An Object Oriented Architecture

We propose a new machine architecture for high performance execution of late binding object oriented languages The two principal mechanisms for attaining this goal are a fast context allocation/access scheme and an instruction translation lookaside buffer New ideas in this paper include the concept and implementation of abstract instructions, using floating point addresses to solve the small object problem, and a novel context allocation/access mechanis

Spontaneous jumping, bouncing and trampolining of hydrogel drops on a heated plate

Drops of liquid on a hot surface can exhibit fascinating behaviour such as the Leidenfrost effect in which drops hover on a vapour layer. Here Pham et al. show that when hydrogel drops are placed on a rapidly heated plate they bounce to increasing heights even if they were initially at rest

Submicron Systems Architecture: Semiannual Technical Report

No abstract available

Elevated expression of VEGFR-3 in lymphatic endothelial cells from lymphangiomas

<p>Abstract</p> <p>Background</p> <p>Lymphangiomas are neoplasias of childhood. Their etiology is unknown and a causal therapy does not exist. The recent discovery of highly specific markers for lymphatic endothelial cells (LECs) has permitted their isolation and characterization, but expression levels and stability of molecular markers on LECs from healthy and lymphangioma tissues have not been studied yet. We addressed this problem by profiling LECs from normal dermis and two children suffering from lymphangioma, and also compared them with blood endothelial cells (BECs) from umbilical vein, aorta and myometrial microvessels.</p> <p>Methods</p> <p>Lymphangioma tissue samples were obtained from two young patients suffering from lymphangioma in the axillary and upper arm region. Initially isolated with anti-CD31 (PECAM-1) antibodies, the cells were separated by FACS sorting and magnetic beads using anti-podoplanin and/or LYVE-1 antibodies. Characterization was performed by FACS analysis, immunofluorescence staining, ELISA and micro-array gene analysis.</p> <p>Results</p> <p>LECs from foreskin and lymphangioma had an almost identical pattern of lymphendothelial markers such as podoplanin, Prox1, reelin, cMaf and integrin-α1 and -α9. However, LYVE-1 was down-regulated and VEGFR-2 and R-3 were up-regulated in lymphangiomas. Prox1 was constantly expressed in LECs but not in any of the BECs.</p> <p>Conclusion</p> <p>LECs from different sources express slightly variable molecular markers, but can always be distinguished from BECs by their Prox1 expression. High levels of VEGFR-3 and -2 seem to contribute to the etiology of lymphangiomas.</p

Aggregatibacter actinomycetemcomitans Omp29 Is Associated with Bacterial Entry to Gingival Epithelial Cells by F-Actin Rearrangement

The onset and progressive pathogenesis of periodontal disease is thought to be initiated by the entry of Aggregatibacter actinomycetemcomitans (Aa) into periodontal tissue, especially gingival epithelium. Nonetheless, the mechanism underlying such bacterial entry remains to be clarified. Therefore, this study aimed to investigate the possible role of Aa outer membrane protein 29 kD (Omp29), a homologue of E. coli OmpA, in promoting bacterial entry into gingival epithelial cells. To accomplish this, Omp29 expression vector was incorporated in an OmpA-deficient mutant of E. coli. Omp29+/OmpA− E. coli demonstrated 22-fold higher entry into human gingival epithelial line cells (OBA9) than Omp29−/OmpA− E. coli. While the entry of Aa and Omp29+/OmpA− E. coli into OBA9 cells were inhibited by anti-Omp29 antibody, their adherence to OBA9 cells was not inhibited. Stimulation of OBA9 cells with purified Omp29 increased the phosphorylation of focal adhesion kinase (FAK), a pivotal cell-signaling molecule that can up-regulate actin rearrangement. Furthermore, Omp29 increased the formation of F-actin in OBA9 cells. The internalization of Omp29-coated beads and the entry of Aa into OBA9 were partially inhibited by treatment with PI3-kinase inhibitor (Wortmannin) and Rho GTPases inhibitor (EDIN), both known to convey FAK-signaling to actin-rearrangement. These results suggest that Omp29 is associated with the entry of Aa into gingival epithelial cells by up-regulating F-actin rearrangement via the FAK signaling pathway

Characterization and structural determination of a new anti-MET function-blocking antibody with binding epitope distinct from the ligand binding domain

The growth and motility factor Hepatocyte Growth Factor/Scatter Factor (HGF/SF) and its receptor, the product of the MET proto-oncogene, promote invasion and metastasis of tumor cells and have been considered potential targets for cancer therapy. We generated a new Met-blocking antibody which binds outside the ligand-binding site, and determined the crystal structure of the Fab in complex with its target, which identifies the binding site as the Met Ig1 domain. The antibody, 107_A07, inhibited HGF/SF-induced cell migration and proliferation in vitro and inhibited growth of tumor xenografts in vivo. In biochemical assays, 107_A07 competes with both HGF/SF and its truncated splice variant NK1 for MET binding, despite the location of the antibody epitope on a domain (Ig1) not reported to bind NK1 or HGF/SF. Overlay of the Fab-MET crystal structure with the InternalinB-MET crystal structure shows that the 107_A07 Fab comes into close proximity with the HGF/SF-binding SEMA domain when MET is in the “compact”, InternalinB-bound conformation, but not when MET is in the “open” conformation. These findings provide further support for the importance of the “compact” conformation of the MET extracellular domain, and the relevance of this conformation to HGF/SF binding and signaling

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire

BACKGROUND: Doppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo. METHODS: We perfused glass pipes of defined inner diameters (1.5 – 5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes. RESULTS: In vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r(2 )> 0.85). Above a critical Reynolds number of 500 – indicating turbulent flow – the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 ± 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments. CONCLUSION: Doppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making

A Framework for Exploring Functional Variability in Olfactory Receptor Genes

BACKGROUND: Olfactory receptors (ORs) are the largest gene family in mammalian genomes. Since nearly all OR genes are orphan receptors, inference of functional similarity or differences between odorant receptors typically relies on sequence comparisons. Based on the alignment of entire coding region sequence, OR genes are classified into families and subfamilies, a classification that is believed to be a proxy for OR gene functional variability. However, the assumption that overall protein sequence diversity is a good proxy for functional properties is untested. METHODOLOGY: Here, we propose an alternative sequence-based approach to infer the similarities and differences in OR binding capacity. Our approach is based on similarities and differences in the predicted binding pockets of OR genes, rather than on the entire OR coding region. CONCLUSIONS: Interestingly, our approach yields markedly different results compared to the analysis based on the entire OR coding-regions. While neither approach can be tested at this time, the discrepancy between the two calls into question the assumption that the current classification reliably reflects OR gene functional variability

Structural shape optimization using Cartesian grids and automatic h-adaptive mesh projection

[EN] We present a novel approach to 3D structural shape optimization that leans on an Immersed Boundary Method. A boundary tracking strategy based on evaluating the intersections between a fixed Cartesian grid and the evolving geometry sorts elements as internal, external and intersected. The integration procedure used by the NURBS-Enhanced Finite Element Method accurately accounts for the nonconformity between the fixed embedding discretization and the evolving structural shape, avoiding the creation of a boundary-fitted mesh for each design iteration, yielding in very efficient mesh generation process. A Cartesian hierarchical data structure improves the efficiency of the analyzes, allowing for trivial data sharing between similar entities or for an optimal reordering of thematrices for the solution of the system of equations, among other benefits. Shape optimization requires the sufficiently accurate structural analysis of a large number of different designs, presenting the computational cost for each design as a critical issue. The information required to create 3D Cartesian h- adapted mesh for new geometries is projected from previously analyzed geometries using shape sensitivity results. Then, the refinement criterion permits one to directly build h-adapted mesh on the new designs with a specified and controlled error level. Several examples are presented to show how the techniques here proposed considerably improve the computational efficiency of the optimization process.The authors wish to thank the Spanish Ministerio de Economia y Competitividad for the financial support received through the project DPI2013-46317-R and the FPI program (BES-2011-044080), and the Generalitat Valenciana through the project PROMETEO/2016/007.Marco, O.; Ródenas, J.; Albelda Vitoria, J.; Nadal, E.; Tur Valiente, M. (2017). Structural shape optimization using Cartesian grids and automatic h-adaptive mesh projection. Structural and Multidisciplinary Optimization. 1-21. https://doi.org/10.1007/s00158-017-1875-1S121MATLAB version 8.3.0.532 (R2014a) (2014) Documentation. The Mathworks, Inc., Natick, MassachusettsAbel JF, Shephard MS (1979) An algorithm for multipoint constraints in finite element analysis. Int J Numer Methods Eng 14(3):464–467Amestoy P, Davis T, Duff I (1996) An approximate minimum degree ordering algorithm. SIAM J Matrix Anal Appl 17(4):886–905Barth W, Stürzlinger W (1993) Efficient ray tracing for Bezier and B-spline surfaces. Comput Graph 17 (4):423–430Bennett J A, Botkin M E (1985) Structural shape optimization with geometric problem description and adaptive mesh refinement. AIAA J 23(3):459–464Braibant V, Fleury C (1984) Shape optimal design using b-splines. Comput Methods Appl Mech Eng 44 (3):247–267Bugeda G, Oliver J (1993) A general methodology for structural shape optimization problems using automatic adaptive remeshing. Int J Numer Methods Eng 36(18):3161–3185Bugeda G, Ródenas J J, Oñate E (2008) An integration of a low cost adaptive remeshing strategy in the solution of structural shape optimization problems using evolutionary methods. Comput Struct 86(13–14):1563–1578Chang K, Choi K K (1992) A geometry-based parameterization method for shape design of elastic solids. Mech Struct Mach 20(2):215–252Cho S, Ha S H (2009) Isogeometric shape design optimization: exact geometry and enhanced sensitivity. Struct Multidiscip Optim 38(1):53–70Belegundu D, Zhang YMS, Salagame R (1991) The natural approach for shape optimization with mesh distortion control. Tech. rep., Penn State UniversityDavis T A, Gilbert J R, Larimore S, Ng E (2004) An approximate column minimum degree ordering algorithm. ACM Trans Math Softw 30(3):353–376Doctor L J, Torborg J G (1981) Display techniques for octree-encoded objects. IEEE Comput Graph Appl 1(3):29–38Dunning P D, Kim H A, Mullineux G (2011) Investigation and improvement of sensitivity computation using the area-fraction weighted fixed grid FEM and structural optimization. Finite Elem Anal Des 47(8):933–941Düster A, Parvizian J, Yang Z, Rank E (2008) The finite cell method for three-dimensional problems of solid mechanics. Comput Methods Appl Mech Eng 197(45-48):3768–3782Escobar J M, Montenegro R, Rodríguez E, Cascón J M (2014) The meccano method for isogeometric solid modeling and applications. Eng Comput 30(3):331–343Farhat C, Lacour C, Rixen D (1998) Incorporation of linear multipoint constraints in substructure based iterative solvers. Part 1: a numerically scalable algorithm. Int J Numer Methods Eng 43(6):997–1016Fries T P, Omerović S (2016) Higher-order accurate integration of implicit geometries. Int J Numer Methods Eng 106(5):323–371Fuenmayor F J, Oliver J L (1996) Criteria to achieve nearly optimal meshes in the h-adaptive finite element mehod. Int J Numer Methods Eng 39(23):4039–4061Fuenmayor F J, Oliver J L, Ródenas J J (1997) Extension of the Zienkiewicz-Zhu error estimator to shape sensitivity analysis. Int J Numer Methods Eng 40(8):1413–1433García-Ruíz M J, Steven G P (1999) Fixed grid finite elements in elasticity problems. Eng Comput 16 (2):145–164Gill P, Murray W, Saunders M, Wright M (1984) Procedures for optimization problems with a mixture of bounds and general linear constraints. ACM Trans Math Software 10:282–298González-Estrada O A, Nadal E, Ródenas J J, Kerfriden P, Bordas S P A, Fuenmayor F J (2014) Mesh adaptivity driven by goal-oriented locally equilibrated superconvergent patch recovery. Comput Mech 53(5):957–976Ha S H, Choi K K, Cho S (2010) Numerical method for shape optimization using T-spline based isogeometric method. Struct Multidiscip Optim 42(3):417–428Haftka R T, Grandhi R V (1986) Structural shape optimization: A survey. Comput Methods Appl Mech Eng 57(1):91–106Haslinger J, Jedelsky D (1996) Genetic algorithms and fictitious domain based approaches in shape optimization. Struc Optim 12:257–264Hughes T J R, Cottrell J A, Bazilevs Y (2005) Isogeometric Analysis: CAD, Finite Elements, NURBS, Exact Geometry, and Mesh Refinement. Comput Methods Appl Mech Eng 194:4135–4195Jackins C L, Tanimoto S L (1980) Oct-tree and their use in representing three-dimensional objects. Comput Graphics Image Process 14(3):249–270Kajiya J T (1982) Ray Tracing Parametric Patches. SIGGRAPH Comput Graph 16(3):245–254van Keulen F, Haftka R T, Kim N (2005) Review of options for structural design sensitivity analysis. Part I: linear systems. Comput Methods Appl Mech Eng 194(30-33):3213–3243Kibsgaard S (1992) Sensitivity analysis-the basis for optimization. Int J Numer Methods Eng 34(3):901–932Kikuchi N, Chung K Y, Torigaki T, Taylor J E (1986) Adaptive finite element methods for shape optimization of linearly elastic structures. Comput Methods Appl Mech Eng 57(1):67–89Kim N H, Chang Y (2005) Eulerian shape design sensitivity analysis and optimization with a fixed grid. Comput Methods Appl Mech Eng 194(30–33):3291–3314Kudela L, Zander N, Kollmannsberger S, Rank E (2016) Smart octrees: Accurately integrating discontinuous functions in 3d. Comput Methods Appl Mech Eng 306(1):406–426Kunisch K, Peichl G (1996) Numerical gradients for shape optimization based on embedding domain techniques. Comput Optim 18:95–114Li K, Qian X (2011) Isogeometric analysis and shape optimization via boundary integral. Computer-Aided Design 43(11):1427–1437Lian H, Kerfriden P, Bordas S P A (2016) Implementation of regularized isogeometric boundary element methods for gradient-based shape optimization in two-dimensional linear elasticity. Int J Numer Methods Eng 106 (12):972–1017Liu L, Zhang Y, Hughes T J R, Scott M A, Sederberg T W (2014) Volumetric T-spline Construction using Boolean Operations. Eng Comput 30(4):425–439Marco O, Sevilla R, Zhang Y, Ródenas J J, Tur M (2015) Exact 3D boundary representation in finite element analysis based on Cartesian grids independent of the geometry. Int J Numer Methods Eng 103:445–468Marco O, Ródenas J J, Fuenmayor FJ, Tur M (2017a) An extension of shape sensitivity analysis to an immersed boundary method based on cartesian grids. Computational Mechanics SubmittedMarco O, Ródenas J J, Navarro-Jiménez JM, Tur M (2017b) Robust h-adaptive meshing strategy for arbitrary cad geometries in a cartesian grid framework. Computers & Structures SubmittedMeagher D (1980) Octree Encoding: A New Technique for the Representation, Manipulation and Display of Arbitrary 3-D Objects by Computer. Tech. Rep. IPL-TR-80-11 I, Rensselaer Polytechnic InstituteMoita J S, Infante J, Mota C M, Mota C A (2000) Sensitivity analysis and optimal design of geometrically non-linear laminated plates and shells. Comput Struct 76(1–3):407–420Nadal E (2014) Cartesian Grid FEM (cgFEM): High Performance h-adaptive FE Analysis with Efficient Error Control. Application to Structural Shape Optimization. PhD Thesis. Universitat Politècnica de ValènciaNadal E, Ródenas J J, Albelda J, Tur M, Tarancón J E, Fuenmayor F J (2013) Efficient finite element methodology based on cartesian grids: application to structural shape optimization. Abstr Appl Anal 2013:1–19Najafi A R, Safdari M, Tortorelli D A, Geubelle P H (2015) A gradient-based shape optimization scheme using an interface-enriched generalized FEM. Comput Methods Appl Mech Eng 296:1–17Nguyen V P, Anitescu C, Bordas S P A, Rabczuk T (2015) Isogeometric analysis: An overview and computer implementation aspects. Math Comput Simul 117:89–116Nishita T, Sederberg TW, Kakimoto M (1990) Ray Tracing Trimmed Rational Surface Patches. SIGGRAPH Comput Graph 24(4):337–345Nocedal J, Wright SJ (2006) Numerical optimization, 2nd edn. Springer-Verlag, New YorkPandey P C, Bakshi P (1999) Analytical response sensitivity computation using hybrid finite elements. Comput Struct 71(5):525–534Parvizian J, Düster A, Rank E (2007) Finite Cell Method: h- and p- Extension for Embedded Domain Methods in Solid Mechanics. Comput Mech 41(1):121–133Peskin C S (1977) Numerical Analysis of Blood Flow in the Heart. J Comput Phys 25:220–252Poldneff M J, Rai I S, Arora J S (1993) Implementation of design sensitivity analysis for nonlinear structures. AIAA J 31(11):2137–2142Powell M (1983) Variable metric methods for constrained optimization. In: Bachem A, Grotschel M, Korte B (eds) Mathematical Programming: The State of the Art, Springer, Berlin, Heidelberg, pp 288–311Qian X (2010) Full analytical sensitivities in NURBS based isogeometric shape optimization. Comput Methods Appl Mech Eng 199(29–32):2059–2071Riehl S, Steinmann P (2014) An integrated approach to shape optimization and mesh adaptivity based on material residual forces. Comput Methods Appl Mech Eng 278:640–663Riehl S, Steinmann P (2016) On structural shape optimization using an embedding domain discretization technique. Int J Numer Methods Eng 109(9):1315–1343Ródenas J J, Tarancón J E, Albelda J, Roda A, Fuenmayor F J (2005) Hierarchical Properties in Elements Obtained by Subdivision: a Hierarquical h-adaptivity Program. In: Díez P, Wiberg N E (eds) Adaptive Modeling and Simulation, p 2005Ródenas J J, Corral C, Albelda J, Mas J, Adam C (2007a) Nested domain decomposition direct and iterative solvers based on a hierarchical h-adaptive finite element code. In: Runesson K, Díez P (eds) Adaptive Modeling and Simulation 2007, Internacional Center for Numerical Methods in Engineering (CIMNE), pp 206–209Ródenas J J, Tur M, Fuenmayor F J, Vercher A (2007b) Improvement of the superconvergent patch recovery technique by the use of constraint equations: the SPR-C technique. Int J Numer Methods Eng 70(6):705–727Ródenas J J, Bugeda G, Albelda J, Oñate E (2011) On the need for the use of error-controlled finite element analyses in structural shape optimization processes. Int J Numer Methods Eng 87(11):1105–1126Schillinger D, Ruess M (2015) The finite cell method: A review in the context of higher-order structural analysis of cad and image-based geometric models. Arch Comput Meth Eng 22(3):391– 455Sevilla R, Fernández-Méndez S, Huerta A (2011a) 3D-NURBS-enhanced Finite Element Method (NEFEM). Int J Numer Methods Eng 88(2):103–125Sevilla R, Fernández-Méndez S, Huerta A (2011b) Comparison of High-order Curved Finite Elements. Int J Numer Methods Eng 87(8):719–734Sevilla R, Fernández-Méndez S, Huerta A (2011c) NURBS-enhanced Finite Element Method (NEFEM): A Seamless Bridge Between CAD and FEM. Arch Comput Meth Eng 18(4):441–484Sweeney M, Bartels R (1986) Ray tracing free-form b-spline surfaces. IEEE Comput Graph Appl 6(2):41–49Toth D L (1985) On Ray Tracing Parametric Surfaces. SIGGRAPH Comput Graph 19(3):171–179Tur M, Albelda J, Nadal E, Ródenas J J (2014) Imposing dirichlet boundary conditions in hierarchical cartesian meshes by means of stabilized lagrange multipliers. Int J Numer Methods Eng 98(6):399–417Tur M, Albelda J, Marco O, Ródenas J J (2015) Stabilized Method to Impose Dirichlet Boundary Conditions using a Smooth Stress Field. Comput Methods Appl Mech Eng 296:352–375Yao T, Choi KK (1989) 3-d shape optimal design and automatic finite element regridding. Int J Numer Methods Eng 28(2):369–384Zhang L, Gerstenberger A, Wang X, Liu W K (2004) Immersed Finite Element Method. Comput Methods Appl Mech Eng 293(21):2051–2067Zhang Y, Wang W, Hughes T J R (2013) Conformal Solid T-spline Construction from Boundary T-spline Representations. Comput Mech 6(51):1051–1059Zienkiewicz O C, Zhu J Z (1987) A Simple Error Estimator and Adaptive Procedure for Practical Engineering Analysis. Int J Numer Methods Eng 24(2):337–35