La inactividad de la administración en el ejercicio de la potestad de restablecimiento del orden urbanístico infringido por las edificaciones ilegales

La hipotesis de la tesis se basa en la indolencia de la administracion publica y su falta de aplicacion en el cumplimiento del deber de proteccion de la legalidad urbanistica frente a una edificacion ilegal. la proposicion que se mantiene es que el establecimiento de configuraciones singularizadas y de diferentes plazos para ejercitar la accion de restauracion de la legalidad urbanistica, por los poderes legislativos de las ccaa, contraviene el principio constitucional de igualdad en el ejercicio del derecho de propiedad privada del suelo y que la falta de actuacion del poder de proteccion de la legalidad ya no puede constituir, desde la entrada en vigor de la ley del suelo de 2007, un hecho juridico en virtud del cual el propietario del suelo pudiera patrimonializar el valor urbanistico de una edificacion ilegal. porque solo los criterios legales de valoracion determinan el alcance patrimonial de las facultades que pueden llegar a formar parte del contenido del derecho de propiedad del suelo. a traves del trabajo se ha podido deducir que, pese al reconocimiento legal del concepto estatutario del derecho de propiedad del suelo, se ha seguido manteniendo una concepcion civilista del derecho, que, unida a la falta de control de la inactividad administrativa, ha derivado, cuando la administracion ya no podia ejercitar la accion de restauracion de esa legalidad por el transcurso de los plazos, en la equiparacion de la edificacion ilegal a las edificaciones legales, o en su asimilacion a las edificaciones en situacion de fuera de ordenacion. los diferentes plazos de caducidad o de prescripcion de la citada accion han creado importantes disfunciones del principio establecido en el articulo 149.1.1 ce, por lo que los objetivos de la investigacion ha sido acreditar la necesidad de una regulacion igualitaria para todo el estado de la actuacion de la administracion frente a la ilegalidad edificatoria y que el ejercicio de la potestad de restablecimiento de la legalidad no se sujete a plazo

Modelización tridimensional mediante técnicas SFM de vuelos fotogramétricos antiguos. Evaluación de posibilidades aplicadas al vuelo de 1957

[ES] En la realización del presente proyecto, se pretende estudiar la obtención de Modelos Digitales de Superficies (MDS) y Modelos Digitales de Elevaciones (MDE) utilizando la técnica ‘Structure for Motion’ (SfM), aplicada mediante el software Agisoft-Photoscan sobre fotogramas antiguos con recubrimiento longitudinal entre ellos. El objetivo es recuperar la configuración 3D de áreas actualmente modificadas por la acción humana. En el trabajo se aprenderá a usar la técnica SfM (con el programa indicado), generando así una nube de puntos a partir de los fotogramas iniciales. Dicho resultado se transformará generando un archivo en formato *.las, del que, posteriormente, se eliminarán los elementos que se encuentren sobre la superficie terrestre (mediante el empleo del software FUSION). Finalmente, a partir del resultado obtenido, se generarán tanto un Modelo Digital de Elevaciones, como un Modelo Digital de Superficies que se podrán comparar con el modelo actual, así como evaluar la calidad del resultado obtenido mediante la utilización de análisis estadísticos. De esta manera podrán observarse los cambios tanto en el MDS como en el MDE a través del paso del tiempo. La aplicación de la metodología explicada anteriormente se realizará sobre una recopilación de imágenes de un vuelo aéreo efectuado en el momento de la riada de 1957, correspondientes a una zona situada en el barranco de la castellana, dentro de los términos municipales de Llíria y Domeño. Las imágenes en cuestión corresponden a un vuelo no oficial y han sido tratadas a posteriori, llegando a nosotros como fotogramas escaneados y modificados geométricamente a través del recorte de los márgenes originales.[EN] Through the realization of this Thesis, the intention is to study the production of Digital Surface Models (DSM) and Digital Elevation Models (DEM) using the technique 'Structure from Motion' (SfM), applied by Agisoft-Photoscan software on old aerial photographs with longitudinal overlapping. The goal is to recover the 3D configuration of areas currently modified by human action. In this thesis it will be explained how to use the SfM technique (with the indicated software), generating a point cloud from the initial images. This result will be converted generating a file in *.las format, from which the elements that remain over the earth's surface will be deleted (by using FUSION software). Finally, from the result, either a Digital Elevation Model, as a Digital Surface Model will be generated, allowing the comparison with the current model. Furthermore, the quality of the result obtained will be evaluated by using statistical analysis. By this way, changes can be evaluated in both the MDS and MDE through the time. The application of the methodology explained above is carried out on a collection of images of an air flight made at the time of the flood of 1957, corresponding to an area located in the gorge named ‘Barranco de la Castellana’, within the municipalities of Llíria and Domeño. The images of the study correspond to an unofficial flight and have been treated after it, coming to us as scanned frames and geometrically modified by cutting the original margins.[CA] En la realització d’aquest projecte, es pretén estudiar l’obtenció de Models Digitals de Superfícies (MDS) i Models Digitals d’Elevacions (MDE) utilitzant la tècnica “Structure for Motion” (SfM), aplicada mitjançant el software Agisoft-Photoscan sobre fotogrames antics amb recobriment longitudinal entre ells. L’objectiu és recuperar la configuració 3D d’àrees actualment modificades per l’acció humana. En el treball s’aprendrà a utilitzar la tècnica SfM (amb el programa indicat), generant així un núvol de punts a partir dels fotogrames inicials. Aquest resultat es transformarà tot generant un arxiu en format *.las del qual, posteriorment s’eliminaran els elements que s’hi troben sobre la superfície terrestre (mitjançant l’ús del software FUSION). Finalment, a partir del resultat obtingut, es generaran tant un Model Digital d’Elevacions com un Model Digital de Superfícies, les quals es podran comparar amb el model actual. D’altra banda, també es podrà avaluar la qualitat del resultat obtingut mitjançant la utilització d’anàlisi estadístics. D’aquesta manera es podran observar els canvis, tant en el MDS com en el MDE a través del pas del temps. L’aplicació de la metodologia explicada anteriorment es realitzarà sobre una recopilació d’imatges d’un vol aeri efectuat en el moment de la riuada de 1957, corresponents a una zona situada en el barranc de La Castellana, dins dels termes municipals de Llíria i Domeño. Les imatges en qüestió corresponen a un vol no oficial i han estat tractades a posteriori. Aquestes han arribat a nosaltres com a fotogrames escanejats i modificats geomètricament a través del retall dels marges originals.Parrizas Siles, M. (2016). Modelización tridimensional mediante técnicas SFM de vuelos fotogramétricos antiguos. Evaluación de posibilidades aplicadas al vuelo de 1957. Universitat Politècnica de València. http://hdl.handle.net/10251/68378TFG

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio

Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling

Adherent epithelial cells require interactions with the extracellular matrix for their survival, though the mechanism is ill-defined. In long term cultures of primary mammary epithelial cells, a laminin-rich basement membrane (BM) but not collagen I suppresses apoptosis, indicating that adhesion survival signals are specific in their response (Pullan et al. 1996. J. Cell Sci. 109:631–642). We now demonstrate that the signal from BM is mediated by integrins and requires both the α6 and β1 subunits. In addition, a hormonal signal from insulin or insulin-like growth factors, but not hydrocortisone or prolactin, is necessary to suppress mammary cell apoptosis, indicating that BM and soluble factors cooperate in survival signaling. Insulin induced autophosphorylation of its receptor whether mammary cells were cultured on collagen I or BM substrata. However, both the tyrosine phosphorylation of insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase were enhanced in cells cultured on BM, as was the phosphorylation of the phosphatidylinositol 3-kinase effector, protein kinase B. These results suggest a novel extracellular matrix–dependent restriction point in insulin signaling in mammary epithelial cells. The proximal signal transduction event of insulin receptor phosphorylation is not dependent on extracellular matrix, but the activation of downstream effectors requires adhesion to BM. Since phosphatidylinositol 3-kinase was required for mammary epithelial cell survival, we propose that a possible mechanism for BM-mediated suppression of apoptosis is through its facilitative effects on insulin signaling

A Neutrophil Timer Coordinates Immune Defense and Vascular Protection

Neutrophils eliminate pathogens efficiently but can inflict severe damage to the host if they over-activate within blood vessels. It is unclear how immunity solves the dilemma of mounting an efficient anti-microbial defense while preserving vascular health. Here, we identify a neutrophil-intrinsic program that enabled both. The gene Bmal1 regulated expression of the chemokine CXCL2 to induce chemokine receptor CXCR2-dependent diurnal changes in the transcriptional and migratory properties of circulating neutrophils. These diurnal alterations, referred to as neutrophil aging, were antagonized by CXCR4 (C-X-C chemokine receptor type 4) and regulated the outer topology of neutrophils to favor homeostatic egress from blood vessels at night, resulting in boosted anti-microbial activity in tissues. Mice engineered for constitutive neutrophil aging became resistant to infection, but the persistence of intravascular aged neutrophils predisposed them to thrombo-inflammation and death. Thus, diurnal compartmentalization of neutrophils, driven by an internal timer, coordinates immune defense and vascular protection. Neutrophils display circadian oscillations in numbers and phenotype in the circulation. Adrover and colleagues now identify the molecular regulators of neutrophil aging and show that genetic disruption of this process has major consequences in immune cell trafficking, anti-microbial defense, and vascular health.This study was supported by Intramural grants from A∗STAR to L.G.N., BES-2013-065550 to J.M.A., BES-2010-032828 to M.C.-A, and JCI-2012-14147 to L.A.W (all from Ministerio de Economía, Industria y Competitividad; MEIC). Additional MEIC grants were SAF2014-61993-EXP to C.L.-R.; SAF2015-68632-R to M.A.M. and SAF-2013-42920R and SAF2016-79040Rto D.S. D.S. also received 635122-PROCROP H2020 from the European Commission and ERC CoG 725091 from the European Research Council (ERC). ERC AdG 692511 PROVASC from the ERC and SFB1123-A1 from the Deutsche Forschungsgemeinschaft were given to C.W.; MHA VD1.2/81Z1600212 from the German Center for Cardiovascular Research (DZHK) was given to C.W. and O.S.; SFB1123-A6 was given to O.S.; SFB914-B08 was given to O.S. and C.W.; and INST 211/604-2, ZA 428/12-1, and ZA 428/13-1 were given to A.Z. This study was also supported by PI12/00494 from Fondo de Investigaciones Sanitarias (FIS) to C.M.; PI13/01979, Cardiovascular Network grant RD 12/0042/0054, and CIBERCV to B.I.; SAF2015-65607-R, SAF2013-49662-EXP, and PCIN-2014-103 from MEIC; and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) to A.H. The CNIC is supported by the MEIC and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505)

A Neutrophil Timer Coordinates Immune Defense and Vascular Protection

Neutrophils eliminate pathogens efficiently but can inflict severe damage to the host if they over-activate within blood vessels. It is unclear how immunity solves the dilemma of mounting an efficient anti-microbial defense while preserving vascular health. Here, we identify a neutrophil-intrinsic program that enabled both. The gene Bmal1 regulated expression of the chemokine CXCL2 to induce chemokine receptor CXCR2-dependent diurnal changes in the transcriptional and migratory properties of circulating neutrophils. These diurnal alterations, referred to as neutrophil aging, were antagonized by CXCR4 (C-X-C chemokine receptor type 4) and regulated the outer topology of neutrophils to favor homeostatic egress from blood vessels at night, resulting in boosted anti-microbial activity in tissues. Mice engineered for constitutive neutrophil aging became resistant to infection, but the persistence of intravascular aged neutrophils predisposed them to thrombo-inflammation and death. Thus, diurnal compartmentalization of neutrophils, driven by an internal timer, coordinates immune defense and vascular protection.We thank all members of the Hidalgo Lab for discussion and insightful comments; J.M. Ligos, R. Nieto, and M. Viton for help with sorting and cytometric analyses; I. Ortega and E. Santos for animal husbandry; D. Rico, M.J. Gomez, C. Torroja, and F. Sanchez-Cabo for insightful comments and help with transcriptomic analyses; V. Labrador, E. Arza, A.M. Santos, and the Microscopy Unit of the CNIC for help with microscopy; S. Aznar-Benitah, U. Albrecht, Q.-J. Meng, B. Staels, and H. Duez for the generous gift of mice; J.A. Enriquez and J. Avila for scientific insights; and J.M. Garcia and A. Diez de la Cortina for art. This study was supported by Intramural grants from A* STAR to L.G.N., BES-2013-065550 to J.M.A., BES-2010-032828 to M.C.-A, and JCI-2012-14147 to L.A.W (all from Ministerio de Economia, Industria y Competitividad; MEIC). Additional MEIC grants were SAF2014-61993-EXP to C.L.-R.; SAF2015-68632-R to M.A.M. and SAF-2013-42920R and SAF2016-79040Rto D.S. D.S. also received 635122-PROCROP H2020 from the European Commission and ERC CoG 725091 from the European Research Council (ERC). ERC AdG 692511 PROVASC from the ERC and SFB1123-A1 from the Deutsche Forschungsgemeinschaft were given to C.W.; MHA VD1.2/81Z1600212 from the German Center for Cardiovascular Research (DZHK) was given to C.W. and O.S.; SFB1123-A6 was given to O.S.; SFB914-B08 was given to O.S. and C.W.; and INST 211/604-2, ZA 428/12-1, and ZA 428/13-1 were given to A.Z. This study was also supported by PI12/00494 from Fondo de Investigaciones Sanitarias (FIS) to C.M.; PI13/01979, Cardiovascular Network grant RD 12/0042/0054, and CIBERCV to B.I.; SAF2015-65607-R, SAF2013-49662-EXP, and PCIN-2014-103 from MEIC; and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) to A.H. The CNIC is supported by the MEIC and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505).S

Epistasis of Transcriptomes Reveals Synergism between Transcriptional Activators Hnf1α and Hnf4α

The transcription of individual genes is determined by combinatorial interactions between DNA–binding transcription factors. The current challenge is to understand how such combinatorial interactions regulate broad genetic programs that underlie cellular functions and disease. The transcription factors Hnf1α and Hnf4α control pancreatic islet β-cell function and growth, and mutations in their genes cause closely related forms of diabetes. We have now exploited genetic epistasis to examine how Hnf1α and Hnf4α functionally interact in pancreatic islets. Expression profiling in islets from either Hnf1a+/− or pancreas-specific Hnf4a mutant mice showed that the two transcription factors regulate a strikingly similar set of genes. We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1α on Hnf4a gene transcription. Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1α and Hnf4α regulate common targets synergistically. Hnf1α binding in Hnf4a-deficient islets was decreased in selected targets, but remained unaltered in others, thus suggesting that the mechanisms for synergistic regulation are gene-specific. These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1α and Hnf4α control a common islet-cell regulatory program that is defective in human monogenic diabetes

A Serum Factor Induces Insulin-Independent Translocation of GLUT4 to the Cell Surface which Is Maintained in Insulin Resistance

In response to insulin, glucose transporter GLUT4 translocates from intracellular compartments towards the plasma membrane where it enhances cellular glucose uptake. Here, we show that sera from various species contain a factor that dose-dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes, human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate that the serum-induced increase in cell surface GLUT4 levels is not due to inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that of insulin, while it also sensitizes the cells to insulin. In accordance with these findings, serum does not appear to activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 translocation. We conclude that in addition to insulin, at least one other biological proteinaceous factor exists that contributes to GLUT4 regulation and still functions in insulin resistance. The challenge now is to identify this factor