PHD Entrepreneur

presentationThe idea for this speech began when my friends and family started asking what I would do after graduating with my PhD in psychology. Folks tended to get a bit confused when I replied that my plan is to start a business. You don't need a PhD to do that! It's true. The path leading from PhD to Entrepreneur is a road-less-taken. And yet, the path is gaining both feasibility and popularity. Years from now, when historians of academia evaluate the early 2100s, they will classify me as an "early adopter" of the PhD-Entrepreneur identity. That's what I predict, anyway. The speech provides a socio-economical argument to support that prediction

Doctor of Philosophy

dissertationPupil dilation measures provide a useful index of test-taking processes. Prior research has established a simple positive relationship between pupil dilation magnitude and (i) threat levels, (ii) task difficulty levels, and (iii) working memory capacity. Surprisingly few studies have investigated the interaction of these three pupil response drivers. Do they add in a linear fashion, like separate weights on a single scale (as the "load" metaphor suggests), or is their relationship more complicated? To test of this question, I used a 2 X (2 X 3) mixed experimental design with random assignment to working memory resource depletion and nondepletion groups. These groups completed two versions of the same task, where response inhibition is required repeatedly in the depleting but is not required in the nondepleting version. Next, all subjects completed a test (90 factor-multiple judgment items) that employed two levels of difficulty (easy and difficult) and three levels of threat (safe, partially cued threat, and fully cued threat). Testtaking pupil data were collected at 60 Hz using a Tobii eye-tracker. Results indicated that levels of threat and task difficulty independently contribute to pupil response magnitude and they do not moderate one another. Apparently, the effects of difficulty and threat are not moderated by resource depletion; however, this study lacked power to detect anything less than a strong depletion effect. Results indicate that test-taking pupil responses are sensitive to testing conditions (e.g., threat and difficulty), but it remains unclear whether these responses are also sensitive to priming conditions (e.g., resource depletion)

Master of Science

thesisVery few studies have investigated the construct validity of measures of masculinity. This study analyzed multitrait multimethod matrices of male and female subscale scores from the Male Role Norms Inventory-Revised (MRNI-R), the Conformity to Masculine Norms Inventory (CMNI), and the Gender Role Conflict Scale (GRCS). Six subscales were of interest. Specifically, measures of dominance, homophobia, restrictive emotionality, nonrelational sexuality, aggression, and self reliance were given to 176 undergraduates from a large university in Utah. Subscale correlations were compared to indicate convergent and discriminant validity, as well as method effects, for each masculinity measure. Generally, the measures performed slightly better among males than females and the multidimensional structure of the CMNI was supported. Surprisingly, results indicated modest or poor validity among many of the subscales. These results were explained in terms of a construct confound on the GRCS, a very high method effect for the MRNI-R, and inconsistency between constructs and definitions among the measures. Finally, a preliminary content analysis of masculinity scales generated hypotheses about convergence between masculinity science and other social science disciplines. Limitations of this study and recommendations for future research were noted

Computational Design of Affinity and Specificity at Protein-Protein Interfaces

The computer-based design of protein-protein interactions is a rigorous test of our understanding of molecular recognition and an attractive approach for creating novel tools for cell and molecular research. Considerable attention has been placed on redesigning the affinity and specificity of naturally occurring interactions. Several studies have shown that reducing the desolvation costs for binding while preserving shape complimentarity and hydrogen bonding is an effective strategy for improving binding affinities. In favorable cases specificity has been designed by focusing only on interactions with the target protein, while in cases with closely related off-target proteins, it has been necessary to explicitly disfavor unwanted binding partners. The rational design of protein-protein interactions from scratch is still an unsolved problem, but recent developments in flexible backbone design and energy functions hold promise for the future

Go in! Go out! Inducible control of nuclear localization

Cells have evolved a variety of mechanisms to regulate the enormous complexity of processes taking place inside them. One mechanism consists in tightly controlling the localization of macromolecules, keeping them away from their place of action until needed. Since a large fraction of the cellular response to external stimuli is mediated by gene expression, it is not surprising that transcriptional regulators are often subject to stimulus-induced nuclear import or export. Here we review recent methods in chemical biology and optogenetics for controlling the nuclear localization of proteins of interest inside living cells. These methods allow researchers to regulate protein activity with exquisite spatiotemporal control, and open up new possibilities for studying the roles of proteins in a broad array of cellular processes and biological functions

Probing the minimal determinants of zinc binding with computational protein design

Structure-based protein design tests our understanding of the minimal determinants of protein structure and function. Previous studies have demonstrated that placing zinc binding amino acids (His, Glu, Asp or Cys) near each other in a folded protein in an arrangement predicted to be tetrahedral is often sufficient to achieve binding to zinc. However, few designs have been characterized with high-resolution structures. Here, we use X-ray crystallography, binding studies and mutation analysis to evaluate three alternative strategies for designing zinc binding sites with the molecular modeling program Rosetta. While several of the designs were observed to bind zinc, crystal structures of two designs reveal binding configurations that differ from the design model. In both cases, the modeling did not accurately capture the presence or absence of second-shell hydrogen bonds critical in determining binding-site structure. Efforts to more explicitly design second-shell hydrogen bonds were largely unsuccessful as evidenced by mutation analysis and low expression of proteins engineered with extensive primary and secondary networks. Our results suggest that improved methods for designing interaction networks will be needed for creating metal binding sites with high accuracy

RosettaDesign server for protein design

The RosettaDesign server identifies low energy amino acid sequences for target protein structures (). The client provides the backbone coordinates of the target structure and specifies which residues to design. The server returns to the client the sequences, coordinates and energies of the designed proteins. The simulations are performed using the design module of the Rosetta program (RosettaDesign). RosettaDesign uses Monte Carlo optimization with simulated annealing to search for amino acids that pack well on the target structure and satisfy hydrogen bonding potential. RosettaDesign has been experimentally validated and has been used previously to stabilize naturally occurring proteins and design a novel protein structure

Redesigning the NEDD8 Pathway with a Bacterial Genetic Screen for Ubiquitin-Like Molecule Transfer

Pathways of ubiquitin-like (UBL) molecule transfer regulate a myriad of cellular cascades. Here we report a high-throughput assay that correlates catalytic human-NEDD8 transfer to bacterial survival. The assay was utilized to screen mutant NEDD8 and NEDD8-activating enzyme (NAE) libraries to engineer a more stable NEDD8 and redesign the NEDD8-NAE interface. This approach will be useful in understanding the specificities underlying UBL pathways

Computational design of affinity and specificity at protein–protein interfaces

The computer-based design of protein-protein interactions is a rigorous test of our understanding of molecular recognition and an attractive approach for creating novel tools for cell and molecular research. Considerable attention has been placed on redesigning the affinity and specificity of naturally occurring interactions. Several studies have shown that reducing the desolvation costs for binding while preserving shape complimentarity and hydrogen bonding is an effective strategy for improving binding affinities. In favorable cases specificity has been designed by focusing only on interactions with the target protein, while in cases with closely related off-target proteins, it has been necessary to explicitly disfavor unwanted binding partners. The rational design of protein-protein interactions from scratch is still an unsolved problem, but recent developments in flexible backbone design and energy functions hold promise for the future

Evaluation of NASA SPoRT's Pseudo-Geostationary Lightning Mapper Products in the 2011 Spring Program

NASA's Short-term Prediction Research and Transition (SPoRT) program is a contributing partner with the GOES-R Proving Ground (PG) preparing forecasters to understand and utilize the unique products that will be available in the GOES-R era. This presentation emphasizes SPoRT s actions to prepare the end user community for the Geostationary Lightning Mapper (GLM). This preparation is a collaborative effort with SPoRT's National Weather Service partners, the National Severe Storms Laboratory (NSSL), and the Hazardous Weather Testbed s Spring Program. SPoRT continues to use its effective paradigm of matching capabilities to forecast problems through collaborations with our end users and working with the developers at NSSL to create effective evaluations and visualizations. Furthermore, SPoRT continues to develop software plug-ins so that these products will be available to forecasters in their own decision support system, AWIPS and eventually AWIPS II. In 2009, the SPoRT program developed the original pseudo geostationary lightning mapper (PGLM) flash extent product to demonstrate what forecasters may see with GLM. The PGLM replaced the previous GLM product and serves as a stepping-stone until the AWG s official GLM proxy is ready. The PGLM algorithm is simple and can be applied to any ground-based total lightning network. For 2011, the PGLM used observations from four ground-based networks (North Alabama, Kennedy Space Center, Oklahoma, and Washington D.C.). While the PGLM is not a true proxy product, it is intended as a tool to train forecasters about total lightning as well as foster discussions on product visualizations and incorporating GLM-resolution data into forecast operations. The PGLM has been used in 2010 and 2011 and is likely to remain the primary lightning training tool for the GOES-R program for the near future. This presentation will emphasize the feedback received during the 2011 Spring Program. This will discuss several topics. Based on feedback from the 2010 Spring Program, SPoRT created two variant PGLM products, which NSSL produced locally and provided in real-time within AWIPS for 2011. The first is the flash initiation density (FID) product, which creates a gridded display showing the number of flashes that originated in each 8 8 km grid box. The second product is the maximum flash density (MFD). This shows the highest PGLM value for each grid point over a specific period of time, ranging from 30 to 120 minutes. In addition to the evaluation of these two new products, the evaluation of the PGLM itself will be covered. The presentation will conclude with forecaster feedback for additional improvements requested for future evaluations, such as within the 2012 Spring Program