Reasoning about effectful programs and evaluation order

Program transformations have various applications, such as in compiler optimizations. These transformations are often effect-dependent: replacing one program with another relies on some restriction on the side-effects of subprograms. For example, we cannot eliminate a dead computation that raises an exception, or a duplicated computation that prints to the screen. Effect-dependent program transformations can be described formally using effect systems, which annotate types with information about the side-effects of expressions. In this thesis, we extend previous work on effect systems and correctness of effect-dependent transformations in two related directions. First, we consider evaluation order. Effect systems for call-by-value languages are well-known, but are not sound for other evaluation orders. We describe sound and precise effect systems for various evaluation orders, including call-by-name. We also describe an effect system for Levy's call-by-push-value, and show that this subsumes those for call-by-value and call-by-name. This naturally leads us to consider effect-dependent transformations that replace one evaluation order with another. We show how to use the call-by-push-value effect system to prove the correctness of transformations that replace call-by-value with call-by-name, using an argument based on logical relations. Finally, we extend call-by-push-value to additionally capture call-by-need. We use our extension to show a classic example of a relationship between evaluation orders: if the side-effects are restricted to (at most) nontermination, then call-by-name is equivalent to call-by-need. The second direction we consider is non-invertible transformations. A program transformation is non-invertible if only one direction is correct. Such transformations arise, for example, when considering undefined behaviour, nondeterminism, or concurrency. We present a general framework for verifying noninvertible effect-dependent transformations, based on our effect system for call-by-push-value. The framework includes a non-symmetric notion of correctness for effect-dependent transformations, and a denotational semantics based on order-enriched category theory that can be used to prove correctness

Abstract Clones for Abstract Syntax

We give a formal treatment of simple type theories, such as the simply-typed ?-calculus, using the framework of abstract clones. Abstract clones traditionally describe first-order structures, but by equipping them with additional algebraic structure, one can further axiomatize second-order, variable-binding operators. This provides a syntax-independent representation of simple type theories. We describe multisorted second-order presentations, such as the presentation of the simply-typed ?-calculus, and their clone-theoretic algebras; free algebras on clones abstractly describe the syntax of simple type theories quotiented by equations such as ?- and ?-equality. We give a construction of free algebras and derive a corresponding induction principle, which facilitates syntax-independent proofs of properties such as adequacy and normalization for simple type theories. Working only with clones avoids some of the complexities inherent in presheaf-based frameworks for abstract syntax

Galois connecting call-by-value and call-by-name

We establish a general framework for reasoning about the relationship between call-by-value and call-by-name. In languages with computational effects, call-by-value and call-by-name executions of programs often have different, but related, observable behaviours. For example, if a program might diverge but otherwise has no effects, then whenever it terminates under call-by-value, it terminates with the same result under call-by-name. We propose a technique for stating and proving properties like these. The key ingredient is Levy's call-by-push-value calculus, which we use as a framework for reasoning about evaluation orders. We show that the call-by-value and call-by-name translations of expressions into call-by-push-value have related observable behaviour under certain conditions on computational effects, which we identify. We then use this fact to construct maps between the call-by-value and call-by-name interpretations of types, and identify further properties of effects that imply these maps form a Galois connection. These properties hold for some computational effects (such as divergence), but not others (such as mutable state). This gives rise to a general reasoning principle that relates call-by-value and call-by-name. We apply the reasoning principle to example computational effects including divergence and nondeterminism

Ratcheting Up The Search For Dark Matter.

The last several years have included remarkable advances in two of the primary areas of fundamental particle physics: the search for dark matter and the discovery of the Higgs boson. This dissertation will highlight some contributions made on the forefront of these exciting fields. Although the circumstantial evidence supporting the dark matter hypothesis is now almost undeniably significant, indisputable direct proof is still lacking. As the direct searches for dark matter continue, we can maximize our prospects of discovery by using theoretical techniques complementary to the observational searches to rule out additional, otherwise accessible parameter space. In this dissertation, I report bounds on a wide range of dark matter theories. The models considered here cover the spectrum from the canonical case of self-conjugate dark matter with weak-scale interactions, to electrically charged dark matter, to non-annihilating, non-fermionic dark matter. These bounds are obtained from considerations of astrophysical and cosmological data, including, respectively: diffuse gamma ray photon observations; structure formation considerations, along with an explication of the novel local dark matter structure due to galactic astrophysics; and the existence of old pulsars in dark-matter-rich environments. I also consider the prospects for a model of neutrino dark matter which has been motivated by a wide set of seemingly contradictory experimental results. In addition, I include a study that provides the tools to begin solving the speculative ``inverse'' problem of extracting dark matter properties solely from hypothetical nuclear energy spectra, which we may face if dark matter is discovered with multiple direct detection experiments. In contrast to the null searches for dark matter, we have the example of the recent discovery of the Higgs boson. The Higgs boson is the first fundamental scalar particle ever observed, and precision measurements of the production and decay of the Higgs boson represent a unique entry point to searches for new kinds of physics. Continuing to refine our understanding of the Higgs boson will also allow us to learn about a vast array of possible new physics. This dissertation includes work parameterizing some of the scenarios that are most likely to be discovered with future Higgs data.PhDPhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108744/1/mcdermod_1.pd

Association of lower extremity performance with cardiovascular and all-cause mortality in patients with peripheral artery disease: A systematic review and meta-analysis

Background: Peripheral artery disease (PAD) is associated with impaired mobility and a high rate of mortality. The aim of this systematic review was to investigate whether reduced lower extremity performance was associated with an increased incidence of cardiovascular and all‐cause mortality in people with PAD. Methods and Results: A systematic search of the MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane Library databases was conducted. Studies assessing the association between measures of lower extremity performance and cardiovascular or all‐cause mortality in PAD patients were included. A meta‐analysis was conducted combining data from commonly assessed performance tests. The 10 identified studies assessed lower extremity performance by strength tests, treadmill walking performance, 6‐minute walk, walking velocity, and walking impairment questionnaire (WIQ). A meta‐analysis revealed that shorter maximum walking distance was associated with increased 5‐year cardiovascular (unadjusted RR=2.54, 95% CI 1.86 to 3.47, P<10−5, n=1577, fixed effects) and all‐cause mortality (unadjusted RR=2.23 95% CI 1.85 to 2.69, P<10−5, n=1710, fixed effects). Slower 4‐metre walking velocity, a lower WIQ stair‐climbing score, and poor hip extension, knee flexion, and plantar flexion strength were also associated with increased mortality. No significant associations were found for hip flexion strength, WIQ distance score, or WIQ speed score with mortality. Conclusions: A number of lower extremity performance measures are prognostic markers for mortality in PAD and may be useful clinical tools for identifying patients at higher risk of death. Further studies are needed to determine whether interventions that improve measures of lower extremity performance reduce mortality

Engineered Fibrillar Fibronectin Networks as Three‐Dimensional Tissue Scaffolds

Extracellular matrix (ECM) proteins, and most prominently, fibronectin (Fn), are routinely used in the form of adsorbed pre‐coatings in an attempt to create a cell‐supporting environment in both two‐ and three‐dimensional cell culture systems. However, these protein coatings are typically deposited in a form which is structurally and functionally distinct from the ECM‐constituting fibrillar protein networks naturally deposited by cells. Here, the cell‐free and scalable synthesis of freely suspended and mechanically robust three‐dimensional (3D) networks of fibrillar fibronectin (fFn) supported by tessellated polymer scaffolds is reported. Hydrodynamically induced Fn fibrillogenesis at the three‐phase contact line between air, an Fn solution, and a tessellated scaffold microstructure yields extended protein networks. Importantly, engineered fFn networks promote cell invasion and proliferation, enable in vitro expansion of primary cancer cells, and induce an epithelial‐to‐mesenchymal transition in cancer cells. Engineered fFn networks support the formation of multicellular cancer structures cells from plural effusions of cancer patients. With further work, engineered fFn networks can have a transformative impact on fundamental cell studies, precision medicine, pharmaceutical testing, and pre‐clinical diagnostics.Fibrillar fibronectin (fFn) networks are freely suspended across porous polymer structures without the use of cells. Engineered fFn networks enable in vivo implantation or in vitro expansion of various cell types including patient breast cancer cells that otherwise fail to survive on tissue culture polystyrene.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153115/1/adma201904580_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153115/2/adma201904580.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153115/3/adma201904580-sup-0001-S1.pd

A Domain Theory for Statistical Probabilistic Programming

We give an adequate denotational semantics for languages with recursive higher-order types, continuous probability distributions, and soft constraints. These are expressive languages for building Bayesian models of the kinds used in computational statistics and machine learning. Among them are untyped languages, similar to Church and WebPPL, because our semantics allows recursive mixed-variance datatypes. Our semantics justifies important program equivalences including commutativity. Our new semantic model is based on `quasi-Borel predomains'. These are a mixture of chain-complete partial orders (cpos) and quasi-Borel spaces. Quasi-Borel spaces are a recent model of probability theory that focuses on sets of admissible random elements. Probability is traditionally treated in cpo models using probabilistic powerdomains, but these are not known to be commutative on any class of cpos with higher order functions. By contrast, quasi-Borel predomains do support both a commutative probabilistic powerdomain and higher-order functions. As we show, quasi-Borel predomains form both a model of Fiore's axiomatic domain theory and a model of Kock's synthetic measure theory.</p

Early stressful experiences are associated with reduced neural responses to naturalistic emotional and social content in children

How do children’s experiences relate to their naturalistic emotional and social processing? Because children can struggle with tasks in the scanner, we collected fMRI data while 4-to-11-year-olds watched a short film with positive and negative emotional events, and rich parent-child interactions (n = 70). We captured broad, normative stressful experiences by examining socioeconomic status (SES) and stressful life events, as well as children’s more proximal experiences with their parents. For a sub-sample (n = 30), parenting behaviors were measured during a parent-child interaction, consisting of a picture book, a challenging puzzle, and free play with novel toys. We characterized positive parenting behaviors (e.g., warmth, praise) and negative parenting behaviors (e.g., harsh tone, physical control). We found that higher SES was related to greater activity in medial orbitofrontal cortex during parent-child interaction movie events. Negative parenting behaviors were associated with less activation of the ventral tegmental area and cerebellum during positive emotional events. In a region-of-interest analysis, we found that stressful life events and negative parenting behaviors were associated with less activation of the amygdala during positive emotional events. These exploratory results demonstrate the promise of using movie fMRI to study how early experiences may shape emotional, social, and motivational processes