This master’s thesis presents language community information, a descriptive grammatical sketch and analysis of structures in maqlaqsyals (Klamath-Modoc), a severely endangered isolate language traditionally spoken in present-day southern Oregon and northern California. The basis for this thesis is data from descriptive grammars from Gatschet (1890) and Barker (1964) as well as further linguistic and academic literature surrounding maqlaqsyals. This thesis is important because there is limited literature on maqlaqsyals that is accessible to the language community and this thesis fills the literature gap. This thesis is an example in practice of linguistic sovereignty. This thesis provides accessible linguistic resources written by an Indigenous community member asserting local control. Additionally, this thesis is crucial because children are on longer learning maqlaqsyals as a first language. Second language speakers must become more knowledgeable of language structure in order to converse with other speakers, setting a future environment in which children can be taught maqlaqsyals as a first language.

This thesis assesses climate change during the Hypsithermal Climatic Interval through the analysis of freshwater mussel remains from archaeological sites in Eastern North America. Modern climate data was used as a model to test the mosaic consequences of climate change. Freshwater mussels: can be used as indicators of precipitation by examining changes in overall size through time: larger mussels are found in larger streams, while smaller mussels are found in smaller streams. This study combines morphometric and isotopic data from archaeological freshwater mussels at Modoc Rock Shelter, Watson Brake, Plum Creek, Owens site, and Landerneau mounds to assess past climatic conditions. At Modoc Rock Shelter, oxygen isotopic data corroborate morphometric data and show that climate was fluctuating with a period of stability at the onset of the Hypsithermal. The oxygen isotopic data sets from the Louisiana sites show that the mid-Holocene was much warmer than the late-Holocene.

The recent emergence of a number of new viral diseases as well as the re-emergence of tuberculosis (TB), indicate an urgent need for new drugs against viral and bacterial infections. Coronavirus nsp1 has been shown to induce suppression of host gene expression and interfere with host immune response. However, the mechanism behind this is currently unknown. Here we present the first nsp1 structure from an alphacoronavirus, Transmissible gastroenteritis virus (TGEV) nsp1. Contrary to previous speculation, the TGEV nsp1 structure clearly shows that alpha- and betacoronavirus nsp1s have a common evolutionary origin. However, differences in conservation, shape and surface electrostatics indicate that the mechanism for nsp1-induced suppression of host mRNA translation is likely to be different in the alpha- and betacoronavirus genera. The Modoc virus is a neuroinvasive rodent virus with similar pathology as flavivirus encephalitis in humans. The flaviviral methyltransferase catalyses the two methylations required to complete 5´ mRNA capping, essential for mRNA stability and translation. The structure of the Modoc NS5 methyltransferase domain was determined in complex with its cofactor S-adenosyl-L-methionine. The observed methyltransferase conservation between Modoc and other flaviviral branches, indicates that it may be possible to identify drugs that target a range of flaviviruses and supports the use of Modoc virus as a model for general flaviviral studies. 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is part of the methylerythritol phosphate (MEP) pathway that produces essential precursors for isoprenoid biosynthesis. This pathway is used by a number of pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum, but it is not present in humans. Using a structure-based approach, we designed a number of MtDXR inhibitors, including a novel fosmidomycin-analogue that exhibited improved activity against P.falciparum in an in vitro blood cell growth assay. The approach also allowed the first design of an inhibitor that bridge both DXR substrate and co-factor binding sites, providing a stepping-stone for further optimization.

Water allocation in the upper Klamath Basin of Oregon and California has been challenging. Irrigators have increasingly turned to groundwater to make up for surface water shortages because of shifts in allocation toward in-stream flows for Endangered Species Act listed fishes. The largest increase in groundwater pumping has been in and around the Bureau of Reclamation's Klamath Irrigation Project, which includes the Tule Lake subbasin in the southern part of the upper Klamath Basin. Previous groundwater flow model simulations indicate that water level declines from pumping may result in decreased flow to agricultural drains in the Tule Lake subbasin. Agricultural drains on the Klamath Project are an important source of water for downstream irrigators and for the Tule Lake and Lower Klamath Lake National Wildlife Refuges. To better assess the impact of increased pumping on drain flow and on the water balance of the groundwater system, flow data from agricultural drains were evaluated to investigate the changes that have taken place in groundwater discharge to drains since pumping volumes increased. Additionally, a fine-grid groundwater model of the Tule Lake subbasin was developed based on the existing regional flow model. The fine-grid model has sufficient vertical and horizontal resolution to simulate vertical head gradients, takes advantage of time-series data from 38 observation wells for model calibration, and allows agricultural drains to be more explicitly represented. Results of the drain flow analysis show that the groundwater discharge to agricultural drains has decreased by approximately 4000 hectare-meters from the 1997-2000 average discharge. Most of this decrease takes place in the northern and southeastern portions of the subbasin. Results of the groundwater model show that the initial source of water to wells is groundwater storage. By 2006, approximately 56% of the water from wells is sourced from agricultural drains.