Optimal integration of auditory and vibrotactile information for judgments of temporal order

Recent research that assessed spatial judgments about multisensory stimuli suggests that humans integrate multisensory inputs in a statistically optimal manner by weighting each input by its normalized reciprocal variance. Is integration similarly optimal When humans judge the temporal properties of bimodal stimuli? Twenty-four participants performed temporal order judgments (TOJs,) about 2 spatially separated stimuli. Stimuli were auditory, vibrotactile, or both. The temporal profiles of vibrotactile stimuli were manipulated to produce 3 levels of precision for TOJs. In bimodal conditions, the asynchrony between the 2 unimodal stimuli that comprised it bimodal Stimulus was manipulated to determine the weight given to touch. Bimodal performance on 2 measures-judgment uncertainty and tactile weight-was predicted With unimodal data. A model relying exclusively on audition wits rejected on the basis of both measures. A second model that selected the best input on each trial did not predict the reduced judgment uncertainty observed in bimodal trials. Only the optimal Maximum-likelihood-estimation model predicted both judgment uncertainties and weights the model's validity is extended to TOJs. Alternatives for modeling the process of event sequencing based on integrated multisensory inputs are discussed

Spatially and Intertemporally Efficient Waste Management: The Costs of Interstate Flow Control

We examine the intertemporal allocation of the solid waste of cities within the United States to spatially distributed landfills and incinerators, taking into account that capacity at existing and potential landfills is scarce. Amendments have been proposed to restrict waste flows between states by means of quotas and surcharges. We assess the aggregate surplus loss (and its regional distribution) resulting from proposed policies. In addition, we find that limitations on the size of shipments to any one state can have the perverse effect of substantially increasing interstate waste shipments as states export smaller volumes to more destinations.Solid Waste, Efficiency, Hotelling

Molecular simulation of protein adhesion for rational design of antimicrobial surfaces

This thesis employs atomistic level modelling to investigate behaviour of surfaces protected through functionalisation with short organic ligands, and their interaction with protein contaminants. A detailed description of the motivation for this project, a detailed literature review on the biofouling process, strategies to prevent biofouling and anti-fouling theory are presented in Chapter 1. Classical Molecular Dynamics (MD) techniques are employed to describe the behaviour of our functionalised surfaces in aqueous environments, and the physical interactions with our protein contaminant, EAS hydrophobin. A detailed description of these computational techniques is included in Chapter 2. In Chapter 3, we outline the challenges and limitations of molecular modelling techniques, followed by a detailed background in the development and validation of silica and polyester substrates that have been used in this study. We have also included a detailed description of the computational surface models and surface functionalisation process. In order to tailor surfaces for specific applications, the underlying molecular mechanism that enables a functionalised surface to change properties in response to an external trigger must be understood. In Chapter 4 we investigate de-swelling and swelling of some of the most commonly used responsive materials, poly(ethylene glycol) (PEG) functionalised silica and polymer surfaces, as a function of hydration and temperature. We also investigate the difference between the hard (silica) and soft (polyester) substrates, and PEG grafting density on responsive behaviour. We show that enhancement of the surface hardness must be considered when designing responsive surfaces for solution based applications, such as antimicrobial coatings for interchangeable wet/dry environments and biomedicine. In Chapter 5, we compare the hydration and chain dynamics of PEG and poly(2-oxazoline) (POX) modified silica surfaces as a function of heterogeneity. We assess how chemistry and surface density of commonly used anti-fouling surface ligands affect the interfacial properties relevant to biofouling. We show how existing theories that attempt to explain underlying molecular mechanisms of biofilm formation and its attenuation are not consistent with experiments, and detail findings that can be exploited in the rational design of biofouling resistant surfaces for industrial and biomedical applications. To better understand our protein contaminant, EAS hydrophobin, we study the initial stages of monomeric EAS hydrophobin’s spontaneous adsorption on fully hydroxylated silica. Presented in Chapter 6, a series of MD simulations are undertaken with EAS in solvent only, and also positioned above the silica surface, enabling us to gain a better understanding of EAS’ behaviour in solvent phase, and at interfaces. This allows us to explore the anti-fouling efficacy of PEG and POX surface coatings. Combining the detailed knowledge of our surfaces, and the protein, in Chapter 7 we look to elucidate whether entropic barriers associated with surface mobility or those from interfacial water have greater contributions to anti-fouling efficacy. To do this, we simulate the initial stages of the spontaneous adsorption of monomeric EAS hydrophobin on PEG and POX functionalised silica surfaces. From the knowledge gained, we have developed several updated design principles and an updated understanding of anti-fouling surfaces, which we summarise in Chapter 8. Several ideas for continuation of research in anti-fouling surfaces is then presented in the Future Work section

Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophages.

Genome-wide investigations of host-pathogen interactions are often limited by analyses of mixed populations of infected and uninfected cells, which lower sensitivity and accuracy. To overcome these obstacles and identify key mechanisms by which Zika virus (ZIKV) manipulates host responses, we developed a system that enables simultaneous characterization of genome-wide transcriptional and epigenetic changes in ZIKV-infected and neighboring uninfected primary human macrophages. We demonstrate that transcriptional responses in ZIKV-infected macrophages differed radically from those in uninfected neighbors and that studying the cell population as a whole produces misleading results. Notably, the uninfected population of macrophages exhibits the most rapid and extensive changes in gene expression, related to type I IFN signaling. In contrast, infected macrophages exhibit a delayed and attenuated transcriptional response distinguished by preferential expression of IFNB1 at late time points. Biochemical and genomic studies of infected macrophages indicate that ZIKV infection causes both a targeted defect in the type I IFN response due to degradation of STAT2 and reduces RNA polymerase II protein levels and DNA occupancy, particularly at genes required for macrophage identity. Simultaneous evaluation of transcriptomic and epigenetic features of infected and uninfected macrophages thereby reveals the coincident evolution of dominant proviral or antiviral mechanisms, respectively, that determine the outcome of ZIKV exposure

Detecting the direction of a signal on high-dimensional spheres: Non-null and Le Cam optimality results

We consider one of the most important problems in directional statistics, namely the problem of testing the null hypothesis that the spike direction $\theta$ of a Fisher-von Mises-Langevin distribution on the $p$-dimensional unit hypersphere is equal to a given direction $\theta_0$. After a reduction through invariance arguments, we derive local asymptotic normality (LAN) results in a general high-dimensional framework where the dimension $p_n$ goes to infinity at an arbitrary rate with the sample size $n$, and where the concentration $\kappa_n$ behaves in a completely free way with $n$, which offers a spectrum of problems ranging from arbitrarily easy to arbitrarily challenging ones. We identify various asymptotic regimes, depending on the convergence/divergence properties of $(\kappa_n)$, that yield different contiguity rates and different limiting experiments. In each regime, we derive Le Cam optimal tests under specified $\kappa_n$ and we compute, from the Le Cam third lemma, asymptotic powers of the classical Watson test under contiguous alternatives. We further establish LAN results with respect to both spike direction and concentration, which allows us to discuss optimality also under unspecified $\kappa_n$. To investigate the non-null behavior of the Watson test outside the parametric framework above, we derive its local asymptotic powers through martingale CLTs in the broader, semiparametric, model of rotationally symmetric distributions. A Monte Carlo study shows that the finite-sample behaviors of the various tests remarkably agree with our asymptotic results.Comment: 47 pages, 4 figure

Empirical corrections to the Amber RNA force field with Target Metadynamics

The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the \u3b1 and \u3b6 backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement