Is Geo-Indistinguishability What You Are Looking for?

Since its proposal in 2013, geo-indistinguishability has been consolidated as a formal notion of location privacy, generating a rich body of literature building on this idea. A problem with most of these follow-up works is that they blindly rely on geo-indistinguishability to provide location privacy, ignoring the numerical interpretation of this privacy guarantee. In this paper, we provide an alternative formulation of geo-indistinguishability as an adversary error, and use it to show that the privacy vs.~utility trade-off that can be obtained is not as appealing as implied by the literature. We also show that although geo-indistinguishability guarantees a lower bound on the adversary's error, this comes at the cost of achieving poorer performance than other noise generation mechanisms in terms of average error, and enabling the possibility of exposing obfuscated locations that are useless from the quality of service point of view

Rethinking Location Privacy for Unknown Mobility Behaviors

Location Privacy-Preserving Mechanisms (LPPMs) in the literature largely consider that users' data available for training wholly characterizes their mobility patterns. Thus, they hardwire this information in their designs and evaluate their privacy properties with these same data. In this paper, we aim to understand the impact of this decision on the level of privacy these LPPMs may offer in real life when the users' mobility data may be different from the data used in the design phase. Our results show that, in many cases, training data does not capture users' behavior accurately and, thus, the level of privacy provided by the LPPM is often overestimated. To address this gap between theory and practice, we propose to use blank-slate models for LPPM design. Contrary to the hardwired approach, that assumes known users' behavior, blank-slate models learn the users' behavior from the queries to the service provider. We leverage this blank-slate approach to develop a new family of LPPMs, that we call Profile Estimation-Based LPPMs. Using real data, we empirically show that our proposal outperforms optimal state-of-the-art mechanisms designed on sporadic hardwired models. On non-sporadic location privacy scenarios, our method is only better if the usage of the location privacy service is not continuous. It is our hope that eliminating the need to bootstrap the mechanisms with training data and ensuring that the mechanisms are lightweight and easy to compute help fostering the integration of location privacy protections in deployed systems

Una nota sobre el teorema de Gleason-Kahane-Zelasko

Siendo A un álgebra conmutativa compleja, localmente convexa Hausdorff de inversión continua (no necesariamente semicompleta), se demuestra que todo hiperplano de A que solo contenga elemento singulares, es un ideal maximal de

Genetically engineered hydrogels based on elastin-like recombinamers for cardiovascular applications

Tissue engineering and regenerative medicine (TERM) is a prominent field of research that aims to repair or replace damaged tissues or organs, by the development of scaffolds with essential features, such as biocompatibility and functionality. Nowadays, recombinant polypeptides arise as promising candidates due to their tunability at the genetic level, affording exquisite control over the final physico-chemical properties and bioactivities. In particular, elastin-like recombinamers (ELRs) are genetically engineered polypeptides based on the repetition of the pentapeptide Val-Pro-Gly-X-Gly, found in the hydrophobic domains of tropoelastin, where X can be any amino acid except L-proline. These, ELRs exhibit a reversible phase transition in aqueous environments and their recombinant nature allows the inclusion of specific epitopes, such as cell adhesion, proteolytic sequences, and biologically active molecules such as growth factors. Interestingly, they can be chemically modified to obtain covalently cross-linked hydrogels through orthogonal and cytocompatible &#8220;click chemistry&#8221; reactions. The first chapter of this thesis is dedicated to the spatiotemporal control of angiogenesis, which has been proven essential for the correct integration and long-term stability of the implant. To this end, we designed a three-dimensional (3D) model consisting of a coaxial binary ELR tubular construct that displays proteolytic sequences with fast and slow cleavage kinetics towards the urokinase plasminogen activator protease on its inner and outer part respectively. The ELRs further included the universal cell-adhesion domain (RGD) and a VEGF-mimetic tethered peptide (QK) to induce angiogenesis. In vitro studies evidenced the effect of the QK peptide on endothelial cell extension and anastomosis. The subcutaneous implantation of the 3D models in mice showed a guided cell infiltration and capillary formation in the pre-designed spatiotemporal arrangement of the construct. Furthermore, the ELR hydrogels induced a mild macrophage response that resolved over time, supporting the potential integration of the resorbable scaffold within the host tissue. The second chapter study the preferential guidance of angiogenesis and neurogenesis in a spatiotemporal manner. In particular, we designed a 3D model ELR scaffold comprising two internal cylinders, with the pro-angiogenic peptide (QK) in one of them, and the neuronal cell adhesive peptide (IKVAV) in the vicinal one, both covalently tethered. In addition, these cylinders contain proteolytic sequences with fast cleavage kinetics towards the urokinase plasminogen activator enzyme and RGD cell adhesive domains. On the other hand, the outer part displays a slow-resorbable or non-protease-sensitive ELR hydrogel. In vitro studies demonstrated the effect of IKVAV epitope on neurite extension. The subcutaneous implantation of the 3D model ELR constructs in mice showed a guided cell infiltration accompanied by preferential angiogenesis or innervation on the respective QK and IKVAV containing cylinders, with a faster integration within the host tissue for the slow-resorbable scaffold. The third chapter describes the development of a ready-to-use bi-leaflet transcatheter venous valve for the treatment of chronic venous insufficiency (CVI), a leading worldwide vascular disease. For this purpose, we combined (i) ELRs, (ii) a textile mesh reinforcement and (iii) a bioabsorbable magnesium stent. Burst strength analysis demonstrated mechanical properties suitable for vascular pressures, whereas equibiaxial analysis confirmed the anisotropic performance equivalent to the native saphenous vein valves. In vitro studies identified the non-thrombogenic, minimal hemolysis and self-endothelialization properties endowed by the ELR hydrogel. The hydrodynamic testing under pulsatile conditions revealed minimal regurgitation (< 10%) and pressure drop (< 5 mmHg) in accordance with values stated for functional venous valves, and no stagnation points. Furthermore, in vitro simulated transcatheter delivery showed the ability to withstand the implantation procedure. In summary, the thesis presented herein provide new insights in the design and development of novel ELR-forming hydrogels to be used in tissue engineering and regenerative medicine applications.La ingeniería de tejidos y la medicina regenerativa (TERM) es un campo de investigación cuyo objetivo es reparar o reemplazar tejidos u órganos dañados, mediante el desarrollo de andamios biocompatibiles y funcionalizados. Hoy en día, los polipéptidos recombinantes, permiten un control exquisito sobre las propiedades fisicoquímicas y bioactividades. En particular, los elastin-like recombinamers (ELRs) son polipéptidos modificados genéticamente basados en la repetición del pentapéptido Val-Pro-Gly-X-Gly, que se encuentra en los dominios hidrófobos de la tropoelastina, donde X puede ser cualquier aminoácido excepto L-prolina. Estos ELR exhiben una transición de fase reversible en medios acuosos y su naturaleza recombinante permite la inclusión de epítopos específicos, como la adhesión celular, secuencias proteolíticas y moléculas bioactivas como factores de crecimiento. Curiosamente, pueden modificarse químicamente para obtener hidrogeles entrecruzados covalentemente a través de reacciones de "química de clic" ortogonales y citocompatibles. El primer capítulo está dedicado al control espaciotemporal de la angiogénesis, la cual es fundamental para la correcta integración y estabilidad del implante. Para ello, diseñamos un modelo tridimensional (3D) que consiste en una construcción binaria coaxial de hidrogeles de ELR, que lleva secuencias proteolíticas con cinética de escisión rápida y lenta sensibles a la proteasa del activador del plasminógeno tipo uroquinasa (uPA) en su parte interna y externa respectivamente, y un péptido mimético de VEGF (QK) anclado para inducir la angiogénesis. Los estudios in vitro evidenciaron el efecto del péptido QK sobre la extensión y anastomosis de las células endoteliales. La implantación subcutánea del modelo 3D en ratones mostró una infiltración celular guiada. Además, los hidrogeles ELR indujeron una respuesta leve de macrófagos que se resolvió con el tiempo, lo que respalda la integración de estos andamios reabsorbibles. El segundo capítulo estudia la orientación preferencial de la angiogénesis y la neurogénesis de manera espaciotemporal. En particular, diseñamos un modelo 3D de ELR que comprende dos cilindros internos, con el péptido proangiogénico (QK) en uno de ellos, y el péptido adhesivo de células neuronales (IKVAV) en el vecinal, ambos unidos covalentemente. Además, estos cilindros contienen secuencias proteolíticas con una cinética de escisión rápida frente a la enzima uPa y los dominios adhesivos RGD. Por otro lado, la parte exterior presenta un hidrogel ELR de reabsorción lenta o no sensible a las proteasas. Los estudios in vitro demostraron el efecto del epítopo IKVAV sobre la extensión de axones. La implantación subcutánea de las construcciones en ratones mostró una infiltración celular guiada acompañada de angiogénesis o inervación preferencial en los respectivos, con una integración más rápida dentro del tejido hospedador para el andamio con reabsorción lenta. El tercer capítulo describe el desarrollo de una válvula venosa transcatéter biválvula lista para usar para el tratamiento de la insuficiencia venosa crónica (IVC), una enfermedad vascular predominante en todo el mundo. Para ello, combinamos (i) ELR, (ii) un refuerzo de malla textil y (iii) un stent de magnesio bioabsorbible. El análisis de resistencia a rotura demostró propiedades mecánicas adecuadas para las presiones vasculares, mientras que el análisis equibiaxial confirmó el rendimiento anisotrópico equivalente a las válvulas de vena safena nativa. Los estudios in vitro identificaron las propiedades no trombogénicas, de hemólisis mínima y de autoendotelización que otorga el hidrogel ELR. Las pruebas hidrodinámicas en condiciones pulsátiles revelaron regurgitación mínima (< 10 %) y caída de presión (< 5 mmHg) de acuerdo con los valores establecidos para válvulas venosas funcionales y sin puntos de estancamiento. Además, el suministro transcatéter simulado in vitro mostró la capacidad de soportar el procedimiento de implantación. En resumen, la tesis presentada proporciona nuevos conocimientos en el diseño y desarrollo de nuevos hidrogeles ELR para su uso en ingeniería de tejidos y medicina regenerativa.Escuela de DoctoradoDoctorado en Físic