Logical Step-Indexed Logical Relations

Appel and McAllester's "step-indexed" logical relations have proven to be a simple and effective technique for reasoning about programs in languages with semantically interesting types, such as general recursive types and general reference types. However, proofs using step-indexed models typically involve tedious, error-prone, and proof-obscuring step-index arithmetic, so it is important to develop clean, high-level, equational proof principles that avoid mention of step indices. In this paper, we show how to reason about binary step-indexed logical relations in an abstract and elegant way. Specifically, we define a logic LSLR, which is inspired by Plotkin and Abadi's logic for parametricity, but also supports recursively defined relations by means of the modal "later" operator from Appel, Melli\`es, Richards, and Vouillon's "very modal model" paper. We encode in LSLR a logical relation for reasoning relationally about programs in call-by-value System F extended with general recursive types. Using this logical relation, we derive a set of useful rules with which we can prove contextual equivalence and approximation results without counting steps

First trimester elevation in circulating endothelin-1 and arterial stiffness are predictive of late pregnancy preeclampsia

Preeclampsia (PE) is characterized by late pregnancy hypertension and proteinuria. PE causes significant morbidity for the maternal-fetal unit. Circulating endothelin-1 (ET-1), a potent vasoconstrictor, is elevated at the time of diagnosis of human PE. In addition, women with PE demonstrate arterial stiffness as early as the end of the first trimester. However, it is unknown if arterial stiffness is associated with a first trimester elevation in ET-1 and post-delivery placental ET-1. We hypothesized that 1) first trimester plasma ET-1 is elevated and is associated with arterial stiffness in women who develop PE; 2) first trimester ET-1 is predictive of PE; and 3) placental ET-1 is increased in PE. To address these questions, we performed a nested case-control study in women at risk for P

Analytical characterization of bioactive N-benzyl-substituted phenethylamines and 5-methoxytryptamines

RATIONALE: Substances based on the N-(2-methoxybenzyl)phenethylamine template (‘NBOMe’ derivatives) play an important role in medicinal research but some of these derivatives have also appeared as ‘research chemicals’ for recreational use which attracted attention worldwide. A major challenge associated with newly emerging substances includes the lack of analytical data and the ability to correctly identify positional isomers. METHODS: Six N-benzylphenethylamines based on the 2,5-dimethoxy-4-iodophenethylamine structure (‘25I’) and twelve substituted N-benzyl-5-methoxytryptamines (‘5MT’) have been prepared and extensively characterized. Techniques used for characterization were gas chromatography ion trap mass spectrometry in electron and chemical ionization mode, liquid chromatography diode array detection (DAD), infrared spectroscopy, electrospray high mass accuracy quadrupole time-of-flight tandem mass spectrometry, and triple quadrupole tandem mass spectrometry. RESULTS: The characterization of eighteen ‘NBOMe’ analogs provided a comprehensive collection of chromatographic and spectral data. Four groups of three positional isomers, i.e. 25I-NB2OMe, 25I-NB3OMe, 25I-NB4OMe, 25I-NB2B, 25INB3B, 25I-NB4B and their 5-methoxytryptamine counterparts, were included and assessed for ability to differentiate between them. Six meta-substituted N-benzyl derivatives of 5-methoxytryptamine (CF3, F, CH3, Cl, I, SCH3) were also studied. CONCLUSIONS: The implementation of mass spectral techniques was helpful for the differentiation between isomers, for example, when considering the difference in a number of ion ratios. This was considered beneficial in cases where chromatographic separation was only partially achieved under liquid chromatography (LC) conditions. The use of LC/DAD analysis was also found to be valuable for this particular purpose, which confirmed the integrative value of complementary techniques for areas related to forensic toxicology

Experimental and Theoretical Investigation into the Effect of the Electron Velocity Distribution on Chaotic Oscillations in an Electron Beam under Virtual Cathode Formation Conditions

The effect of the electron transverse and longitudinal velocity spread at the entrance to the interaction space on wide-band chaotic oscillations in intense multiple-velocity beams is studied theoretically and numerically under the conditions of formation of a virtual cathode. It is found that an increase in the electron velocity spread causes chaotization of virtual cathode oscillations. An insight into physical processes taking place in a virtual cathode multiple velocity beam is gained by numerical simulation. The chaotization of the oscillations is shown to be associated with additional electron structures, which were separated out by constructing charged particle distribution functions.Comment: 9 pages, 8 figure

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

A measurement of the W boson mass using large rapidity electrons

We present a measurement of the W boson mass using data collected by the D0 experiment at the Fermilab Tevatron during 1994--1995. We identify W bosons by their decays to e-nu final states where the electron is detected in a forward calorimeter. We extract the W boson mass, Mw, by fitting the transverse mass and transverse electron and neutrino momentum spectra from a sample of 11,089 W -> e nu decay candidates. We use a sample of 1,687 dielectron events, mostly due to Z -> ee decays, to constrain our model of the detector response. Using the forward calorimeter data, we measure Mw = 80.691 +- 0.227 GeV. Combining the forward calorimeter measurements with our previously published central calorimeter results, we obtain Mw = 80.482 +- 0.091 GeV

Science Gateways and AI/ML: How Can Gateway Concepts and Solutions Meet the Needs in Data Science?

Science gateways are a crucial component of critical infrastructure as they provide the means for users to focus on their topics and methods instead of the technical details of the infrastructure. They are defined as end-to-end solutions for accessing data, software, computing services, sensors, and equipment specific to the needs of a science or engineering discipline and their goal is to hide the complexity of the underlying infrastructure. Science gateways are often called Virtual Research Environments in Europe and Virtual Labs in Australasia; we consider these two terms to be synonymous with science gateways. Over the past decade, artificial intelligence (AI) and machine learning (ML) have found applications in many different fields in private industry, and private industry has reaped the benefits. Likewise, in the academic realm, large-scale data science applications have also learned to apply public high-performance computing resources to make use of this technology. However, academic and research science gateways have yet to fully adopt the tools of AI. There is an opportunity in the gateways space, both to increase the visibility and accessibility to AI/ML applications and to enable researchers and developers to advance the field of science gateway cyberinfrastructure itself. Harnessing AI/ML is recognized as a high priority by the science gateway community. It is, therefore, critical for the next generation of science gateways to adapt to support the AI/ML that is already transforming many scientific fields. The goal is to increase collaborations between the two fields and to ensure that gateway services are used and are valuable to the AI/ML community. This chapter presents state-of-the-art examples and areas of opportunity for the science gateways community to pursue in relation to AI/ML and some vision of where these new capabilities might impact science gateways and support scientific research

Comparison of outpatient health care utilization among returning women and men Veterans from Afghanistan and Iraq

<p>Abstract</p> <p>Background</p> <p>The number of women serving in the United States military increased during Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF), leading to a subsequent surge in new women Veterans seeking health care services from the Veterans Administration (VA). The objective of this study was to examine gender differences among OEF/OIF Veterans in utilization of VA outpatient health care services.</p> <p>Methods</p> <p>Our retrospective cohort consisted of 1,620 OEF/OIF Veterans (240 women and 1380 men) who enrolled for outpatient healthcare at a single VA facility. We collected demographic data and information on military service and VA utilization from VA electronic medical records. To assess gender differences we used two models: use versus nonuse of services (logistic regression) and intensity of use among users (negative binomial regression).</p> <p>Results</p> <p>In our sample, women were more likely to be younger, single, and non-white than men. Women were more likely to utilize outpatient care services (odds ratio [OR] = 1.47, 95% confidence interval [CI]:1.09, 1.98), but once care was initiated, frequency of visits over time (intensity) did not differ by gender (incident rate ratio [IRR] = 1.07; 95% CI: 0.90, 1.27).</p> <p>Conclusion</p> <p>Recently discharged OEF/OIF women Veterans were more likely to seek VA health care than men Veterans. But the intensity of use was similar between women and men VA care users. As more women use VA health care, prospective studies exploring gender differences in types of services utilized, health outcomes, and factors associated with satisfaction will be required.</p

In Vivo Delta Opioid Receptor Internalization Controls Behavioral Effects of Agonists

GPCRs regulate a remarkable diversity of biological functions, and are thus often targeted for drug therapies. Stimulation of a GPCR by an extracellular ligand triggers receptor signaling via G proteins, and this process is highly regulated. Receptor activation is typically accompanied by desensitization of receptor signaling, a complex feedback regulatory process of which receptor internalization is postulated as a key event. The in vivo significance of GPCR internalization is poorly understood. In fact, the majority of studies have been performed in transfected cell systems, which do not adequately model physiological environments and the complexity of integrated responses observed in the whole animal.In this study, we used knock-in mice expressing functional fluorescent delta opioid receptors (DOR-eGFP) in place of the native receptor to correlate receptor localization in neurons with behavioral responses. We analyzed the pain-relieving effects of two delta receptor agonists with similar signaling potencies and efficacies, but distinct internalizing properties. An initial treatment with the high (SNC80) or low (AR-M100390) internalizing agonist equally reduced CFA-induced inflammatory pain. However, subsequent drug treatment produced highly distinct responses. Animals initially treated with SNC80 showed no analgesic response to a second dose of either delta receptor agonist. Concomitant receptor internalization and G-protein uncoupling were observed throughout the nervous system. This loss of function was temporary, since full DOR-eGFP receptor responses were restored 24 hours after SNC80 administration. In contrast, treatment with AR-M100390 resulted in retained analgesic response to a subsequent agonist injection, and ex vivo analysis showed that DOR-eGFP receptor remained G protein-coupled on the cell surface. Finally SNC80 but not AR-M100390 produced DOR-eGFP phosphorylation, suggesting that the two agonists produce distinct active receptor conformations in vivo which likely lead to differential receptor trafficking.Together our data show that delta agonists retain full analgesic efficacy when receptors remain on the cell surface. In contrast, delta agonist-induced analgesia is abolished following receptor internalization, and complete behavioral desensitization is observed. Overall these results establish that, in the context of pain control, receptor localization fully controls receptor function in vivo. This finding has both fundamental and therapeutic implications for slow-recycling GPCRs