Tsunami Hazard Assessments with Consideration of Uncertain Inputs

Tsunami hazard assessments have frequently been conducted by means of numerical models using deterministic inputs, such as the earthquake fault parameters and bathymetry. Some fault parameters of the earthquake, however, can only be estimated probabilistically for a future event. The bathymetry, on the other hand, is surveyed with an imperfect resolution and accuracy, which can lead to errors in the tsunami modeling results. Hence, tsunami assessments before an event are unavoidably uncertain. This thesis aims to describe how the uncertainties of some earthquake fault parameters and bathymetry impact the tsunami assessment uncertainties. The earthquake uncertainties are related with the assumed aleatory nature of the slip distribution and the rupture location, while the bathymetry uncertainties are associated with the lack of data in unsurveyed areas. These uncertain inputs and the corresponding tsunami response are modeled as random elements by adopting a stochastic approach. The uncertain earthquakes of this thesis consider a slip distribution modeled as an homogeneous random field and a rupture location modeled as a random vector. The bathymetry, on the other hand, is modeled as a non-homogeneous Gaussian random field, which is conditional to surveyed data. The generation of samples of the earthquake rupture location is straightforward. Conversely, the generation of samples of the slip distribution and bathymetry are rather complex. By means of a Karhunen-Loeve expansion and a translation model we propose a consistent method for the generation of samples of these uncertain inputs. Unlike other approaches, the Karhunen Loeve expansion generates consistent and accurate samples of non-rectangular random fields. The uncertainties of tsunami hazard assessments are then quantified by means of a Stochastic Reduced Order Model (SROM), which is more accurate than the classic Monte Carlo simulation for a same number of samples. The uncertainty quantification methods developed in this thesis are presented with two illustration cases. In one illustration case we study MW 8.0 earthquakes within a seismogenic region in North Chile. First, we demonstrate that our proposed method generates consistent earthquake and bathymetry samples. Second, we demonstrate that estimates of tsunami assessment uncertainties obtained with SROM are more accurate than estimates obtained with classic Monte Carlo simulations. From sensitivity analyses and comparison with records of the 2014 earthquake tsunami, we also conclude that the probability properties of the analyzed uncertain inputs and other aspects of the tsunami assessment can be relevant sources of uncertainty. In the second illustration case we perform a probabilistic tsunami hazard assessment (PTHA) which assesses earthquakes generated in the Manila Subduction Zone and tsunami responses in Hong Kong, China, and Kao Hsiung, Taiwan. First we demonstrate that our proposed methods can be combined with PTHA to account for the earthquake fault parameters and bathymetry uncertainties. Second, we demonstrate that the earthquakes recurrence model and the tsunami propagation model adopted in the PTHA constitute additional sources of uncertainty, which can be as relevant as the uncertainties of the earthquake fault parameters and bathymetry

La prueba instrumental a la luz de la Ley que crea los Tribunales de Familia

90 p.La presente memoria tratará el tema de los instrumentos dentro de la ley 19.968. Primero se estudiará que debe entenderse por instrumentos. Posteriormente se ilustrará como se compatibilizan principios como la inmediación, la oralidad, entre otros, con la incorporación y valoración de dichos instrumentos.- Consecutivamente, se analizará que instrumentos pueden incorporarse al juicio ordinario de familia, la forma de incorporarlos, si estos pueden ser objetados o no y el valor probatorio de estos. Por ultimo, se estudiará si medios de pruebas como películas, fotografías, etc, se asemejan o no a los instrumentos.- Con todo, el objetivo que se persigue es conocer al instrumento dentro de la ley 19.968 y otorgar una guía práctica para efectos de compatibilizar un procedimiento oral con la incorporación de esta prueba. Este tema se desarrollará a través de una investigación jurídico formal, usando la técnica documental y empleando un enfoque descriptivo y comparativo

Baseline and time-updated factors in preclinical development of anionic dendrimers as successful anti-HIV-1 vaginal microbicides

Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV-1 transmission. This fact demonstrates the importance and the potential of these molecules as microbicides. Polyanionic dendrimers are highly branched nanocompounds with potent activity against HIV-1 that disturb HIV-1 entry. Herein, the most significant advancements in topical microbicide development, trying to mimic the real-life conditions as closely as possible, are discussed. This review also provides the preclinical assays that anionic dendrimers have passed as microbicides because they can improve current antiviral treatments' efficacy.This work has been (partially) funded by the RD16/0025/0019 projects as part of Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (2013–2016) and cofinanced by Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigacion Sanitaria (FIS) (grant no. PI16/01863) and EPIICAL project. COST CA17140 Cancer Nanomedicine-“From the Bench to Bedside.” This work has also been supported by the Ministry of Economy and Competitiveness #CGL2013-40564-R and Gordon and Betty Moore Foundation grant no. 5334. This work was also funded by research grants from ISCIII (grant numbers PI20CIII/00004, and RD16CIII/0002/0002) to Salvador Resino. The study was also funded by the Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CB21/13/00044). DS-C is a “Sara Borrell” researcher from ISCIII (grant no. CD20CIII/00001).S

La cultura profesional de los docentes en enseñanza secundaria: Un estudio biográfico.

This work discusses the "voices" of teachers working "at the chalk face." We are interested in learning what teachers think and how they behave. Therefore, we conducted our research about their working conditions. We also developed teachers" professional biographies to learn how these educators construct concepts and practices related to their profession and what constitutes their "professional culture". We understand that thie professional culture characterizes teachers" professional frameworks and choices; therefore, any attempt to successfully promote an educational reform, must understand and pay attention to the "professional culture."Este trabajo trata sobre las "voces" de los profesores que trabajan "a pie de obra". Nos interesa aprender qué piensan los profesores y cómo se comportan. Para ello se ha llevado a cabo una investigación en sus propios contextos de trabajo. De este modo, elaboramos sus biografías profesionales para aprender como han ido construyendo estos conceptos y prácticas profesionales y, de este modo, aprender qué es lo que constituye su "cultura profesional". Entendemos que es esta cultura profesional la que determina las opciones de los profesores que caracteriza su estructura profesional y por tanto, cualquier intento de afrontar una reforma educativa necesariamente tiene que atender y entender estas estructuras

The Role of RANK-Ligand Inhibition in Cancer: The Story of Denosumab

The bone is a very common site of metastasis in patients with advanced cancer. Skeletal metastases are most common in breast and prostate cancer, but virtually any advanced cancer may disseminate to the bone. On the basis of recent advances in the understanding of bone remodeling processes, denosumab, a fully human monoclonal antibody against RANK-L, has been developed. Phase III clinical trials have demonstrated that denosumab is well tolerated and effective in the treatment of bone loss and prevention of skeletal-related events in patients with bone metastases

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN