Security and privacy services based on biosignals for implantable and wearable device

Mención Internacional en el título de doctorThe proliferation of wearable and implantable medical devices has given rise to an interest in developing security schemes suitable for these devices and the environment in which they operate. One area that has received much attention lately is the use of (human) biological signals as the basis for biometric authentication, identification and the generation of cryptographic keys. More concretely, in this dissertation we use the Electrocardiogram (ECG) to extract some fiducial points which are later used on crytographic protocols. The fiducial points are used to describe the points of interest which can be extracted from biological signals. Some examples of fiducials points of the ECG are P-wave, QRS complex,T-wave, R peaks or the RR-time-interval. In particular, we focus on the time difference between two consecutive heartbeats (R-peaks). These time intervals are referred to as Inter-Pulse Intervals (IPIs) and have been proven to contain entropy after applying some signal processing algorithms. This process is known as quantization algorithm. Theentropy that the heart signal has makes the ECG values an ideal candidate to generate tokens to be used on security protocols. Most of the proposed solutions in the literature rely on some questionable assumptions. For instance, it is commonly assumed that it possible to generate the same cryptographic token in at least two different devices that are sensing the same signal using the IPI of each cardiac signal without applying any synchronization algorithm; authors typically only measure the entropy of the LSB to determine whether the generated cryptographic values are random or not; authors usually pick the four LSBs assuming they are the best ones to create the best cryptographic tokens; the datasets used in these works are rather small and, therefore, possibly not significant enough, or; in general it is impossible to reproduce the experiments carried out by other researchers because the source code of such experiments is not usually available. In this Thesis, we overcome these weaknesses trying to systematically address most of the open research questions. That is why, in all the experiments carried out during this research we used a public database called PhysioNet which is available on Internet and stores a huge heart database named PhysioBank. This repository is constantly being up dated by medical researchers who share the sensitive information about patients and it also offers an open source software named PhysioToolkit which can be used to read and display these signals. All datasets we used contain ECG records obtained from a variety of real subjects with different heart-related pathologies as well as healthy people. The first chapter of this dissertation (Chapter 1) is entirely dedicated to present the research questions, introduce the main concepts used all along this document as well as settle down some medical and cryptographic definitions. Finally, the objectives that this dissertation tackles down are described together with the main motivations for this Thesis. In Chapter 2 we report the results of a large-scale statistical study to determine if heart signal is a good source of entropy. For this, we analyze 19 public datasets of heart signals from the Physionet repository, spanning electrocardiograms from multiple subjects sampled at different frequencies and lengths. We then apply both ENT and NIST STS standard battery of randomness tests to the extracted IPIs. The results we obtain through the analysis, clearly show that a short burst of bits derived from an ECG record may seem random, but large files derived from long ECG records should not be used for security purposes. In Chapter3, we carry out an análisis to check whether it is reasonable or not the assumption that two different sensors can generate the same cryptographic token. We systematically check if two sensors can agree on the same token without sharing any type of information. Similarly to other proposals, we include ECC algorithms like BCH to the token generation. We conclude that a fuzzy extractor (or another error correction technique) is not enough to correct the synchronization errors between the IPI values derived from two ECG signals captured via two sensors placed on different positions. We demonstrate that a pre-processing of the heart signal must be performed before the fuzzy extractor is applied. Going one step forward and, in order to generate the same token on different sensors, we propose a synchronization algorithm. To do so, we include a runtimemonitoralgorithm. Afterapplyingourproposedsolution,werun again the experiments with 19 public databases from the PhysioNet repository. The only constraint to pick those databases was that they need at least two measurements of heart signals (ECG1 and ECG2). As a conclusion, running the experiments, the same token can be dexix rived on different sensors in most of the tested databases if and only if a pre-processing of the heart signal is performed before extracting the tokens. In Chapter 4, we analyze the entropy of the tokens extracted from a heart signal according to the NISTSTS recommendation (i.e.,SP80090B Recommendation for the Entropy Sources Used for Random Bit Generation). We downloaded 19 databases from the Physionet public repository and analyze, in terms of min-entropy, more than 160,000 files. Finally, we propose other combinations for extracting tokens by taking 2, 3, 4 and 5 bits different than the usual four LSBs. Also, we demonstrate that the four LSB are not the best bits to be used in cryptographic applications. We offer other alternative combinations for two (e.g., 87), three (e.g., 638), four (e.g., 2638) and five (e.g., 23758) bits which are, in general, much better than taking the four LSBs from the entropy point of view. Finally, the last Chapter of this dissertation (Chapter 5) summarizes the main conclusions arisen from this PhD Thesis and introduces some open questions.Programa de Doctorado en Ciencia y Tecnología Informática por la Universidad Carlos III de MadridPresidente: Arturo Ribagorda Garnacho.- Secretario: Jorge Blasco Alis.- Vocal: Jesús García López de la Call

Allergic reactions to β-lactam antibiotics: chemical approaches for improving in vitro diagnosis

Moreover, conjugation of CLV with human serum albumin (HSA) was studied by liquid chromatography mass-spectrometry (LC/MS-MS) and a biotinylated derivative of CLV was used as tool for identification of serum proteins target of modification by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE) and peptide mass fingerprinting. By the other hand, we pursued the amplification of immunoassays detection signal. With this objective, fluorescent dendrons allowing site-specific conjugation to biomolecules and bearing 1, 2 or 8 fluorescent units were designed and synthesized, and their suitability for labeling antibodies and fluorescence amplification capacity evaluated [6]. The main conclusions of this work have been that synthesized cyclized structures derived from cefaclor and cefadroxil (Cef1 and Cef2, respectively) are specifically recognised by sIgE from patients allergic to the corresponding cephalosporin or to penicillins containing the same R1 side chain, shedding light into the mechanism involved in allergy to α-aminocephalosporins and complementing studies previously reported [7, 8]. Also, the ability of our synthetic determinants of CLV to activate basophils from patients with immediate reactions to this drug has been demonstrated to be influenced by the chemical structure and their reactivity to proteins. Clav2, coming from AD-I, activates basophils in a higher proportion of patients compared to CLV itself, and thus represents a promising structure to improve the sensitivity of in vitro diagnosis. Furthermore, a 70 Da mass structure was found to modify Lys 195 and Lys 475 of HSA, being this mass compatible with that of AD-I, which confirms that Clav2 is part of the drug-protein conjugate. Moreover, a water soluble biotinylated derivative of CLV (CLV-TEG-B) showed concentration-dependent protein haptenation capacity in vitro, and made possible the identification of HSA, haptoglobin and heavy and light chains of immunoglobulins as potential serum proteins target of modification by CLV. Finally, synthesized fluorescent dendrons G0-Cy5, G1-Cy5 and G3-Cy5 showed an increment in fluorescence with the number of fluorescent units and they were proved to be suitable for site-specific labeling of a model antibody. The labeling with G1-Cy5 dendron (2 fluorescent units) resulted to be the most suitable for immunoassays signal amplification applications, since it was found to enhance fluorescence by one order of magnitude when compared with the antibody labeled with the monovalent probe G0-Cy5 [6]. Fecha de lectura Tesis Doctoral: 30 octubre 2018.Drug hypersensitivity reactions are a significant public health problem with important consequences on patient health and healthcare costs. It has been reported that only a low percentage of initial cases suspected of allergy to antibiotics are finally confirmed [1, 2], and betalactam antibiotics (BLs) are the drugs most frequently involved [3, 4]. In vivo tests (skin test and drug provocation test) are often the first and only option for diagnosis, nevertheless they could be risky for patients. Thus, in vitro tests are a more convenient and safer alternative for diagnosis, however, a sensitive and specific detection of specific IgE (sIgE), crucial for in vitro allergy diagnosis, is difficult to achieve in cases of allergy to drugs due to the extremely low sIgE concentration present in patients serum [5]. The sensitivity of in vitro tests for diagnosing allergy to BLs depends, among other factors, on: (i) the similarity between the structure used in the assay as emulator of the antigenic determinant (AD) formed in vivo and the structure actually formed after the BL intake, which is related to the mechanisms involved in the allergic process, and (ii) the intensity of the detection signal (radioactivity, enzimatic proccess or fluorescence) at low concentrations of sIgE to drugs. The general objective of this thesis is to carry out studies directed to improve current in vitro tests for diagnosing immediate allergic reactions to BLs. More specifically, by one hand, we aimed to research, from a chemical approach, the structures recognized by sIgE for cephalosporins and clavulanic acid (CLV) since there has been an increase of cases of allergy to these BLs in the last years, due to the change in prescription patterns [1]. For this purpose, structures derived from these BLs were designed and synthesized and their immunological evaluation performed using RadioAllergoSorbent Test (RAST) or Basophil Activation Test (BAT)

Influence of Kaolinite Clay Supplementation on Growth Performance and Digestive Function in Finishing Calf-fed Holstein Steers.

Two experiments were conducted to examine the influence of kaolinite clay supplementation (0%, 1%, or 2% diet dry matter [DM] basis) on characteristics of digestion (Trial 1) and growth performance (Trial 2) in calf-fed Holstein steers fed a finishing diet. In Trial 1, 6 Holstein steers (539±15 kg) with ruminal and duodenal cannulas were used to evaluate treatment effects on characteristics of digestion. Kaolinite clay supplementation decreased total tract DM digestion (linear effect, p<0.01) without effects (p≥0.10) on site and extent of digestion of organic matter, neutral detergent fiber, starch and N, or ruminal microbial efficiency. There were no treatment effects on ruminal pH, volatile fatty acids molar proportions or estimated methane production. In Trial 2, 108 Holstein steers (132.4±5.6 kg) were used in a 308-d study to evaluate growth performance and carcass characteristics. There were no treatment effects (p>0.10) on average daily gain (ADG) and gain efficiency (ADG/dry matter intake). Kaolinite supplementation tended (linear effect, p = 0.08) to increase dietary net energy (NE) during the initial 112-d period. However, the overall (308-d) effect of supplementation dietary NE was not appreciable (p>0.20). However, due to the inertness of kaolinite, itself, the ratio of observed-to-expected dietary NE increased with kaolinite supplementation. This effect was more pronounced (linear effect, p 0.03) during the initial 224 d of the study. Overall (308 d), kaolinite supplementation tended to increase (linear effect, p = 0.07) dietary NE by 3% over expected. Kaolinite supplementation did not affect carcass weight, yield grade, longissimus area, kidney, pelvic and heart fat, and quality grade, but decreased (linear effect, p = 0.01) dressing percentage. It is concluded that kaolinite supplementation up to 2% of diet DM may enhance energetic efficiency of calf-fed Holstein steers in a manner independent of changes in characteristics of ruminal and total tract digestion

Geoenvironmental Characterization of Sulfide Mine Tailings

Spain has a long mining tradition dating from pre-historic times up to the present day. The cessation of mining activity has generated a large amount of mine wastes, most of which represent geochemical hazards. Mine tailings are watery sludge composed of medium-to-fine-grained material, resulting from grinding and mineral processing (e.g., galena, pyrite, sphalerite, and arsenopyrite). They entail both an accumulation and a potential subsequent emission source of trace elements (i.e. As, Cu, Fe, Pb, and Zn) with formation of acid mine drainage (AMD). Mineralogical and geochemical techniques (in combination with geophysical surveys and aerial photographs studies) have been jointly applied to selected mine areas. Seven mine deposits from the most important mine districts in Spain have been selected: Iberian Pyrite Belt, Cartagena-La Unión, Alcudia Valley, and Mazarrón. The main goal is focused on getting a geoenvironmental characterization as complete as possible by determining the geometry, evolution in time and composition of mine ponds, and the possible occurrence of AMD, for identifying related environmental hazards

Localization and oscillations of Majorana fermions in a two-dimensional electron gas coupled with d-wave superconductors

We study the localization and oscillation properties of the Majorana fermions that arise in a two-dimensional electron gas (2DEG) with spin-orbit coupling (SOC) and a Zeeman field coupled with a d-wave superconductor. Despite the angular dependence of the d-wave pairing, localization and oscillation properties are found to be similar to the ones seen in conventional s-wave superconductors. In addition, we study a microscopic lattice version of the previous system that can be characterized by a topological invariant. We derive its real space representation that involves nearest and next-to-nearest-neighbors pairing. Finally, we show that the emerging chiral Majorana fermions are indeed robust against static disorder. This analysis has potential applications to quantum simulations and experiments in high-T_(c) superconductors

Informe sobre el aborto

Informe elaborado por la Comisión de la Vida. Grupo de Profesores católicos de la Universidad de Córdob

Periodic analogues of the Kerr solutions: a numerical study

In recent years black hole configurations with non standard topology or with non-standard asymptotic have gained considerable attention. In this article we carry out numerical investigations aimed to find periodic coaxial configurations of co-rotating 3+1 vacuum black holes, for which existence and uniqueness has not yet been theoretically proven. The aimed configurations would extend Myers/Korotkin-Nicolai's family of non-rotating (static) coaxial arrays of black holes. We find that numerical solutions with a given value for the area A and for the angular momentum J of the horizons appear to exist only when the separation between consecutive horizons is larger than a certain critical value that depends only on A and |J|. We also establish that the solutions have the same Lewis's cylindrical asymptotic as Stockum's infinite rotating cylinders. Below the mentioned critical value the rotational energy appears to be too big to sustain a global equilibrium and a singularity shows up at a finite distance from the bulk. This phenomenon is a relative of Stockum's asymptotic's collapse, manifesting when the angular momentum (per unit of axial length) reaches a critical value compared to the mass (per unit of axial length), and that results from a transition in the Lewis's class of the cylindrical exterior solution. This remarkable phenomenon seems to be unexplored in the context of coaxial arrays of black holes. Ergospheres and other global properties are also presented in detail.Comment: 25 page