Relational Parametricity for Computational Effects

According to Strachey, a polymorphic program is parametric if it applies a uniform algorithm independently of the type instantiations at which it is applied. The notion of relational parametricity, introduced by Reynolds, is one possible mathematical formulation of this idea. Relational parametricity provides a powerful tool for establishing data abstraction properties, proving equivalences of datatypes, and establishing equalities of programs. Such properties have been well studied in a pure functional setting. Many programs, however, exhibit computational effects, and are not accounted for by the standard theory of relational parametricity. In this paper, we develop a foundational framework for extending the notion of relational parametricity to programming languages with effects.Comment: 31 pages, appears in Logical Methods in Computer Scienc

Engineering stochasticity in gene expression

Stochastic fluctuations (noise) in gene expression can cause members of otherwise genetically identical populations to display drastically different phenotypes. An understanding of the sources of noise and the strategies cells employ to function reliably despite noise is proving to be increasingly important in describing the behavior of natural organisms and will be essential for the engineering of synthetic biological systems. Here we describe the design of synthetic constructs, termed ribosome competing RNAs (rcRNAs), as a means to rationally perturb noise in cellular gene expression. We find that noise in gene expression increases in a manner proportional to the ability of an rcRNA to compete for the cellular ribosome pool. We then demonstrate that operons significantly buffer noise between coexpressed genes in a natural cellular background and can even reduce the level of rcRNA enhanced noise. These results demonstrate that synthetic genetic constructs can significantly affect the noise profile of a living cell and, importantly, that operons are a facile genetic strategy for buffering against noise

Man versus Machine versus Ribozyme

A microfluidic device has been constructed to carry out the automated, continuous evolution of ribozymes. A comparison with manual efforts reveals that both are capable of far flung forays into sequence space

Self-similar Radiation from Numerical Rosenau-Hyman Compactons

The numerical simulation of compactons, solitary waves with compact support, is characterized by the presence of spurious phenomena, as numerically-induced radiation, which is illustrated here using four numerical methods applied to the Rosenau-Hyman K(p,p) equation. Both forward and backward radiations are emitted from the compacton presenting a self-similar shape which has been illustrated graphically by the proper scaling. A grid refinement study shows that the amplitude of the radiations decreases as the grid size does, confirming its numerical origin. The front velocity and the amplitude of both radiations have been studied as a function of both the compacton and the numerical parameters. The amplitude of the radiations decreases exponentially in time, being characterized by a nearly constant scaling exponent. An ansatz for both the backward and forward radiations corresponding to a self-similar function characterized by the scaling exponent is suggested by the present numerical results.Comment: To be published in Journal of Computational Physic

OreSat: A Student Team-Based Approach to an Inexpensive, Open, and Modular (1-3U) CubeSat Bus

Most educational CubeSat projects have the same dilemma: not enough money to buy capable COTS hardware, and not enough internal experience (even with teams of students) to build reliable, and inexpensive systems in-house. We present a middle road to the “COTS vs DIY” conundrum: the OreSat bus. OreSat is a fully open source 1U – 3U CubeSat system meant to be built, modified, and flown by student teams. It’s specifically designed to be put together by resource-constrained student teams with “gaps” in their interdisciplinary breadth, as most teams have. OreSat has everything you would expect from a CubeSat system: a 1 – 3U structure, multi-band deployable antenna, solar array, battery pack, on-board computer, radio system, star tracker, reaction wheels, magnetorquers, and SDR GPS receiver. OreSat is built around a high density card-cage system with roughly a 40% higher packing density than the commonly used PC/104-plus stack. Each system is a “card” based on inexpensive 2 and 4 layer PCBs that interface to a common backplane that is capable of carrying CAN, Ethernet, RF, and power. As each CubeSat is unique, the backplane is made bespoke for each mission with 30% of backplane connections available for customization. Student teams can take the existing OreSat systems and build them as is, or modify them for their missions. The OreSat bus is scheduled for first flight in late 2021 (OreSat0, a 1U technology demonstrator), and will be fully deployed in late 2022 as the 2U “OreSat” mission, accepted into the 2017 NASA CubeSat Launch Initiative (CSLI)

Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder

OBJECTIVE: To investigate depression frequency, severity, current treatment, and interactions with somatic symptoms among patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this dual-center observational study, we included 71 patients diagnosed with NMOSD according to the International Panel for NMO Diagnosis 2015 criteria. The Beck Depression Inventory (BDI) was classified into severe, moderate, or minimal/no depressive state category. We used the Fatigue Severity Scale to evaluate fatigue. Scores from the Brief Pain Inventory and the PainDETECT Questionnaire were normalized to estimate neuropathic pain. Psychotropic, pain, and immunosuppressant medications were tabulated by established classes. RESULTS: Twenty-eight percent of patients with NMOSD (n = 20) had BDI scores indicative of moderate or severe depression; 48% of patients (n = 34) endorsed significant levels of neuropathic pain. Severity of depression was moderately associated with neuropathic pain (r = 0.341, p < 0.004) but this relationship was confounded by levels of fatigue. Furthermore, only 40% of patients with moderate or severe depressive symptoms received antidepressant medical treatment. Fifty percent of those treated reported persistent moderate to severe depressive symptoms under treatment. CONCLUSIONS: Moderate and severe depression in patients with NMOSD is associated with neuropathic pain and fatigue and is insufficiently treated. These results are consistent across 2 research centers and continents. Future research needs to address how depression can be effectively managed and treated in NMOSD

Haptoglobin genotype predicts development of coronary artery calcification in a prospective cohort of patients with type 1 diabetes

<p>Abstract</p> <p>Background</p> <p>Coronary artery disease has been linked with genotypes for haptoglobin (Hp) which modulates extracorpuscular hemoglobin. We hypothesized that the Hp genotype would predict progression of coronary artery calcification (CAC), a marker of subclinical atherosclerosis.</p> <p>Methods</p> <p>CAC was measured three times in six years among 436 subjects with type 1 diabetes and 526 control subjects participating in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Hp typing was performed on plasma samples by polyacrylamide gel electrophoresis.</p> <p>Results</p> <p>The Hp 2-2 genotype predicted development of significant CAC only in subjects with diabetes who were free of CAC at baseline (OR: 1.95, 95% CI: 1.07-3.56, p = 0.03), compared to those without the Hp 2-2 genotype, controlling for age, sex, blood pressure and HDL-cholesterol. Hp 2 appeared to have an allele-dose effect on development of CAC. Hp genotype did not predict CAC progression in individuals without diabetes.</p> <p>Conclusions</p> <p>Hp genotype may aid prediction of accelerated coronary atherosclerosis in subjects with type 1 diabetes.</p

Violence in the lives of incarcerated aboriginal mothers in Western Australia

Drawing on in-depth interviews with incarcerated Aboriginal and Torres Strait Islander mothers in Western Australia, we report on the women’s use of violence in their relationships with others. Results reinforce that Aboriginal women are overwhelmingly victims of violence; however, many women report also using violence, primarily as a strategy to deal with their own high levels of victimization. The “normalization” of violence in their lives and communities places them at high risk of arrest and incarceration. This is compounded by a widespread distrust of the criminal justice system and associated agencies, and a lack of options for community support.The original study on which this article is based, the Social and Cultural Resilience and Emotional Wellbeing of Aboriginal Mothers in Prison, was supported by the National Health and Medical Research Council of Australia (Project Grant ID: 630653). The analysis and drafting of this article was further supported through the NHMRC-funded Indigenous Offender Health Research Capacity Building Grant (APP: 533546)