General Purpose Computer-Assisted Clustering and Conceptualization

We develop a computer-assisted method for the discovery of insightful conceptualizations, in the form of clusterings (i.e., partitions) of input objects. Each of the numerous fully automated methods of cluster analysis proposed in statistics, computer science, and biology optimize a different objective function. Almost all are well defined, but how to determine before the fact which one, if any, will partition a given set of objects in an “insightful” or “useful” way for a given user is unknown and difficult, if not logically impossible. We develop a metric space of partitions from all existing cluster analysis methods applied to a given dataset (along with millions of other solutions we add based on combinations of existing clusterings) and enable a user to explore and interact with it and quickly reveal or prompt useful or insightful conceptualizations. In addition, although it is uncommon to do so in unsupervised learning problems, we offer and implement evaluation designs that make our computer-assisted approach vulnerable to being proven suboptimal in specific data types. We demonstrate that our approach facilitates more efficient and insightful discovery of useful information than expert human coders or many existing fully automated methods.Governmen

Development towards commercialization of marine fish larvae feeds – Microdiets: Final FRDC report - Project 2004/258

The project specifically focused on developing formulated diets for marine fish larvae, specifically targeting more physical aspects of microdiets such as feeding methods, feed availability and particle recognition. A commercially ready microdiet formulation was developed that achieved better ingestion, digestion and survival for yellowtail kingfish than other commercially available diets. Two manufacturers of aquaculture feeds showed interested in the formulations, however neither of the companies have started producing the diet commercially

Resolving the Controversy Over the Core Radius of 47 Tucanae (NGC 104)

This paper investigates the discrepancy between recent measurements of the density profile of the globular cluster 47 Tuc that have used HST data sets. Guhathakurta et al. (1992) used pre-refurbishment WFPC1 V-band images to derive r_c = 23" +/- 2". Calzetti et al. (1993) suggested that the density profile is a superposition of two King profiles (r_c = 8" and r_c = 25") based on U-band FOC images. De Marchi et al. (1996) used deep WFPC1 U-band images to derive r_c = 12" +/- 2". Differences in the adopted cluster centers are not the cause of the discrepancy. Our independent analysis of the data used by De Marchi et al. reaches the following conclusions: (1) De Marchi et al.'s r_c ~ 12" value is spuriously low, a result of radially-varying bias in the star counts in a magnitude limited sample -- photometric errors and a steeply rising stellar luminosity function cause more stars to scatter across the limiting magnitude into the sample than out of it, especially near the cluster center where crowding effects are most severe. (2) Changing the limiting magnitude to the main sequence turnoff, away from the steep part of the luminosity function, partially alleviates the problem and results in r_c = 18". (3) Combining such a limiting magnitude with accurate photometry derived from PSF fitting, instead of the less accurate aperture photometry employed by De Marchi et al., results in a reliable measurement of the density profile which is well fit by r_c = 22" +/- 2". Archival WFPC2 data are used to derive a star list with a higher degree of completeness, greater photometric accuracy, and wider areal coverage than the WFPC1 and FOC data sets; the WFPC2-based density profile supports the above conclusions, yielding r_c = 24" +/- 1.9".Comment: 22 pages, 5 figures, 1 table; accepted for publication in PASP; see http://www.ucolick.org/~raja/hgg.tar.gz for full-resolution figure

Model-guided mutational analysis of Activation-induced cytidine deaminase (AID) to elucidate structure-function relationships

Activation-induced cytidine deaminase (AID) is a DNA mutating cytidine deaminase enzyme that is a member of the AID/ Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of cytidine deaminases, altogether consisting of 11 members in humans. AID deaminates deoxycytidine to deoxyuridine at immunoglobulin loci in activated B lymphocytes to mediate secondary antibody diversification. AID-mediated mutations have also been implicated in epigenetic reprogramming, as well as genome-wide DNA damage and chromosomal translocations that transform healthy B cells into lymphoma/leukemia. Since its discovery in 1999, a key element missing in the AID field has been the lack of a protein structure. The goal of this thesis was to solve this problem and determine how AID binds its substrate nucleic acid and how these interactions result in its physiological and aberrant activities. In chapter 2 of this thesis, we explored the role AID plays in epigenetic reprogramming through genome-demethylation. We provided a glimpse into the AID catalytic pocket structure and how AID from humans and other species target cytidine vs 5-methylcytidine. In chapter 3, we provided the first functional and breathing structure of AID using a unique computational-biochemical approach. In this work, we provided the first fine map of AID’s structure, identified the structural details of its catalytic pocket and interactions with the DNA substrate including secondary catalytic residues that are key to cytidine stabilization in the pocket, delineated two novel substrate DNA binding grooves on the surface and studied how conformational changes in the AID structure regulate its function. The work culminated in our discovery and proof that dynamic catalytic pocket closure limits AID activity. This novel catalytic pocket state which we termed the “Schrödinger’s CATalytic pocket” has since been confirmed by multiple other structural studies and represents a novel mode of enzyme activity regulation across all known nucleic acid modifying enzymes. Our work also provided a structural rationale for many of the biochemical properties of AID including its unusually low catalytic rate and atypically high nanomolar range binding affinity for its substrate DNA. In Chapter 5, we utilized these structural insights and the combined computational-biochemical approach developed in Chapter 3 to screen a large library of small molecule drug-like compounds against the catalytic pocket of AID. We have identified and functionally tested the first small molecule inhibitors that block the mutagenic activity of AID. We also demonstrated that several of these small molecules can inhibit several of AID’s tumorigenic APOBEC siblings. And finally in Chapter 6, we review several DNA/RNA binding grooves previously discovered on AID and explore their possible binding combinations. We explore how these plastic modes of binding DNA and RNA simultaneously may impact AID function. Finally, we examine proposed AID dimer models bound to DNA/RNA and examine how this may act as an additional regulatory bottleneck of enzymatic activity

Development and Testing of a Low Flame Temperature, Peroxide-Alcohol-Based Monopropellant Thruster

Recent developments in chemical propulsion for CubeSats have been directed away from high flame temperature propellants such as the ionic salts and towards cooler propellants that mitigate thermal management issues. Engineers at CU Aerospace have continued the development of a Monopropellant Propulsion Unit for CubeSats (MPUC), which burns a diluted mixture of hydrogen peroxide and alcohol called CUA MonoPropellant #10 (CMP-X). The propellant was subjected to UN classification tests and has been certified for air transport, demonstrating “little to no reactivity as an explosive in the UN Test Series 1 & 2 tests.” Recent experimental measurements demonstrate that MPUC with CMP-X operates at a flame temperature below 1000 °C, enabling its manufacture from standard stainless steels and avoiding more costly refractory metal components common with HAN-or ADN-based thrusters. Using hardware optimized for ~150 mN operation, a high-Isp test measured 180 s at 174 mN and a high-thrust test measured 450 mN at 154 s. A preliminary 1.5U design provides 1600 N-s total impulse

Evaluation of Operation IceBridge quick-look snow depth estimates on sea ice

We evaluate Operation IceBridge (OIB) ‘quick-look’ (QL) snow depth on sea ice retrievals using in situ measurements taken over immobile first-year ice (FYI) and multi-year ice (MYI) during March of 2014. Good agreement was found over undeformed FYI (-4.5 cm mean bias) with reduced agreement over deformed FYI (-6.6 cm mean bias). Over MYI, the mean bias was -5.7 cm but 54% of retrievals were discarded by the OIB retrieval process as compared to only 10% over FYI. Footprint scale analysis revealed a root mean square error (RMSE) of 6.2 cm over undeformed FYI with RMSE of 10.5 cm and 17.5 cm in the more complex deformed FYI and MYI environments. Correlation analysis was used to demonstrate contrasting retrieval uncertainty associated with spatial aggregation and ice surface roughness