Cardiac resynchronization therapy (CRT) is an effective treatment for dyssynchronous heart failure. Most patients perform better during clinical tests of cardiac function and may even have their hearts reverse remodel to a more normal state. As many as 30-40% of patients, however, do not respond. A focus of current research is identifying which patients will respond to CRT, though current clinical indications for CRT are based on dyssynchrony and heart failure and not on validated predictors of CRT response. In this thesis, five patient-specific computational models based on non-invasive data were developed and compared with eight previous patient-specific models that were based on more detailed and invasive clinical information to test whether the dyssynchrony metrics from the original study were still predictive in the new group. Model properties such as the volume fraction of negative work (VFNW) and coefficient of variation of work (COVW), that had correlated with patient outcomes in the original cohort, did not correlate with reverse remodeling as measured by reduction in end-systolic volume in the new group. The sensitivity analysis showed that these quantities were sensitive to the parameters of ventricular filling mechanics that could not be included in patient-specific models based on non-invasive data. Non-invasive estimates of filling parameters are available, but their reliability has been questioned. We conclude that it is likely to be necessary to obtain invasive measurements of diastolic pressures for patient-specific models to predict CRT outcomes. However, these measurements are available by cardiac catheterization, which could be justified for CRT patients.

An n- armed bandit task was used to investigate the trade-off between exploratory (choosing lesser-known options) and exploitive (choosing options with the greatest known probability of reinforcement) human choice in a trial-and-error learning problem. A different probability of reinforcement was assigned to each of eight response options using random-ratios (RRs), and participants chose by clicking buttons in a circular display on a computer screen using a computer mouse.  To differentially increase exploration, relative frequency thresholds were randomly assigned to each participant and acted as task constraints limiting the proportion of total responses that could be attributed to any response option. The potential benefit of increased exploration in non-stationary environments was investigated by changing payoff probabilities so that the leanest options became the richest or the richest options became the leanest. On the average, forcing participants to explore at moderate to high levels always resulted in their earning less reinforcement, even when the payoffs changed.  This outcome may be due to humans’ natural level of exploration in our task being sufficiently high to create sensitivity to environmental dynamics.

Enzymes are capable of exquisite selectivity in catalysis chemical reactions because of a well-evolved mechanism that binds substrates in internal active sites based on size and shape complementarity. The cavities of these enzymes are decorated with organic or inorganic groups which can promote reactivity once the substrate is non-covalently bound. Synthetic molecular hosts to date have been able to bind to substrates in a similar, biomimetic fashion, but functionalized molecular hosts are still virtually unknown. One convenient way to prepare molecular hosts is by the self-assembly of organic coordinating ligands with suitable metal salts. The reversible dative bonds holding these cage structures together allow incorrect products to break apart and reform, favoring creation of the most thermodynamically stable product. This leads to discrete, solution phase cages that can function as cavity-containing hosts. Some of these hosts have shown efficacy as catalysts for pericyclic reactions due to favorable transition states of the bound substrates. These cages, however, fail to orient reactive functional groups into their interiors. Truly biomimetic cages will require modifying traditional self-assembled targets to incorporate these reactive functionalities. This work explores the self-assembly of metal-organic cages displaying covalent modifications on their interior. Incorporation of unreactive and poorly reactive groups was found to have a significant impact on the outcome of the self-assembly process. Cages with endohedral alcoholic functionality were found to have different binding properties than unfunctionalized analogs. Cages with introverted alcohol groups were also exploited for their ability to self-catalyze reactions on the interior of the hosts. The metal vertices themselves could also be used as functional groups, and showed the ability to sense neutral analytes in hybrid dative/hydrogen bonded self-assemblies.