| 1. |
- Mark, Andreas, 1980, et al.
(författare)
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Microstructure Simulation of Early Paper Forming Using Immersed Boundary Methods
- 2011
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Ingår i: Paper360. - 1933-3684. ; 10:11, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Paper forming is the first step in the paper machine where a fibersuspension leaves the headbox and flows through a forming fabric.Complex physical phenomena occur during paper forming due to theinteraction between fibers, fillers and fines as well as chemicalsadded to the suspension. Understanding this process is important forthe development of improved paper products because the configurationof the fibers during this step has a large influence on the finalpaper quality. Since the effective paper properties depend on themicro-structure of the fiber web, a continuum model is inadequate andthe properties of each fiber need to be accounted for in thesimulations.In the present work, a framework for microstructure simulation ofearly paper forming has been developed. The simulation frameworkincludes a Navier-Stokes solver and immersed boundary methods are usedto resolve the flow around the fibers. The fibers are modeled with afinite element discretization of the Euler-Bernoulli beam equation ina co-rotational formulation. The contact model is based on a penaltymethod and includes friction as well as elastic and inelasticcollisions.The fiber model and the contact model are validated against demandingtest cases from the literature with excellent results. Thefluid-structure interaction in the model is examined by simulating anelastic beam oscillating in a cross flow. Finally, a simulation ofearly paper forming is performed to demonstrate the potential of theproposed framework. The unique modeling approach can be used toincrease the fundamental understanding of paper forming and supportprocess optimization.
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| 2. |
- Mark, Andreas, 1980, et al.
(författare)
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Microstructure Simulation of Early Paper Forming Using Immersed Boundary Methods
- 2011
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Ingår i: Progress in Paper Physics Seminar. - 9783851251630 ; , s. 283-290
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Konferensbidrag (refereegranskat)abstract
- Paper forming is the first step in the paper machinewhere a fiber suspension leaves the headbox and flowsthrough a forming fabric. Understanding this processis important for the development of improved paperproducts because the configuration of the fibers duringthis step has a large influence on the final paperquality.The simulation framework includes IBOFlow, a stateof-the-art Navier-Stokes solver, and PaperGeo, the virtualpaper structure generator in GeoDict. ImmersedBoundary Methods are used to resolve the flow aroundthe fibers. The fibers are modeled with a finite elementdiscretization of the Euler-Bernoulli beam equationin a co-rotational formulation. The contact modelis based on a penalty method and includes friction aswell as elastic and inelastic collisions.The fiber model and the contact model are validatedagainst demanding test problems from the literaturewith excellent result. The fluid-structure interaction inthe model is examined by simulating an elastic beamoscillating in a cross flow. Finally, a simulation of initialpaper forming is performed, which demonstratesthe capabilities of the simulation framework.
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| 3. |
- Svenning, Erik, 1986, et al.
(författare)
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Multiphase Simulation of Fiber Suspension Flows Using Immersed Boundary Methods
- 2012
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Ingår i: Nordic Pulp and Paper Research Journal. - 2000-0669 .- 0283-2631. ; 27:2, s. 184-191
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Tidskriftsartikel (refereegranskat)abstract
- Fiber suspension simulations are challenging since they involve transient fluid flow with immersed solid objects subject to large displacements and rotations. In the present work, a beam model in co-rotational formulation is coupled with a fluid solver using immersed boundary methods. The model is used to simulate a fiber in a shear flow and excellent agreement is found with Jeffery's equations. The shapes of fibers deforming in a shear flow are found to be in qualitative agreement with shapes observed in experiments.The flow of a fiber suspension is studied by simulating early paper forming with one-way and semi-two-way coupling. It is found that the flow through the fiber web needs to be resolved in order to predict the retention of fibers in the fiber web.
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| 4. |
- Andrä, Heiko, et al.
(författare)
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Micromechanical network model for the evaluation of quality controls of paper
- 2011
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Ingår i: Progress in Paper Physics Seminar. - 9783851251630 ; , s. 49-55
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Konferensbidrag (refereegranskat)abstract
- In this paper, we discuss the challenges in modelling and simulating infinitesimal and large deformations of cellulose fiber networks, mainly in the context of the prediction of quality controls for paper.Understanding the influence and sensitivity of macroscopic production parameters like grammage and thickness of paperboard and understanding the influence of the fiber suspension on the quality of paper is important for the development of better papers and for preserving raw materials and energy.The new simulation framework consists of the virtual stochastic paper structure generator PaperGeo, that was integrated in the GeoDict 1 software suite, and the finite element solver FeelMath (Finite Elements for Elastic Materials and Homogenization) for solving the equations of elasticity. The fibers and the contacts are modelled by using geometrically exact beams of Simo-type [1].The microstructural model and the fiber network model are validated against standard measurements of existing papers in the following way: At first we perform tensile and bending tests to measure the macroscopic stress-strain relations. In the next step we apply a representative macroscopic stress or strain onto the boundaries of realizations of the stochastic fiber network model and compute by homogenization the effective (stiffness) coefficients. Finally we compare the numerical results with the measurements.This procedure can also be used for an identification of elastic parameters on the microscale and to study the sensitivity of the effective (macroscopic) stiffness with regard to the parameters of the microstructure
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| 5. |
- Cifani, Paolo, et al.
(författare)
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Hunting for Protein Markers of Hypoxia by Combining Plasma Membrane Enrichment with a New Approach to Membrane Protein Analysis
- 2011
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 10:4, s. 1645-1656
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Tidskriftsartikel (refereegranskat)abstract
- Nontransient hypoxia is strongly associated with malignant lesions, resulting in aggressive behavior and resistance to treatment. We present an analysis of mRNA and protein expression changes in neuroblastoma cell lines occurring upon the transition from normoxia to hypoxia. The correlation between mRNA and protein level changes was poor, although some known hypoxia-driven genes and proteins correlated well. We present previously undescribed membrane proteins expressed under hypoxic conditions that are candidates for evaluation as biomarkers.
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| 6. |
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| 7. |
- Fredlund, Erik, et al.
(författare)
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The gene expression landscape of breast cancer is shaped by tumor protein p53 status and epithelial-mesenchymal transition
- 2012
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Gene expression data derived from clinical cancer specimens provide an opportunity to characterize cancer-specific transcriptional programs. Here, we present an analysis delineating a correlation-based gene expression landscape of breast cancer that identifies modules with strong associations to breast cancer-specific and general tumor biology. Methods: Modules of highly connected genes were extracted from a gene co-expression network that was constructed based on Pearson correlation, and module activities were then calculated using a pathway activity score. Functional annotations of modules were experimentally validated with an siRNA cell spot microarray system using the KPL-4 breast cancer cell line, and by using gene expression data from functional studies. Modules were derived using gene expression data representing 1,608 breast cancer samples and validated in data sets representing 971 independent breast cancer samples as well as 1,231 samples from other cancer forms. Results: The initial co-expression network analysis resulted in the characterization of eight tightly regulated gene modules. Cell cycle genes were divided into two transcriptional programs, and experimental validation using an siRNA screen showed different functional roles for these programs during proliferation. The division of the two programs was found to act as a marker for tumor protein p53 (TP53) gene status in luminal breast cancer, with the two programs being separated only in luminal tumors with functional p53 (encoded by TP53). Moreover, a module containing fibroblast and stroma-related genes was highly expressed in fibroblasts, but was also up-regulated by overexpression of epithelial-mesenchymal transition factors such as transforming growth factor beta 1 (TGF-beta1) and Snail in immortalized human mammary epithelial cells. Strikingly, the stroma transcriptional program related to less malignant tumors for luminal disease and aggressive lymph node positive disease among basal-like tumors. Conclusions: We have derived a robust gene expression landscape of breast cancer that reflects known subtypes as well as heterogeneity within these subtypes. By applying the modules to TP53-mutated samples we shed light on the biological consequences of non-functional p53 in otherwise low-proliferating luminal breast cancer. Furthermore, as in the case of the stroma module, we show that the biological and clinical interpretation of a set of co-regulated genes is subtype-dependent.
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| 8. |
- Kasza, Z., et al.
(författare)
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MicroRNA-24 Suppression of N-Deacetylase/N-Sulfotransferase-1 (NDST1) Reduces Endothelial Cell Responsiveness to Vascular Endothelial Growth Factor A (VEGFA)
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:36, s. 25956-25963
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) proteoglycans, present at the plasma membrane of vascular endothelial cells, bind to the angiogenic growth factor VEGFA to modulate its signaling through VEGFR2. The interactions between VEGFA and proteoglycan co-receptors require sulfated domains in the HS chains. To date, it is essentially unknown how the formation of sulfated protein-binding domains in HS can be regulated by microRNAs. In the present study, we show that microRNA-24 (miR-24) targets NDST1 to reduce HS sulfation and thereby the binding affinity of HS for VEGFA. Elevated levels of miR-24 also resulted in reduced levels of VEGFR2 and blunted VEGFA signaling. Similarly, suppression of NDST1 using siRNA led to a reduction in VEGFR2 expression. Consequently, not only VEGFA binding, but also VEGFR2 protein expression is dependent on NDST1 function. Furthermore, overexpression of miR-24, or siRNA-mediated reduction of NDST1, reduced endothelial cell chemotaxis in response to VEGFA. These findings establish NDST1 as a target of miR-24 and demonstrate how such NDST1 suppression in endothelial cells results in reduced responsiveness to VEGFA.
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| 9. |
- Kucharzewska, Paulina, et al.
(författare)
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Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development.
- 2013
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:18, s. 7312-7317
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia, or low oxygen tension, is a major regulator of tumor development and aggressiveness. However, how cancer cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Here, we show that secreted vesicles with exosome characteristics mediate hypoxia-dependent intercellular signaling of the highly malignant brain tumor glioblastoma multiforme (GBM). In vitro hypoxia experiments with glioma cells and studies with patient materials reveal the enrichment in exosomes of hypoxia-regulated mRNAs and proteins (e.g., matrix metalloproteinases, IL-8, PDGFs, caveolin 1, and lysyl oxidase), several of which were associated with poor glioma patient prognosis. We show that exosomes derived from GBM cells grown at hypoxic compared with normoxic conditions are potent inducers of angiogenesis ex vivo and in vitro through phenotypic modulation of endothelial cells. Interestingly, endothelial cells were programmed by GBM cell-derived hypoxic exosomes to secrete several potent growth factors and cytokines and to stimulate pericyte PI3K/AKT signaling activation and migration. Moreover, exosomes derived from hypoxic compared with normoxic conditions showed increased autocrine, promigratory activation of GBM cells. These findings were correlated with significantly enhanced induction by hypoxic compared with normoxic exosomes of tumor vascularization, pericyte vessel coverage, GBM cell proliferation, as well as decreased tumor hypoxia in a mouse xenograft model. We conclude that the proteome and mRNA profiles of exosome vesicles closely reflect the oxygenation status of donor glioma cells and patient tumors, and that the exosomal pathway constitutes a potentially targetable driver of hypoxia-dependent intercellular signaling during tumor development.
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| 10. |
- Lovén, Jakob, et al.
(författare)
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MYCN-regulated microRNAs repress estrogen receptor-alpha (ESR1) expression and neuronal differentiation in human neuroblastoma.
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:4, s. 1553-8
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Tidskriftsartikel (refereegranskat)abstract
- MYCN, a proto-oncogene normally expressed in the migrating neural crest, is in its amplified state a key factor in the genesis of human neuroblastoma (NB). However, the mechanisms underlying MYCN-mediated NB progression are poorly understood. Here, we present a MYCN-induced miRNA signature in human NB involving the activation and transrepression of several miRNA genes from paralogous clusters. Several family members derived from the miR-17 approximately 92 cluster, including miR-18a and miR-19a, were among the up-regulated miRNAs. Expression analysis of these miRNAs in NB tumors confirmed increased levels in MYCN-amplified samples. Specifically, we show that miR-18a and miR-19a target and repress the expression of estrogen receptor-alpha (ESR1), a ligand-inducible transcription factor implicated in neuronal differentiation. Immunohistochemical staining demonstrated ESR1 expression in human fetal sympathetic ganglia, suggesting a role for ESR1 during sympathetic nervous system development. Concordantly, lentiviral restoration of ESR1 in NB cells resulted in growth arrest and neuronal differentiation. Moreover, lentiviral-mediated inhibition of miR-18a in NB cells led to severe growth retardation, outgrowth of varicosity-containing neurites, and induction of neuronal sympathetic differentiation markers. Bioinformatic analyses of microarray data from NB tumors revealed that high ESR1 expression correlates with increased event-free survival in NB patients and favorable disease outcome. Thus, MYCN amplification may disrupt estrogen signaling sensitivity in primitive sympathetic cells through deregulation of ESR1, thereby preventing the normal induction of neuroblast differentiation. Collectively, our findings demonstrate the molecular consequences of abnormal miRNA transcription in a MYCN-driven tumor and offer unique insights into the pathology underlying MYCN-amplified NB.
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