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Author |
David Roche; Debora Gil; Jesus Giraldo |
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Title |
Mechanistic analysis of the function of agonists and allosteric modulators: Reconciling two-state and operational models |
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Journal Article |
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2013 |
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British Journal of Pharmacology |
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BJP |
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169 |
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6 |
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1189-202 |
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Two-state and operational models of both agonism and allosterism are compared to identify and characterize common pharmacological parameters. To account for the receptor-dependent basal response, constitutive receptor activity is considered in the operational models. By arranging two-state models as the fraction of active receptors and operational models as the fractional response relative to the maximum effect of the system, a one-by-one correspondence between parameters is found. The comparative analysis allows a better understanding of complex allosteric interactions. In particular, the inclusion of constitutive receptor activity in the operational model of allosterism allows the characterization of modulators able to lower the basal response of the system; that is, allosteric modulators with negative intrinsic efficacy. Theoretical simulations and overall goodness of fit of the models to simulated data suggest that it is feasible to apply the models to experimental data and constitute one step forward in receptor theory formalism. |
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IAM; 600.044; 605.203 |
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IAM @ iam @ RGG2013b |
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2195 |
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Author |
David Roche; Debora Gil; Jesus Giraldo |
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Title |
Mathematical modeling of G protein-coupled receptor function: What can we learn from empirical and mechanistic models? |
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Book Chapter |
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Year |
2014 |
Publication |
G Protein-Coupled Receptors – Modeling and Simulation Advances in Experimental Medicine and Biology |
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796 |
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3 |
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159-181 |
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β-arrestin; biased agonism; curve fitting; empirical modeling; evolutionary algorithm; functional selectivity; G protein; GPCR; Hill coefficient; intrinsic efficacy; inverse agonism; mathematical modeling; mechanistic modeling; operational model; parameter optimization; receptor dimer; receptor oligomerization; receptor constitutive activity; signal transduction; two-state model |
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Empirical and mechanistic models differ in their approaches to the analysis of pharmacological effect. Whereas the parameters of the former are not physical constants those of the latter embody the nature, often complex, of biology. Empirical models are exclusively used for curve fitting, merely to characterize the shape of the E/[A] curves. Mechanistic models, on the contrary, enable the examination of mechanistic hypotheses by parameter simulation. Regretfully, the many parameters that mechanistic models may include can represent a great difficulty for curve fitting, representing, thus, a challenge for computational method development. In the present study some empirical and mechanistic models are shown and the connections, which may appear in a number of cases between them, are analyzed from the curves they yield. It may be concluded that systematic and careful curve shape analysis can be extremely useful for the understanding of receptor function, ligand classification and drug discovery, thus providing a common language for the communication between pharmacologists and medicinal chemists. |
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Springer Netherlands |
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0065-2598 |
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978-94-007-7422-3 |
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IAM; 600.075 |
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IAM @ iam @ RGG2014 |
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2197 |
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Author |
Debora Gil; Jaume Garcia; Aura Hernandez-Sabate; Enric Marti |
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Title |
Manifold parametrization of the left ventricle for a statistical modelling of its complete anatomy |
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Conference Article |
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2010 |
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8th Medical Imaging |
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7623 |
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762304 |
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304 |
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Distortion of Left Ventricle (LV) external anatomy is related to some dysfunctions, such as hypertrophy. The architecture of myocardial fibers determines LV electromechanical activation patterns as well as mechanics. Thus, their joined modelling would allow the design of specific interventions (such as peacemaker implantation and LV remodelling) and therapies (such as resynchronization). On one hand, accurate modelling of external anatomy requires either a dense sampling or a continuous infinite dimensional approach, which requires non-Euclidean statistics. On the other hand, computation of fiber models requires statistics on Riemannian spaces. Most approaches compute separate statistical models for external anatomy and fibers architecture. In this work we propose a general mathematical framework based on differential geometry concepts for computing a statistical model including, both, external and fiber anatomy. Our framework provides a continuous approach to external anatomy supporting standard statistics. We also provide a straightforward formula for the computation of the Riemannian fiber statistics. We have applied our methodology to the computation of complete anatomical atlas of canine hearts from diffusion tensor studies. The orientation of fibers over the average external geometry agrees with the segmental description of orientations reported in the literature. |
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SPIE |
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SPIE |
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IAM |
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no |
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IAM @ iam @ GGH2010a |
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1522 |
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Author |
Esmitt Ramirez; Carles Sanchez; Debora Gil |
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Title |
Localizing Pulmonary Lesions Using Fuzzy Deep Learning |
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Conference Article |
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Year |
2019 |
Publication |
21st International Symposium on Symbolic and Numeric Algorithms for Scientific Computing |
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290-294 |
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The usage of medical images is part of the clinical daily in several healthcare centers around the world. Particularly, Computer Tomography (CT) images are an important key in the early detection of suspicious lung lesions. The CT image exploration allows the detection of lung lesions before any invasive procedure (e.g. bronchoscopy, biopsy). The effective localization of lesions is performed using different image processing and computer vision techniques. Lately, the usage of deep learning models into medical imaging from detection to prediction shown that is a powerful tool for Computer-aided software. In this paper, we present an approach to localize pulmonary lung lesion using fuzzy deep learning. Our approach uses a simple convolutional neural network based using the LIDC-IDRI dataset. Each image is divided into patches associated a probability vector (fuzzy) according their belonging to anatomical structures on a CT. We showcase our approach as part of a full CAD system to exploration, planning, guiding and detection of pulmonary lesions. |
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Timisoara; Rumania; September 2019 |
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SYNASC |
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IAM; 600.145; 600.140; 601.337; 601.323 |
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no |
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Admin @ si @ RSG2019 |
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3531 |
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Author |
Patricia Marquez; Debora Gil; R.Mester; Aura Hernandez-Sabate |
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Title |
Local Analysis of Confidence Measures for Optical Flow Quality Evaluation |
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Conference Article |
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Year |
2014 |
Publication |
9th International Conference on Computer Vision Theory and Applications |
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3 |
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450-457 |
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Optical Flow; Confidence Measure; Performance Evaluation. |
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Optical Flow (OF) techniques facing the complexity of real sequences have been developed in the last years. Even using the most appropriate technique for our specific problem, at some points the output flow might fail to achieve the minimum error required for the system. Confidence measures computed from either input data or OF output should discard those points where OF is not accurate enough for its further use. It follows that evaluating the capabilities of a confidence measure for bounding OF error is as important as the definition
itself. In this paper we analyze different confidence measures and point out their advantages and limitations for their use in real world settings. We also explore the agreement with current tools for their evaluation of confidence measures performance. |
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Lisboa; January 2014 |
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VISAPP |
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IAM; ADAS; 600.044; 600.060; 600.057; 601.145; 600.076; 600.075 |
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no |
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Admin @ si @ MGM2014 |
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2432 |
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Author |
Antoni Gurgui; Debora Gil; Enric Marti; Vicente Grau |
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Title |
Left-Ventricle Basal Region Constrained Parametric Mapping to Unitary Domain |
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Conference Article |
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2016 |
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7th International Workshop on Statistical Atlases & Computational Modelling of the Heart |
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10124 |
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163-171 |
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Laplacian; Constrained maps; Parameterization; Basal ring |
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Due to its complex geometry, the basal ring is often omitted when putting different heart geometries into correspondence. In this paper, we present the first results on a new mapping of the left ventricle basal rings onto a normalized coordinate system using a fold-over free approach to the solution to the Laplacian. To guarantee correspondences between different basal rings, we imposed some internal constrained positions at anatomical landmarks in the normalized coordinate system. To prevent internal fold-overs, constraints are handled by cutting the volume into regions defined by anatomical features and mapping each piece of the volume separately. Initial results presented in this paper indicate that our method is able to handle internal constrains without introducing fold-overs and thus guarantees one-to-one mappings between different basal ring geometries. |
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Athens; October 2016 |
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LNCS |
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STACOM |
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IAM; |
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Admin @ si @ GGM2016 |
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2884 |
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Francesc Carreras; Jaume Garcia; Debora Gil; Sandra Pujadas; Chi ho Lion; R.Suarez-Arias; R.Leta; Xavier Alomar; Manuel Ballester; Guillem Pons-Llados |
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Left ventricular torsion and longitudinal shortening: two fundamental components of myocardial mechanics assessed by tagged cine-MRI in normal subjects |
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Journal Article |
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2012 |
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International Journal of Cardiovascular Imaging |
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IJCI |
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28 |
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2 |
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273-284 |
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Magnetic resonance imaging (MRI); Tagging MRI; Cardiac mechanics; Ventricular torsion |
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Cardiac magnetic resonance imaging (Cardiac MRI) has become a gold standard diagnostic technique for the assessment of cardiac mechanics, allowing the non-invasive calculation of left ventric- ular long axis longitudinal shortening (LVLS) and absolute myocardial torsion (AMT) between basal and apical left ventricular slices, a movement directly related to the helicoidal anatomic disposition of the myocardial fibers. The aim of this study is to determine AMT and LVLS behaviour and normal values from a group of healthy subjects. A group of 21 healthy volunteers (15 males) (age: 23–55 y.o., mean:30.7 ± 7.5) were prospectively included in an obser- vational study by Cardiac MRI. Left ventricular rotation (degrees) was calculated by custom-made software (Harmonic Phase Flow) in consecutive LV short axis planes tagged cine-MRI sequences. AMT was determined from the difference between basal and apical planes LV rotations. LVLS (%) was determined from the LV longitudinal and horizontal axis cine-MRI images. All the 21 cases studied were interpretable, although in three cases the value of the LV apical rotation could not be determined. The mean rotation of the basal and apical planes at end-systole were -3.71° ± 0.84° and 6.73° ± 1.69° (n:18) respectively, resulting in a LV mean AMT of 10.48° ± 1.63° (n:18). End-systolic mean LVLS was 19.07 ± 2.71%. Cardiac MRI allows for the calculation of AMT and LVLS, fundamental functional components of the ventricular twist mechanics conditioned, in turn, by the anatomical helical layout of the myocardial fibers. These values provide complementary information about systolic ventricular function in relation to the traditional parameters used in daily practice. |
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Springer Netherlands |
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1569-5794 |
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IAM; |
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IAM @ iam @ CGG2012 |
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1496 |
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Author |
Antoni Gurgui; Debora Gil; Enric Marti |
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Title |
Laplacian Unitary Domain for Texture Morphing |
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Conference Article |
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2015 |
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Proceedings of the 10th International Conference on Computer Vision Theory and Applications VISIGRAPP2015 |
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1 |
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693-699 |
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Facial; metamorphosis;LaplacianMorphing |
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Deformation of expressive textures is the gateway to realistic computer synthesis of expressions. By their good mathematical properties and flexible formulation on irregular meshes, most texture mappings rely on solutions to the Laplacian in the cartesian space. In the context of facial expression morphing, this approximation can be seen from the opposite point of view by neglecting the metric. In this paper, we use the properties of the Laplacian in manifolds to present a novel approach to warping expressive facial images in order to generate a morphing between them. |
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Munich; Germany; February 2015 |
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SciTePress |
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978-989-758-089-5 |
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VISAPP |
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IAM; 600.075 |
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Admin @ si @ GGM2015 |
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2614 |
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Author |
Debora Gil; Petia Radeva; Josefina Mauri |
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Title |
Ivus Segmentation Via a Regularized Curvature Flow |
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Conference Article |
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2002 |
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X Congreso Anual de la Sociedad Española de Ingeniería Biomédica CASEIB 2002 |
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133-136 |
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Cardiac diseases are diagnosed and treated through a study of the morphology and dynamics of cardiac arteries. In- travascular Ultrasound (IVUS) imaging is of high interest to physicians since it provides both information. At the current state-of-the-art in image segmentation, a robust detection of the arterial lumen in IVUS demands manual intervention or ECG-gating. Manual intervention is a tedious and time consuming task that requires experienced observers, meanwhile ECG-gating is an acquisition technique not available in all clinical centers. We introduce a parametric algorithm that detects the arterial luminal border in in vivo sequences. The method consist in smoothing the sequences’ level surfaces under a regularized mean curvature flow that admits non-trivial steady states. The flow is based on a measure of the surface local smoothness that takes into account regularity of the surface curvature. |
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Saragossa, Espanya |
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IAM;MILAB |
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IAM @ iam @ GRM2002 |
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1536 |
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Mireia Sole; Joan Blanco; Debora Gil; G. Fonseka; Richard Frodsham; Oliver Valero; Francesca Vidal; Zaida Sarrate |
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Is there a pattern of Chromosome territoriality along mice spermatogenesis? |
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Conference Article |
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2017 |
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3rd Spanish MeioNet Meeting Abstract Book |
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55-56 |
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Miraflores de la Sierra; Madrid; June 2017 |
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MEIONET |
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IAM; 600.096; 600.145 |
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Admin @ si @ |
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2958 |
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