A cut finite element method for coupled bulk-surface problems on time-dependent domains

In this contribution we present a new computational method for coupled bulk-surface problems on time-dependent domains. The method is based on a space-time formulation using discontinuous piecewise linear elements in time and continuous piecewise linear elements in space on a fixed background mesh. The domain is represented using a piecewise linear level set function on the background mesh and a cut finite element method is used to discretize the bulk and surface problems. In the cut finite element method the bilinear forms associated with the weak formulation of the problem are directly evaluated on the bulk domain and the surface defined by the level set, essentially using the restrictions of the piecewise linear functions to the computational domain. In addition a stabilization term is added to stabilize convection as well as the resulting algebraic system that is solved in each time step. We show in numerical examples that the resulting method is accurate and stable and results in well conditioned algebraic systems independent of the position of the interface relative to the background mesh

Full Gradient Stabilized Cut Finite Element Methods for Surface Partial Differential Equations

We propose and analyze a new stabilized cut finite element method for the Laplace-Beltrami operator on a closed surface. The new stabilization term provides control of the full $\mathbb{R}^3$ gradient on the active mesh consisting of the elements that intersect the surface. Compared to face stabilization, based on controlling the jumps in the normal gradient across faces between elements in the active mesh, the full gradient stabilization is easier to implement and does not significantly increase the number of nonzero elements in the mass and stiffness matrices. The full gradient stabilization term may be combined with a variational formulation of the Laplace-Beltrami operator based on tangential or full gradients and we present a simple and unified analysis that covers both cases. The full gradient stabilization term gives rise to a consistency error which, however, is of optimal order for piecewise linear elements, and we obtain optimal order a priori error estimates in the energy and $L^2$ norms as well as an optimal bound of the condition number. Finally, we present detailed numerical examples where we in particular study the sensitivity of the condition number and error on the stabilization parameter.Comment: 20 pages, 4 figures, 5 tables. arXiv admin note: text overlap with arXiv:1507.0583

Mitochondrial Stress Response in Neural Stem Cells Exposed to Electronic Cigarettes.

Stem cells provide a sensitive model to study exposure to toxicants, such as cigarette smoke. Electronic cigarettes (ECs) are popular nicotine delivery devices, often targeted to youth and pregnant mothers. However, little is known about how chemicals in ECs might affect neural stem cells, and in particular their mitochondria, organelles that maintain cell functionality and health. Here we show that the mechanism underlying EC-induced stem cell toxicity is stress-induced mitochondrial hyperfusion (SIMH), a transient survival response accompanied by increased mitochondrial oxidative stress. We identify SIMH as a survival response to nicotine, now widely available in EC refill fluids and in pure form for do-it-yourself EC products. These observed mitochondrial alterations combined with autophagy dysfunction to clear damaged mitochondria could lead to faulty stem cell populations, accelerate cellular aging, and lead to acquired mitochondriopathies. Any nicotine-containing product may likewise stress stem cells with long-term repercussions for users and passively exposed individuals. VIDEO ABSTRACT

Divergence-free cut finite element methods for Stokes flow

We develop two unfitted finite element methods for the Stokes equations based on $\mathbf{H}^{\text{div}}$-conforming finite elements. The first method is a cut finite element discretization of the Stokes equations based on the Brezzi-Douglas-Marini elements and involves interior penalty terms to enforce tangential continuity of the velocity at interior edges in the mesh. The second method is a cut finite element discretization of a three-field formulation of the Stokes problem involving the vorticity, velocity, and pressure and uses the Raviart-Thomas space for the velocity. We present mixed ghost penalty stabilization terms for both methods so that the resulting discrete problems are stable and the divergence-free property of the $\mathbf{H}^{\text{div}}$-conforming elements is preserved also for unfitted meshes. We compare the two methods numerically. Both methods exhibit robust discrete problems, optimal convergence order for the velocity, and pointwise divergence-free velocity fields, independently of the position of the boundary relative to the computational mesh

NF-Kβ Activation in U266 Cells on Mesenchymal Stem Cells

Purpose: Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy. This study examined the relationship between U266 cells and MSCs. Methods: U266 cells were cultured with Umbilical Cord Blood derived-MSCs (UCB-MSCs) and Conditioned Medium (C.M). Effect of UCB-MSCs and C.M on proliferation rate and CD54 expression of U266 cells were examined with MTT assay and Flowcytometry respectively. Furthermore, expression of CXCL1, PECAM-1, JUNB, CCL2, CD44, CCL4, IL-6, and IL-8 were analyzed by Real Time-PCR (RT-PCR). Moreover, status of p65 protein in NF-kβ pathway assessed by western blotting. Results: Our findings confirm that UCB-MSCs support U266 cells proliferation and they increase CD54 expression. In addition, we demonstrate that UCB-MSCs alter the expression of CCL4, IL-6, IL-8, CXCL1 and the levels of phosphorylated p65 in U266 cells.Conclusion: Our study provides a novel sight to the role of MSCs in the activation of NF-kβ signaling pathway. So, NF-kβ signaling pathway will be targeted in future therapies against MM

Assessment of a Large-Scale Unbiased Malignant Pleural Effusion Proteomics Study of a Real-Life Cohort

Funding Information: R.M. is supported by Fundação para a Ciência e a Tecnologia (CEEC position, 2019–2025 investigator). This article is a result of the projects (iNOVA4Health—UIDB/04462/2020), supported by Lisboa Portugal Regional Operational Programme (Lisboa2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work is also funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT—Portuguese Foundation for Science and Technology under the projects number PTDC/BTM-TEC/30087/2017 and PTDC/BTM-TEC/30088/2017. Publisher Copyright: © 2022 by the authors.Background: Pleural effusion (PE) is common in advanced-stage lung cancer patients and is related to poor prognosis. Identification of cancer cells is the standard method for the diagnosis of a malignant PE (MPE). However, it only has moderate sensitivity. Thus, more sensitive diagnostic tools are urgently needed. Methods: The present study aimed to discover potential protein targets to distinguish malignant pleural effusion (MPE) from other non-malignant pathologies. We have collected PE from 97 patients to explore PE proteomes by applying state-of-the-art liquid chromatography-mass spectrometry (LC-MS) to identify potential biomarkers that correlate with immunohistochemistry assessment of tumor biopsy or with survival data. Functional analyses were performed to elucidate functional differences in PE proteins in malignant and benign samples. Results were integrated into a clinical risk prediction model to identify likely malignant cases. Sensitivity, specificity, and negative predictive value were calculated. Results: In total, 1689 individual proteins were identified by MS-based proteomics analysis of the 97 PE samples, of which 35 were diagnosed as malignant. A comparison between MPE and benign PE (BPE) identified 58 differential regulated proteins after correction of the p-values for multiple testing. Furthermore, functional analysis revealed an up-regulation of matrix intermediate filaments and cellular movement-related proteins. Additionally, gene ontology analysis identified the involvement of metabolic pathways such as glycolysis/gluconeogenesis, pyruvate metabolism and cysteine and methionine metabolism. Conclusion: This study demonstrated a partial least squares regression model with an area under the curve of 98 and an accuracy of 0.92 when evaluated on the holdout test data set. Furthermore, highly significant survival markers were identified (e.g., PSME1 with a log-rank of 1.68 × 10−6).publishersversionpublishe