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Structure-Activity Relationship Studies of Diamino-Substituted Kinase Inhibitors Targeting DYRK1A and WNT Signaling Pathway
No full textMedicinal chemistry is an interdisciplinary field that integrates chemistry, biology, and pharmacology to design and optimize small-molecule therapeutics with improved efficacy and safety. This thesis focuses on the rational design, synthesis, and biological evaluation of kinase inhibitors targeting dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and Wnt/?-catenin–associated kinases, which are implicated in the pathogenesis of Alzheimer’s disease (AD) and colorectal cancer (CRC), respectively. Building upon established imidazo[4,5-b]pyridine and quinazoline scaffolds developed within the Hulme research group, systematic structure–activity relationship (SAR) studies were conducted to probe the impact of targeted modifications in three key regions of the scaffold: the lysine-binding region (Region A), the hinge-binding region (Region B), and the solvent-exposed region (Region C). A central objective of this work was to investigate the effect of introducing a 2,6-diaminopyridine motif in Region A to enhance hydrogen-bonding interactions within the kinase active site. Incorporation of this diamino moiety led to significant improvements in DYRK1A binding affinity, metabolic stability, and intrinsic clearance, as demonstrated by compounds DYR1125, DYR1149, DYR1123, and DYR1141. These gains, however, were accompanied by reductions in kinetic solubility and, in some cases, oral bioavailability, highlighting critical trade-offs in scaffold optimization. Additional modifications in Region C revealed pronounced sensitivity of biological activity to steric and electronic effects, particularly in glioblastoma (GBM) cell lines and Wnt signaling assays relevant to CRC. Notably, chloro-substituted analogues exhibited the highest antiproliferative potency, while bioisosteric substitutions produced predictable changes in activity. Biological activity, ADME, and pharmacokinetic profiles were evaluated through collaborations with Eurofins Discovery, the University of Dundee, the University of Arizona, and Pharmaron. Collectively, these studies provide valuable insight into the balance between potency, selectivity, and drug-like properties, and establish a robust foundation for the continued development of multi-targeted kinase inhibitors for neurodegenerative and oncological indications.Release after 01/20/202
Surveying the Growth of a Mycenaean State: A Reassessment of Pylian Expansion in Late Bronze Age Messenia
No full textThis thesis reassesses the nature and timeline of the expansion of the Kingdom of Pylos in Messenia during the Late Bronze Age. Evidence from Linear B documents, excavations, and regional survey projects has provided substantial information about the administration and economy of the Pylian state during the height of its power at the end of the LH IIIB period, but the nature and timeline of its growth from a single settlement to the palatial capital of Messenia is not as fully understood. Messenian survey data are used here to catalogue, map, and analyze Mycenaean settlements in the region for the LH I-II, LH IIIA-B, and LH IIIC periods. Changes to settlement patterns that are indicative of Pylian expansion are identified through a combination of traditional and novel methods. These changes are then considered along regional lines, from which three distinct waves of Pylian expansion in Messenia during the Late Bronze Age are shown
Arizona Seasonal Passes for 4-H Large Livestock Projects
No full textSeasonal Passes are essential for tracking the movement of exhibition livestock and protecting animal health statewide. The Arizona Department of Agriculture (AZDA) requires all Arizona residents who exhibit livestock at shows or the fair to possess a Seasonal Pass
Precambrian Geologic Map of the Bradshaw Mountains, Prescott 7.5’ Quadrangle, Central Arizona v. 2.0
No full textThis report summarizes a collection of Precambrian geologic maps of the Bradshaw Mountains completed by Philip Anderson and including a foreword by Steven Reynolds, Michael Conway, Julia Johnson, Michael Doe, and Nyal Neimut, written in 2017. The original map is included along with the report. Other geologic maps from the Anderson collection preserved as part of this effort are published as DGM-282, DGM-284, DGM-285, DGM-286, DGM-287, DGM-288, DGM-290, and DGM-291. Note that not all maps from the original Anderson report were revised. The report is part of a digital republication of one geologic map within this collection, originally created 1975-1984 by the Arizona Geological Survey with financial support from the U.S. Geological Survey. Preparation for republication was conducted by students from the University of Arizona with financial support from the National Geological and Geophysical Data Preservation Program, award number G24AP00258 and included the production of a new GIS geodatabase and a revised map layout. The following text report has not been altered and remains identical to the 1975-1984 original, but there may be situations where unit names, ages, symbology, or other geologic information contained within this report do not match the information presented in the new map layout of the GIS geodatabase.Documents in the AZGS Documents Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]
Soil Health: Decomposition of Organic Materials and Nutrient Mineralization
No full textThis article, published in the VegIPM Newsletter (Vol. 17, No. 1), explains how organic material decomposition and nutrient mineralization influence soil health and nutrient availability in desert crop systems.Documents in the Arizona Pest Management Center collection are made available by the Arizona Pest Management Center (APMC) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact https://acis.cals.arizona.edu/about-us/arizona-pest-management-center
36 - for the children who rot away, slowly
No full textDanielle P. Williams reading poems from Chamorrita SongThese recordings are made available by the University of Arizona Press and University of Arizona Libraries. If you have questions about this title, please contact the UA Press at http://www.uapress.arizona.edu/
08 - competing with myself
No full textDanielle P. Williams reading poems from Chamorrita SongThese recordings are made available by the University of Arizona Press and University of Arizona Libraries. If you have questions about this title, please contact the UA Press at http://www.uapress.arizona.edu/
Designing a Virtual XR Farming System: Five Activities for Beginners of Augmented Reality and Virtual Reality
No full textRepresenting the “T” in STEM, these five lessons combine agriculture design with augmented and virtual reality tools. By using extended reality (XR), the activities make emerging technologies more accessible for classrooms, school projects, or hands-on exploration
Mineral Resources of Cochise County, Arizona
No full textCochise County is situated in southeasternmost Arizona, sharing a border with New Mexico to the east and Mexico to the south (Plate 1). The county contains a rich history of metallic mining (e.g., the historic mines of Bisbee and Tombstone) but currently has only one active mining operation (i.e., the Johnson Camp mine operated by Gunnison Copper) (Gunnison Copper, 2026; Plonka and Richardson, 2025). Situated in the metal-rich Basin and Range Physiographic Province, Cochise County is host to numerous ore deposit types (e.g., porphyry, skarn, carbonate replacement, lode, epithermal, and more) and diverse associated commodities. Given the significant mineralization and potential for undiscovered critical and noncritical mineral resources in Cochise County, this region has a clear need for compilation and synthesis of geologic and mineral data into a single report to provide land users and policymakers with the requisite details to make informed decisions.
The purpose of this report is to provide a single review publication on the mineral resources of Cochise County to interested members of the general public and the geologic community. The sharing of past mining and exploration data, even in summarized form, is a significant factor in encouraging near-term exploration and bringing resource assessment forward in time to allow for careful consideration of all factors involving mining and resource extraction. This review publication contains brief summaries of each of the important mining districts of Cochise County and an associated map plate (Plate 1) with key mine/prospect locations that are addressed in the text and/or were important historic metal producers. Mining district summaries are generally organized into the following subsections: Location and History, Geologic Setting, Mineral Deposits, and Exploration Overview. Some of the less explored districts are summarized in a single District Overview section.
The reader should be aware of a few complementary resources that may aid in further understanding of the geology of Cochise County and its mineral resources. First, the U.S. Geological Survey recently published a new high resolution airborne magnetic and radiometric geophysical survey of the Arizona Porphyry Copper Belt, covering all of Cochise County (Scheirer et al., 2025). As many of the known resources in the county are exposed in uplifted mountain ranges, geophysical data will be important for moving exploration forward, especially in adjacent basins with sedimentary cover. Additionally, the Arizona Geological Survey Mining Info website hosts numerous historical mining reports, maps, drill logs, assays and more from donated mining collections that are not elsewhere available (AZGS Mining Files, 2026). The reader is encouraged to peruse this resource for additional information on each of the mining districts discussed.Documents in the AZGS Documents Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]
Precambrian Geologic Map of the Bradshaw Mountains, Crown King 7.5’ Quadrangle, Central Arizona v. 2.0
No full textThis report summarizes a collection of Precambrian geologic maps of the Bradshaw Mountains completed by Philip Anderson and including a foreword by Steven Reynolds, Michael Conway, Julia Johnson, Michael Doe, and Nyal Neimut, written in 2017. The original map is included along with the report. Other geologic maps from the Anderson collection preserved as part of this effort are published as DGM-282, DGM-285, DGM-286, DGM-287, DGM-288, DGM-289, DGM-290, and DGM-291. Note that not all maps from the original Anderson report were revised. The report is part of a digital republication of one geologic map within this collection, originally created 1977-1984 by the Arizona Geological Survey with financial support from the U.S. Geological Survey. Preparation for republication was conducted by students from the University of Arizona with financial support from the National Geological and Geophysical Data Preservation Program, award number G24AP00258 and included the production of a new GIS geodatabase and a revised map layout. The following text report has not been altered and remains identical to the 1977-1984 original, but there may be situations where unit names, ages, symbology, or other geologic information contained within this report do not match the information presented in the new map layout of the GIS geodatabase.Documents in the AZGS Documents Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]