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

Meta-Analysis of MS-Based Proteomics Studies Indicates Interferon Regulatory Factor 4 and Nucleobindin1 as Potential Prognostic and Drug Resistance Biomarkers in Diffuse Large B Cell Lymphoma

Funding: Rune Matthiesen is supported by Fundação para a Ciência e a Tecnologia (CEEC position, 2019–2025 investigator). This article is a Fiigureresult 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 project numbers: PTDC/BTM-TEC/30087/2017 and PTDC/BTM-TEC/30088/2017.The prognosis of diffuse large B cell lymphoma (DLBCL) is inaccurately predicted using clinical features and immunohistochemistry (IHC) algorithms. Nomination of a panel of molecules as the target for therapy and predicting prognosis in DLBCL is challenging because of the divergences in the results of molecular studies. Mass spectrometry (MS)-based proteomics in the clinic represents an analytical tool with the potential to improve DLBCL diagnosis and prognosis. Previous proteomics studies using MS-based proteomics identified a wide range of proteins. To achieve a consensus, we reviewed MS-based proteomics studies and extracted the most consistently significantly dysregulated proteins. These proteins were then further explored by analyzing data from other omics fields. Among all significantly regulated proteins, interferon regulatory factor 4 (IRF4) was identified as a potential target by proteomics, genomics, and IHC. Moreover, annexinA5 (ANXA5) and nucleobindin1 (NUCB1) were two of the most up-regulated proteins identified in MS studies. Functional enrichment analysis identified the light zone reactions of the germinal center (LZ-GC) together with cytoskeleton locomotion functions as enriched based on consistent, significantly dysregulated proteins. In this study, we suggest IRF4 and NUCB1 proteins as potential biomarkers that deserve further investigation in the field of DLBCL sub-classification and prognosis.publishersversionpublishe