Tumorigenesis is the result of uncontrolled cell growth due to the deregulation of cell cycle checkpoints 1. Period 2 (Per2) is a tumor suppressor that oscillate in expression in a 24-hour cycle 2, 3. Here, we show that Per2 interacts with the tumor suppressor protein p53. Both G1 and G2 checkpoint pathways involve a p53 dependent pathway which can trigger the cell to go through cell arrest or programmed cell death4. Understanding all the mitigating factors involved in regulating cell cycle progression under DNA damage can offer a better idea in how cells become immortal. Initially discovered through screening of a human liver cDNA library, the novel interaction between p53-Per2 was further documented using co-precipitation. Interestingly, under genotoxic stress conditions, p53 and Per2 were not found to bind which leads us to suspect that Per2 does not affect active p53 which may possibly be due to post translational modifications of its active state. Furthermore we investigated p53's ability to act as a transcription factor in the presence of Per2, showing that the Per2-p53 complex prevents p53 from binding to DNA. This implies that the tetramerization of p53 may also be another factor in Per2's ability to bind to p53. A truncated p53 lacking the last 30 amino acids that theoretically increase p53's ability to form a tetramer showed a drastic reduction in binding to Per2 5, 6. On the other hand, p53 lacking the tetramerization domain showed binding similar to wildtype. Consequently we speculate that the ability of Per2 to modulate p53 and act as a tumor suppressor protein may be dependent on either the post translational modifications of p53 or its oligomeric state. / Master of Science

This dissertation investigates the work of Ogata Kōrin (1658–1716), one of the most idiosyncratic artists of Japan’s early modern period. By employing aspects of literature and theater, as well as a focus on Kōrin’s experimentations with the effects of style, materials, and artistic media, I elucidate how his oeuvre is characterized by a continuous strive to test the faculties of painting. Following a chronological approach, the four chapters of the dissertation trace Kōrin’s life and work from his early steps as a painter to the collaboration with his brother Kenzan (1663–1743) during his final years. The chapters are framed by an introduction, a conclusion, and an appendix. The first chapter focusses on Kōrin’s earliest works: two hanging scrolls depicting the medieval poet Sōgi (1421–1502) and Hotei Playing Kemari, as well as a pair of screens entitled Poetic Meanings of the Twelve Months. These works reveal Kōrin’s intellectual indebtedness to late medieval culture and the imperial court. Kōrin’s initial engagement in the arts occurred alongside his first confrontation with medieval ink modes, which laid the foundations for Kōrin’s lifelong understanding of that material. Numerous contemporary sources testify to Kōrin’s passion for the Noh theater. This little-studied, formative period of Kōrin’s life established his aesthetic sensibilities and is thus critical for understanding his art, a connection examined in the second chapter. Kōrin’s perennial engagement with Noh put him in contact with high-level aristocrats, such as the Nijō family, as well as upper-tier clergy at the temples Daigoji and Nishi Honganji. The theater also provides a possible reading of key works by Kōrin, such as his screen painting Irises. The third and fourth chapters explore Kōrin’s diversified dialogue with the material qualities of ink. The third chapter surveys his appropriation of a particular technique, tarashikomi, first championed by Tawaraya Sōtatsu (d. ca. 1640). I propose that Kōrin turned to tarashikomi as he prepared to leave his native Kyoto for Edo, where he was active for around five years. The chapter argues that Kōrin used tarashikomi, a painting method associated with Kyoto culture, to solicit clients in the shogunal capital of Edo. The last chapter is devoted to Kōrin’s collaboration with Kenzan. From the 1710s onward, the brothers created numerous examples of sabi-e, works in iron oxide on square ceramic vessels that emulate the techniques and visuality of paintings in ink. This unprecedented expansion of the boundaries of one medium to envelop another resulted in approximations of traditional ink paintings in ceramics. In the process, Kōrin expanded the paradigm of ink to include an entirely new material component. The appendix includes the first complete English-language translation of the collection of extant Edo-period letters and other documents by and about Kōrin that are contained in the Konishi Archives, held at the Kyoto National Museum, the Osaka Municipal Museum, and various other collections in Japan.

The modern plate tectonic paradigm provides a predictive model to understand what mediates dynamic processes at both plate margins and intraplate settings. At some locations on the Earth, the geological record provides evidence of apparent violations of this theoretical framework. In this dissertation, I examine a region on the rifted continental margin of Eastern North America, where at least four distinct episodes of magmatism occurred (in the Late Triassic, Early Jurassic, Early Cretaceous) since the onset of rifting and ultimate breakup of the supercontinent Pangea. It also coincides with a present-day low seismic velocity anomaly in the upper mantle. No other region on the Eastern North American Margin has a record of such anomalous dynamic processes occurring and persisting for more than 200 Myr. In this dissertation, I primarily use zircon U-Pb geochronology to establish the basic chronological framework in which magmatic and magmatic-hydrothermal systems in this region existed and persisted, establishing the temporal parameter space in which it will be possible to test geodynamic mechanisms for their formation. In Chapter 2, I use ultra-high precision zircon U-Pb geochronology via Chemical Abrasion-Isotope Dilution-Thermal Ionization Mass Spectrometry (CA-ID-TIMS) to test whether the onset of magmatism in the largest igneous body in this region (the White Mountain Batholith) is linked to the eruption of the vast flood basalts within the Central Atlantic Magmatic Province (CAMP) and whether its apparent duration is indeed > 50 Myr, as previous workers using whole rock K-Ar and mineral Ar-Ar geochronologic methods suggest. My work uncovered a previously unknown episode of rift-related magmatism in the region that precedes the both the CAMP and the emplacement of the White Mountain Batholith by 3 – 5 Myr. In Chapter 3, I use a combination of high-precision zircon U-Pb geochronology and absolute plate motion models to test whether the Cretaceous igneous province in this region resulted from hot spot magmatism as North America moved over the purported Great Meteor Hotspot. These results cannot falsify the hotspot hypothesis and the new zircon U-Pb ages therefore provide the best available chronological constraints for one of the longest-lived hot spot tracks on the Earth. In Chapter 4, motivated by the confirmation of age discrepancies between low- and intermediate-temperature chronometers and the zircon U-Pb ages presented in Chapter 2, I use a combination of both CA-ID-TIMS and LA-ICP-MS zircon U-Pb geochronologic techniques to place constraints on the timing and duration of magmatism for the Late Triassic-Early Jurassic province. The results of this chapter demonstrate that the magmatism of the White Mountain Magma Series occurs in discrete pulses through much of the Jurassic. Together with zircon Hf isotopic analyses from select samples, I synthesize these age results and construct a hypothesis testing framework in which it will be possible for future investigators to unravel the geodynamic complexities in this region. I provide recommendations for future work and emphasize the need for unified approaches coupling geochronology, geochemistry, and geophysics, to test the range of possible mechanisms responsible for these episodes of anomalous tectono-magmatic activity.

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Latium Vetus is accepted as having possessed an urban status by the archaic period. The evolution towards this status depended upon various factors operating through centuries. From an initial stage in which the region was composed of insular settlements, the first step towards urbanisation was nucleation of settlement. This was a federal grouping of small, self-governing kin units. Such were the curiae of history; their individualism is emphasised in the topography of the cemeteries. They are revealed in the remnants of early law operating along the lines of reciprocity and collusion. This nucleation was probably a result of demographic pressures; trade and technological innovation may also be considered contributory factors. Certainly these latter emerged as conditioning elements within the development of such communities. The separate units within the settlements practised an individual prestige-goods economy. Their powers were separate from those of the community as a whole. Such powers had to be curbed as the role of manufacture and trade increased. Thus the central, 'state' power grew, as may be seen in legal and historical developments. The aristocracies which had emerged had proved a destabilising factor in the state, for they maintained economic and sociopolitical practices which artificially supported secondary activities and separatist influences. As society became more complex, so the kin basis upon which it was founded proved inadequate. Changes in the demographic constitution of the community, overly competitive economic practice and increasing functional differentiation caused the creation of a public domain, one witnessed in various ways in the source material. Urbanisation was the end-result of the functioning of a prestige-goods economy in a society formed of distinctive groups prior to the initiation of large scale trade and manufacture. The competition inherent within such a society led ultimately to the unity of the urban system.

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In order to understand past human behavior, it is necessary to identify and explain variability in the cultural materials resulting from this behavior. Chipped stone artifacts are the most ubiquitous cultural materials from the Middle Paleolithic. However, the interpretation of variability in these artifacts has been difficult. To address this problem, morphological variability in 1,146 Middle Paleolithic chipped stone tools, from four sites in the Iberian Peninsula, is examined in detail. This study differs from other analyses of Middle Paleolithic artifacts in emphasizing a quantitative investigation of both continuous and discrete morphological variability at the level of tool edges. These data permit analyses of the distribution of variability at the levels of individual edges, whole pieces, and assemblages. Patterns of lithic variability are also examined in the context of early Upper Pleistocene chronology and environment and compared with a larger population of Middle Paleolithic sites in Spain and the northwestern Mediterranean as a whole. For the assemblages studied, variability in edge morphology is predominantly continuous and normally distributed. Signficantly patterned relationships between edge attributes are restricted to cases in which one attribute limits, rather than determines, the range of variability in the other. These seem primarily based in the degree to which use, resharpening, and consequent edge reduction has taken place. Additionally, a dichotomy in patterns of edge use is suggested, associated with the extensiveness of use and modification. For whole pieces, most variability mirrors that of edges, suggesting that retouched artifacts are more the result of the extent and nature of the use of their edges than planned tools for which the maker had some form of "mental template." At the level of assemblages, temporal variability is minimal, while spatial and environmental associated variability is more apparent. These results are examined in light of the three most often proposed explanations for variability in Middle Paleolithic assemblages--style, function, and diachronic change. Subsequently, other aspects of Middle Paleolithic behavior--ranging from raw material usage to settlement patterns--are examined as potential sources for the patterns of lithic variability in the assemblages studied.

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