Who Was the Man in Mexico? The Degree to Which the Mexican State Enjoyed Autonomy and Sovereignty With Respect to Its National and International Relationships From 1958 to 1964

Senior Project submitted to The Division of Social Studies of Bard College

The Chiloé Mw 7.6 earthquake of 25 December 2016 in Southern Chile and its relation to the Mw 9.5 1960 Valdivia earthquake

On 25 December 2016, a Mw 7.6 earthquake broke a portion of the Southern Chilean subduction zone south of Chiloé Island, located in the central part of the Mw 9.5 1960 Valdivia earthquake. This region is characterized by repeated earthquakes in 1960 and historical times with very sparse interseismic activity due to the subduction of a young (~15 Ma), and therefore hot, oceanic plate. We estimate the co-seismic slip distribution based on a kinematic finite fault source model, and through joint inversion of teleseismic body waves and strong motion data. The coseismic slip model yields a total seismic moment of 3.94×1020 Nm that occurred over ~30 s, with the rupture propagating mainly downdip, reaching a peak-slip of ~4.2 m. Regional moment tensor inversion of stronger aftershocks reveals thrust type faulting at depths of the plate interface. The fore- and aftershock seismicity is mostly related to the subduction interface with sparse seismicity in the overriding crust. The 2016 Chiloé event broke a region with increased locking and most likely broke an asperity of the 1960 earthquake. The updip limit of the main event, aftershocks, foreshocks and interseismic activity are spatially similar, located ~15 km offshore and parallel to Chiloé Islands west coast. The coseismic slip model of the 2016 Chiloé earthquake suggests a peak slip of 4.2 m that locally exceeds the 3.38 m slip deficit that has accumulated since 1960. Therefore, the 2016 Chiloé earthquake possibly released strain that has built up prior to the 1960 Valdivia earthquake

Uncovering human transcription factor interactions associated with genetic variants, novel DNA motifs, and repetitive elements using enhanced yeast one-hybrid assays

Identifying transcription factor (TF) binding to noncoding variants, uncharacterized DNA motifs, and repetitive genomic elements has been difficult due to technical and computational challenges. Indeed, current experimental methods such as chromatin immunoprecipitation are capable of only testing one TF at a time and motif prediction algorithms often lead to false positive and false negative predictions. Here, we address these limitations by developing two approaches based on enhanced yeast one-hybrid assays. The first approach allows to interrogate the binding of >1,000 human TFs to single nucleotide variant alleles, short insertions and deletions (indels), and novel DNA motifs; while the second approach allows for the identification of TFs that bind to repetitive DNA elements. Using the former approach, we identified gain of TF interactions to a GG→AA mutation in the TERT promoter and an 18 bp indel in the TAL1 super-enhancer, both of which are associated with cancer, and identified the TFs that bind to three uncharacterized DNA motifs identified by the ENCODE Project in footprinting assays. Using the latter approach, we detected the binding of 75 TFs to the highly repetitive Alu elements. We anticipate that these approaches will expand our capabilities to study genetic variation and under-characterized genomic regions.https://doi.org/10.1101/459305First author draf

Transcriptional regulation landscape in health and disease

Transcription factors (TFs) control gene expression by binding to highly specific DNA sequences in gene regulatory regions. This TF binding is central to control myriad biological processes. Indeed, transcriptional dysregulation has been associated with many diseases such as autoimmune diseases and cancer. In this thesis, I studied the transcriptional regulation of cytokines and gene transcriptional dysregulation in cancer. Cytokines are small proteins produced by immune cells that play a key role in the development of the immune system and response to pathogens and inflammation. I mined three decades of research and developed a user-friendly database, CytReg, containing 843 human and 647 mouse interactions between TFs and cytokines. I analyzed CytReg and integrated it with phenotypic and functional datasets to provide novel insights into the general principles that govern cytokine regulation. I also predicted novel cytokine promoter-TF interactions based on cytokine co-expression patterns and motif analysis, and studied the association of cytokine transcriptional dysregulation with disease. Transcriptional dysregulation can be caused by single nucleotide variants (SNVs) affecting TF binding sites (TFBS). Therefore, I created a database of altered TFBS (aTFBS-DB) by calculating the effect (gain/loss) of all possible SNVs across the human genome for 741 TFs. I showed how the probabilities to gain or disrupt TFBSs in regulatory regions differ between the major TF families, and that cis-eQTL SNVs are more likely to perturb TFBSs than common SNVs in the human population. To further study the effect of somatic SNVs in TFBS, I used the aTFBS-DB to develop TF-aware burden test (TFABT), a novel algorithm to predict cancer driver SNVs in gene promoters. I applied the TFABT to the Pan-Cancer Analysis of Whole Genomes (PCAWG) cohort and identified 2,555 candidate driver SNVs across 20 cancer types. Further, I characterized these cancer drivers using functional and biophysical assay data from three cancer cell lines, demonstrating that most SNVs alter transcriptional activity and differentially recruit cofactors. Taken together, these studies can be used as a blueprint to study transcriptional mechanisms in specific cellular processes (i.e. cytokine expression) and the effect of transcriptional dysregulation in disease (i.e. cancer)

Elucidating the interaction of Borrelia burgdorferi OspC with phagocytes in the establishment of lyme borreliosis

Indiana University-Purdue University Indianapolis (IUPUI)Lyme disease, the most prevalent vector-borne illness in the United States, is a multisystem inflammatory disorder caused by infection with the spirochete Borrelia burgdorferi (Bb). This spirochete is maintained in nature through an enzootic cycle involving ticks and small mammals. The Bb genome encodes a large number of surface lipoproteins, many of which are expressed during mammalian infection. One of these lipoproteins is the major outer surface protein C (OspC) whose production is induced during transmission as spirochetes transition from ticks to mammals. OspC is required for Bb to establish infection in mice and has been proposed to facilitate evasion of innate immunity. However, the exact biological function of OspC remains elusive. Our studies show the ospC-deficient spirochete could not establish infection in NOD-scid IL2rγnull mice that lack B cells, T cells, NK cells, and lytic complement, whereas the wild-type spirochete was fully infectious in these mice. The ospC mutant also could not establish infection in SCID and C3H mice that were transiently neutropenic during the first 48 h post-challenge. However, depletion of F4/80+ phagocytes at the skin-site of inoculation in SCID mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted SCID mice, the ospC mutant was capable to colonize the joints and triggered neutrophilia during dissemination in a similar pattern as wild-type bacteria. We then constructed GFP-expressing Bb strains to evaluate the interaction of the ospC mutant with phagocytes. Using flow cytometry and fluorometric assay for phagocytosis, we found that phagocytosis of GFP-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 cells was significantly higher than parental wild-type Bb strains, suggesting that OspC has an anti-phagocytic property. This enhancement in phagocytosis was not mediated by MARCO and CD36 scavenger receptors and was not associated with changes in mRNA levels of TNFα, IL-1β, and IL-10. Phagocytosis assays with HL60 neutrophil-like cells showed that uptake of Bb strains was independent to OspC. Together, our findings reveal that F4/80+ phagocytes are important for clearance of the ospC mutant, and suggest that OspC promotes spirochetes' evasion of macrophages in the skin of mice during early Lyme borreliosis

Metodologia de calculo de la potencia requerida por el sistema de bombeo para la inyeccion de plastico fundido en moldes discontinuos

102 p.En este trabajo de titulación se basa en la elaboración una metodología de cálculo de la potencia requerida por el sistema de bombeo para la inyección de plástico fundido en moldes discontinuos. El resultado alcanzado fue desarrollar una metodología de calculó aplicable, para ello se estudio y analizo el funcionamiento y componentes de una maquina inyectora de plástico, además se estudio el comportamiento de un polímero, las ecuaciones que modelan su comportamiento y todo esto regido por la norma DIN SERIE 1342

La valoración de la prueba en el procedimiento aduanero de duda razonable

El presente trabajo de investigación abarca el estudio sobre la figura de la valoración de la prueba realizada en los procedimientos de duda razonable, siendo que esta investigación jurídica propone adoptar criterios de valoración probatoria que oriente a la administración aduanera en harás de velar por el respeto a un debido procedimiento. Se ha efectuado un análisis de la valoración probatoria realizada en aplicación de cada método de valoración aduanera según el acuerdo de valor de la OMC, así como los distintos documentos comerciales, bancarios y financieros que el importador presenta para acreditar el precio realmente pagado o por pagar de las mercancías a fin de determinar el valor de aduanas. Por último, se llegó a la conclusión principal de la importancia de adoptar criterios de valoración de la prueba para un mayor análisis técnico-jurídico de las pruebas ofrecidas y las consecuencias ante una incorrecta valoración de la prueba en el procedimiento Duda Razonable, impidiendo el normal desarrollo de la actividad probatoria y distorsionando el resultado de la determinación del valor en aduana, afectando el derecho a probar que tiene el importador de acreditar la transacción comercial internacional declarada en la Declaración Aduanera de Mercancías (DAM)