted analysis meshes. We introduce the term "immersogeometric analysis" to identify this paradigm. The framework starts with an augmented Lagrangian formulation for FSI that enforces kinematic constraints with a combination of Lagrange multipliers and penalty forces. For immersed volumetric objects, we formally eliminate the multiplier field by substituting a fluid-structure interface traction, arriving at Nitsche's method for enforcing Dirichlet boundary conditions on object surfaces. For immersed thin shell structures modeled geometrically as surfaces, the tractions from opposite sides cancel due to the continuity of the background fluid solution space, leaving a penalty method. Application to a bioprosthetic heart valve, where there is a large pressure jump across the leaflets, reveals shortcomings of the penalty approach. To counteract steep pressure gradients through the structure without the conditioning problems that accompany strong penalty forces, we resurrect the Lagrange multiplier field. Further, since the fluid discretization is not tailored to the structure geometry, there is a significant error in the approximation of pressure discontinuities across the shell. This error becomes especially troublesome in residual-based stabilized methods for incompressible flow, leading to problematic compressibility at practical levels of refinement. We modify existing stabilized methods to improve performance. To evaluate the accuracy of the proposed methods, we test them on benchmark problems and compare the results with those of established boundary-fitted techniques. Finally, we simulate the coupling of the bioprosthetic heart valve and the surrounding blood flow under physiological conditions, demonstrating the effectiveness of the proposed techniques in practical computations.

Daphnes Cortex and its licorice-processed products suppress inflammation via the TLR4/NF-κB/NLRP3 signaling pathway and regulation of the metabolic profile in the treatment of rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Daphnes Cortex (Daphne Giraldii Nitsche, DGN) is a popular traditional Chinese herbal medicine for traumatic injuries and rheumatoid arthritis (RA) in the Shaanxi and Gansu provinces of China. Due to skin irritation caused by raw DGN (RDGN), licorice-processed DGN products are usually used in clinical practice. However, the efficacy and mechanisms of action between DGN and its licorice-processed DGN products in treating RA have not been compared. AIMS: This study compared the efficacy and elucidated the mechanisms in vitro and in vivo between RDGN and its licorice-processed DGN products in treating RA. MATERIALS AND METHODS: A collagen-induced RA rat model was established, and treated with different doses of RDGN and its licorice-processed DGN products for 4 weeks to explore the therapeutic effects. The anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). Analyses of the differential quality markers (DQMs) between DGN and its licorice-processed DGN products using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and non-targeted metabolomics analyses of rat synovial tissues were used to systematically explore correlations between DGN processing and its efficacy. RESULTS: Licorice-processed DGN products significantly ameliorated RA symptoms in CIA rats. Licorice-processed DGN products also regulated inflammatory cytokines, matrix metalloproteinases, and vascular endothelial growth factor in the serum and cell supernatants. Licorice-processed DGN products significantly inhibited Toll-like receptor 4/nuclear factor kappa B/NOD-like receptor family, pyrin domain containing 3 (TLR4/NF-κB/NLRP3) signaling in CIA rats and LPS-induced RAW264.7 cells. The DQMs between RDGN and its licorice-processed DGN products were identified, most of which were amino acids or energy-related metabolites present in licorice-processed DGN products. Correlations between DQMs with differential metabolites and differential metabolic pathways were established. CONCLUSIONS: Licorice-processed DGN products displayed better anti-inflammatory effects via the TLR4/NF-κB/NLRP3 signaling pathway on CIA rats and LPS-induced RAW264.7 cells, and regulation of the metabolic profile in treating RA.

Daphne giraldii Nitsche (Thymelaeaceae): Phytochemistry, pharmacology and medicinal uses.

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii.

Daphnegiravone D from Daphne giraldii Nitsche induces p38-dependent apoptosis via oxidative and nitrosative stress in hepatocellular carcinoma cells.

Daphnegiravone D (DGD), a prenylated flavonoid from Daphne giraldii Nitsche, significantly inhibited cell growth of several cancer cell lines without cytotoxicity on human normal cells. Our previous study showed that DGD could induce apoptosis in hepatocellular carcinoma Hep3B and HepG2 cells, but the detailed mechanism was still unclear. The present study provides that DGD-induced oxidative and nitrosative stress contribute to apoptotic cell death in Hep3B and HepG2 cells. Furthermore, there is a positive loop between oxidative stress and p38 activation, similar result is observed between nitrosative stress and p38. N-Acetylcysteine (NAC), a reactive oxygen species scavenger, could relieve DGD-induced oxidative stress, but exerts little effect on nitrosative stress. In addition, carboxy-PTIO (PTIO, a well-known scavenger of reactive nitrogen species) down-regulates the induction of nitrosative stress without obvious effect on oxidative stress in DGD-treated cells. In conclusion, the induction of oxidative and nitrosative stress could enhance p38-mediated apoptosis in DGD-treated Hep3B and HepG2 cells. Moreover, we speculated that OS and NS could not ultimately affect each other in DGD-treated HCC cells. This study gives a new insight on the mechanism of DGD-induced apoptotic cell death via oxidative and nitrosative stress in HCC cells.

Nitsche's Method For Helmholtz Problems with Embedded Interfaces.

In this work, we use Nitsche's formulation to weakly enforce kinematic constraints at an embedded interface in Helmholtz problems. Allowing embedded interfaces in a mesh provides significant ease for discretization, especially when material interfaces have complex geometries. We provide analytical results that establish the well-posedness of Helmholtz variational problems and convergence of the corresponding finite element discretizations when Nitsche's method is used to enforce kinematic constraints. As in the analysis of conventional Helmholtz problems, we show that the inf-sup constant remains positive provided that the Nitsche's stabilization parameter is judiciously chosen. We then apply our formulation to several 2D plane-wave examples that confirm our analytical findings. Doing so, we demonstrate the asymptotic convergence of the proposed method and show that numerical results are in accordance with the theoretical analysis.

An unstructured immersed finite element method for nonlinear solid mechanics.

We present an immersed finite element technique for boundary-value and interface problems from nonlinear solid mechanics. Its key features are the implicit representation of domain boundaries and interfaces, the use of Nitsche's method for the incorporation of boundary conditions, accurate numerical integration based on marching tetrahedrons and cut-element stabilisation by means of extrapolation. For discretisation structured and unstructured background meshes with Lagrange basis functions are considered. We show numerically and analytically that the introduced cut-element stabilisation technique provides an effective bound on the size of the Nitsche parameters and, in turn, leads to well-conditioned system matrices. In addition, we introduce a novel approach for representing and analysing geometries with sharp features (edges and corners) using an implicit geometry representation. This allows the computation of typical engineering parts composed of solid primitives without the need of boundary-fitted meshes.

Los 'fueguinos', Robert Lehmann-Nitsche y el estudio de los onas en la Exposición Nacional de Buenos Aires (1898) / 'Fueguinos', Robert Lehmann-Nitsche, and the study of the Ona at the Buenos Aires National Exhibit (1898)

Entre los primeros trabajos del antropólogo alemán Robert Lehmann-Nitsche como jefe del Departamento de Antropología del Museo de La Plata, Argentina, se cuentan las investigaciones sobre los habitantes de Tierra del Fuego, considerados como un 'relicto' evolutivo de la humanidad. Se repasa la importancia de las ferias y exposiciones como espacios de popularización científica y de 'trabajo de campo' para los estudiosos de fines del siglo XIX y principios del XX. Se examina la presentación de los 'fueguinos' en los espacios de las ferias y exposiciones europeas, los debates, los estudios realizados en Europa y el trabajo de Robert Lehmann-Nitsche en la Exposición Nacional de la Industria Argentina (Buenos Aires, 1898).

Among the first projects of German anthropologist Robert Lehmann-Nitsche as head of the Museum de La Plata's Department of Anthropology in Argentina was his research on the inhabitants of Tierra del Fuego, deemed evolutionary 'relics' of humanity. The article explores the role of shows and exhibits as spaces where science was popularized and where late nineteenth- and early twentieth-century scholars could do field work. The focus is on the presentation of 'fueguinos' at European shows and exhibits, debates, and studies, especially the work of Robert Lehmann-Nitsche at the National Exhibit of Argentinean Industry, held in Buenos Aires, 1898.