Advances in Dynamic Modeling and Computation for Count Data

A class of multi-process models is developed for collections of time indexed count data. Autocorrelation in counts is achieved with dynamic models for the natural parameter of the binomial distribution. In addition to modeling binomial time series, the framework includes dynamic models for multinomial and Poisson time series. Markov chain Monte Carlo (MCMC) and Po ́lya-Gamma data augmentation (Polson et al., 2013) are critical for fitting multi-process models of counts. To facilitate computation when the counts are high, a Gaussian approximation to the P ́olya- Gamma random variable is developed.

Three applied analyses are presented to explore the utility and versatility of the framework. The first analysis develops a model for complex dynamic behavior of themes in collections of text documents. Documents are modeled as a “bag of words”, and the multinomial distribution is used to characterize uncertainty in the vocabulary terms appearing in each document. State-space models for the natural parameters of the multinomial distribution induce autocorrelation in themes and their proportional representation in the corpus over time.

The second analysis develops a dynamic mixed membership model for Poisson counts. The model is applied to a collection of time series which record neuron level firing patterns in rhesus monkeys. The monkey is exposed to two sounds simultaneously, and Gaussian processes are used to smoothly model the time-varying rate at which the neuron’s firing pattern fluctuates between features associated with each sound in isolation.

The third analysis presents a switching dynamic generalized linear model for the time-varying home run totals of professional baseball players. The model endows each player with an age specific latent natural ability class and a performance enhancing drug (PED) use indicator. As players age, they randomly transition through a sequence of ability classes in a manner consistent with traditional aging patterns. When the performance of the player significantly deviates from the expected aging pattern, he is identified as a player whose performance is consistent with PED use.

All three models provide a mechanism for sharing information across related series locally in time. The models are fit with variations on the P ́olya-Gamma Gibbs sampler, MCMC convergence diagnostics are developed, and reproducible inference is emphasized throughout the dissertation.

Fermion bag approach to lattice field theories

We propose a new approach to the fermion sign problem in systems where there is a coupling U such that when it is infinite the fermions are paired into bosons, and there is no fermion permutation sign to worry about. We argue that as U becomes finite, fermions are liberated but are naturally confined to regions which we refer to as fermion bags. The fermion sign problem is then confined to these bags and may be solved using the determinantal trick. In the parameter regime where the fermion bags are small and their typical size does not grow with the system size, construction of Monte Carlo methods that are far more efficient than conventional algorithms should be possible. In the region where the fermion bags grow with system size, the fermion bag approach continues to provide an alternative approach to the problem but may lose its main advantage in terms of efficiency. The fermion bag approach also provides new insights and solutions to sign problems. A natural solution to the "silver blaze problem" also emerges. Using the three-dimensional massless lattice Thirring model as an example, we introduce the fermion bag approach and demonstrate some of these features. We compute the critical exponents at the quantum phase transition and find ν=0.87(2) and η=0.62(2). © 2010 The American Physical Society.

A novel, non-apoptotic role for Scythe/BAT3: a functional switch between the pro- and anti-proliferative roles of p21 during the cell cycle.

BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.

Akrasia and the Aesthetic: Human Agency and the Site of Literature, 1760-1820

This study focuses on a series of foundational stylistic and formal innovations in eighteenth-century and Romantic literature, and argues that they can be cumulatively attributed to the distinct challenges authors faced in representing human action and the will. The study focuses in particular on cases of “acting against better judgment” or “failing to do what one knows one ought to do” – concepts originally theorized as “akrasia” and “weakness of the will” in ancient Greek and Scholastic thought. During the Enlightenment, philosophy increasingly conceives of human minds and bodies like systems and machines, and consequently fails to address such cases except as intractable or incoherent. Yet eighteenth-century and Romantic narratives and poetry consistently engage the paradoxes and ambiguities of action and volition in representations of akrasia. As a result, literature develops representational strategies that distinguish the epistemic capacities of literature as privileged over those of philosophy.

The study begins by centering on narratives of distempered selves from the 1760s. Jean-Jacques Rousseau’s Confessions and Laurence Sterne’s A Sentimental Journey narrate cases of knowingly and weakly acting against better judgment, and in so doing, reveal the limitations of the “philosophy of the passions” that famously informed sentimental literature at the time. These texts find that the interpretive difficulties of action demand a non-systematic and hermeneutic approach to interpreting a self through the genre of narrative. Rousseau’s narrative in particular informs William Godwin’s realist novels of distempered subjects. Departing from his mechanistic philosophy of mind and action, Godwin develops the technique of free indirect discourse in his third novel Fleetwood (1805) as a means of evoking the ironies and self-deceptions in how we talk about willing.

Romantic poetry employs the literary trope of weakness of will primarily through the problem of regretted inaction – a problem which I argue motivates the major poetic innovations of William Wordsworth and John Keats. While Samuel Taylor Coleridge sought to characterize his weakness of will in philosophical writing, Wordsworth turns to poetry with The Prelude (1805), revealing poetry itself to be a self-deceiving and disappointing form of procrastination. More explicitly than Wordsworth, John Keats identifies indolence as the prime symbol and basis of what he calls “negative capability.” In his letters and poems such as “On Seeing the Elgin Marbles” (1817) and “Ode on Indolence” (1819), Keats reveals how the irreducibly contradictory qualities of human agency speak to the particular privilege of “disinterested aesthetics” – a genre fitted for the modern era for its ability to disclose contradictions without seeking to resolve or explain them in terms of component parts.