Counterfactual Double Lives

Expressions typically thought to be rigid designators can refer to distinct individuals in the consequents of counterfactuals. This occurs in counteridenticals, such as “If I were you, I would arrest me”, as well as more ordinary counterfactuals with clearly possible antecedents, like “If I were a police officer, I would arrest me”. I argue that in response we should drop rigidity and deal with de re modal predication using something more flexible, such as counterpart theory

MODELING AND EXPERIMENTAL INVESTIGATIONS OF THE SHOCK RESPONSE OF VISCOELASTIC FOAMS

This thesis presents a new constitutive model for closed-cell foams tailored for compressive shock loads and an experimental investigation of two commercial foam products. The new model requires just two characterization experiments to find material parameters, making it far more convenient than other approaches. A specific form of the hyperelastic free energy function is developed that permits an extension of a three-phase composite theory to finite strain hyperelasticity providing the following advantages: 1) identification of the hyperelastic free energy contributions associated with the gas and material phases, 2) elimination of deviatoric experiments for parameter determination, and 3) proper behavior at the densification limit. A viscoelastic model of the matrix shear modulus is used to introduce rate effects and plasticity. A time-incremental formulation of the constitutive model is developed and implemented using a finite element approach. Model results are compared with data obtained in high strain-rate experiments

Conceptual Limitations, Puzzlement, and Epistemic Dilemmas

Conceptual limitations restrict our epistemic options. One cannot believe, disbelieve, or doubt what one cannot grasp. I show how such restrictions could lead to epistemic dilemmas: situations in which each of one’s options violates some epistemic requirement. To help the dilemmist distinguish their view of these cases from alternative non-dilemmic analyses, I propose to treat puzzlement as a kind of epistemic residue, appropriate only when one has violated an epistemic requirement. As moral dilemmists have appealed to unavoidable guilt as a sign of a moral dilemma, so too can the epistemic dilemmist appeal to unavoidable puzzlement as a sign of an epistemic dilemma. I conclude by considering why, on the dilemmist’s view, it sometimes makes sense for inquirers to seek out puzzlement

Offsetting Harm

It is typically wrong to act in a way that foreseeably makes some impending harm worse. Sometimes it is permissible to do so, however, if one also offsets the harm increasing action by doing something that decreases the badness of the same harm by at least as much. This chapter argues that the standard deontological constraint against doing harm is not compatible with the permissibility of harm increases that have been offset. Offsetting neither prevents one's other actions from doing harm nor ensures that the harm those actions do is made permissible by any of the constraint's familiar provisos. To make sense of offsetting, the old constraint against doing harm should be replaced with a new constraint against making unoffset harm increases. The chapter discusses how to formulate the new constraint so that it can handle both the offsetting cases that the old constraint gets wrong as as well as the non-offsetting cases that the old constraint gets right. Adopting this constraint against unoffset harm increases may have important implications both for theoretical questions about the sources of deontological constraints as well as for practical questions, such as whether buying carbon offsets can make emitting carbon dioxide permissible

A Fitting Definition of Epistemic Emotions

Philosophers and psychologists sometimes categorize emotions like surprise and curiosity as specifically epistemic. Is there some reasonably unified and interesting class of emotions here? If so, what unifies it? This paper proposes and defends an evaluative account of epistemic emotions: what it is to be an epistemic emotion is to have fittingness conditions that distinctively involve some epistemic evaluation. We argue that this view has significant advantages over alternative proposals and is a promising way to identify a limited and interesting class of emotions

HiTRACE: High-throughput robust analysis for capillary electrophoresis

Motivation: Capillary electrophoresis (CE) of nucleic acids is a workhorse technology underlying high-throughput genome analysis and large-scale chemical mapping for nucleic acid structural inference. Despite the wide availability of CE-based instruments, there remain challenges in leveraging their full power for quantitative analysis of RNA and DNA structure, thermodynamics, and kinetics. In particular, the slow rate and poor automation of available analysis tools have bottlenecked a new generation of studies involving hundreds of CE profiles per experiment. Results: We propose a computational method called high-throughput robust analysis for capillary electrophoresis (HiTRACE) to automate the key tasks in large-scale nucleic acid CE analysis, including the profile alignment that has heretofore been a rate-limiting step in the highest throughput experiments. We illustrate the application of HiTRACE on thirteen data sets representing 4 different RNAs, three chemical modification strategies, and up to 480 single mutant variants; the largest data sets each include 87,360 bands. By applying a series of robust dynamic programming algorithms, HiTRACE outperforms prior tools in terms of alignment and fitting quality, as assessed by measures including the correlation between quantified band intensities between replicate data sets. Furthermore, while the smallest of these data sets required 7 to 10 hours of manual intervention using prior approaches, HiTRACE quantitation of even the largest data sets herein was achieved in 3 to 12 minutes. The HiTRACE method therefore resolves a critical barrier to the efficient and accurate analysis of nucleic acid structure in experiments involving tens of thousands of electrophoretic bands.Comment: Revised to include Supplement. Availability: HiTRACE is freely available for download at http://hitrace.stanford.ed

Accurate SHAPE-directed RNA structure determination

Almost all RNAs can fold to form extensive base-paired secondary structures. Many of these structures then modulate numerous fundamental elements of gene expression. Deducing these structure–function relationships requires that it be possible to predict RNA secondary structures accurately. However, RNA secondary structure prediction for large RNAs, such that a single predicted structure for a single sequence reliably represents the correct structure, has remained an unsolved problem. Here, we demonstrate that quantitative, nucleotide-resolution information from a SHAPE experiment can be interpreted as a pseudo-free energy change term and used to determine RNA secondary structure with high accuracy. Free energy minimization, by using SHAPE pseudo-free energies, in conjunction with nearest neighbor parameters, predicts the secondary structure of deproteinized Escherichia coli 16S rRNA (>1,300 nt) and a set of smaller RNAs (75–155 nt) with accuracies of up to 96–100%, which are comparable to the best accuracies achievable by comparative sequence analysis