International Economic Agreements and the Constitution

International agreements, such as the General Agreement on Tariffs and Trade (GATT) and the North American Free Trade Agreement (NAFTA), generally aim to facilitate the free flow of goods and services among nations.1 The U.S. Supreme Court has developed a jurisprudence similarly aiming to facilitate the free flow of goods and services among the several states. That jurisprudence has developed from litigation challenging the constitutionality of state actions on the basis of the Commerce and Supremacy Clauses of the Constitution (art. I, § 8, cl. 3, and art. VI, cl. 2). In some subject areas, Commerce Clause decisions closely align with international agreements. In other areas, either or both fall short of achieving economic integration.

Dive Behavior of Eastern Chukchi Beluga Whales (Delphinapterus leucas), 1998–2008

We provide an exploratory description of the dive behavior of 23 beluga whales of the eastern Chukchi Sea stock, tagged with satellite-linked time and depth recorders at Point Lay, Alaska, between 1998 and 2007. Because of differences in how transmitters were parameterized, we analyzed data from tags deployed from 1998 to 2002 (n = 20 tags) and data from tags deployed in 2007 (n = 3 tags) separately. Using cluster analysis, we found three basic dive types in the 1998–2002 dataset. “Shallow” diving behavior was characterized by dives mostly 50 m in depth. “Intermediate” diving behavior was characterized by having one mode near the surface and a second mode near 250 m. “Deep” diving behavior was characterized by having one mode near the surface and a second mode more than 400 m from the surface. The average number of dives per hour ranged from 5.1 (SD = 2.1) to 9.8 (SD = 2.9) across dive types, with the fewest dives per hour in the deep diving category. In general, duration of dives ranged from 1 to 18 minutes; however, dives up to 21 minutes occurred in the deepest diving category. We found little evidence that dive behavior of the belugas in our sample varied by sex or age. In general, belugas dove more deeply in the eastern Beaufort Sea than in the western Beaufort or Chukchi Seas. The depths to which belugas most commonly dive in Barrow Canyon and along the Beaufort shelf break (200–300 m) correspond to the boundary where colder Pacific water overlies warmer Atlantic water, which is probably where Arctic cod (Boreogadus saida) are most dense. Diving depths within the Arctic Basin suggest that belugas are foraging mostly within the warm layer of Atlantic Water (~200–1000 m).Nous dressons une description exploratoire du comportement de plongée de 23 bélugas du cheptel de l’est de la mer des Tchouktches dotés de marqueurs d’enregistreurs satellitaires de profondeur temporelle à Point Lay, en Alaska, entre 1998 et 2007. En raison des différences de paramétrage des transmetteurs, nous avons analysé séparément les données de marqueurs déployés de 1998 à 2002 (n = 20 marqueurs) et les données de marqueurs déployés en 2007 (n = 3 marqueurs). Grâce à une analyse par grappes, nous avons trouvé trois types de plongée fondamentaux dans l’ensemble des données de 1998 à 2002. Le comportement de plongée « en eau peu profonde » était principalement caractérisé par des plongées de 50 m de profondeur. Le comportement de plongée « intermédiaire » était caractérisé par un mode de plongée près de la surface et un autre mode à près de 250 m. Le comportement de plongée « en profondeur » était caractérisé par un mode de plongée près de la surface et un deuxième mode à plus de 400 m de la surface. Le nombre moyen de plongées à l’heure variait de 5,1 (écart-type = 2,1) à 9,8 (écart-type = 2,9) pour ce qui est de tous les types de plongée, la catégorie des plongées en profondeur ayant enregistré le moins grand nombre de plongées. En général, la durée des plongées durait de 1 à 18 minutes, mais cela dit, certaines des plongées en profondeur ont duré jusqu’à 21 minutes. Nous avons trouvé peu d’indices portant à croire que le comportement de plongée des bélugas de notre échantillon variait en fonction du sexe ou de l’âge. De manière générale, les bélugas plongeaient plus en profondeur dans l’est de la mer de Beaufort que dans l’ouest de la mer de Beaufort ou dans la mer des Tchouktches. Les profondeurs auxquelles les bélugas plongent le plus souvent dans le canyon Barrow et le long du rebord continental de Beaufort (de 200 à 300 m) correspondent à la limite où l’eau plus froide du Pacifique se superpose à l’eau plus chaude de l’Atlantique, là où la morue polaire (Boreogadus saida) est plus dense. Dans le bassin arctique, la profondeur des plongées suggère que les bélugas s’alimentent surtout dans la couche tempérée d’eau de l’Atlantique (~200 à 1 000 m)

What's in a heuristic? Commentary on Sunstein, C.

The term “moral heuristic” as used by Sunstein seeks to bring together various traditions. However, there are significant differences between uses of the term “heuristic” in the cognitive and the social psychological research, and these differences are accompanied by very distinct evidential criteria. We suggest the term “moral heuristic” should refer to processes, which means that further evidence is required

Galactic Cosmic Radiation Leads to Cognitive Impairment and Increased Aβ Plaque Accumulation in a Mouse Model of Alzheimer’s Disease

Galactic Cosmic Radiation consisting of high-energy, high-charged (HZE) particles poses a significant threat to future astronauts in deep space. Aside from cancer, concerns have been raised about late degenerative risks, including effects on the brain. In this study we examined the effects of $^{56}$Fe particle irradiation in an APP/PS1 mouse model of Alzheimer’s disease (AD). We demonstrated 6 months after exposure to 10 and 100 cGy $^{56}$Fe radiation at 1 GeV/µ, that APP/PS1 mice show decreased cognitive abilities measured by contextual fear conditioning and novel object recognition tests. Furthermore, in male mice we saw acceleration of Aβ plaque pathology using Congo red and 6E10 staining, which was further confirmed by ELISA measures of Aβ isoforms. Increases were not due to higher levels of amyloid precursor protein (APP) or increased cleavage as measured by levels of the β C-terminal fragment of APP. Additionally, we saw no change in microglial activation levels judging by CD68 and Iba-1 immunoreactivities in and around Aβ plaques or insulin degrading enzyme, which has been shown to degrade Aβ. However, immunohistochemical analysis of ICAM-1 showed evidence of endothelial activation after 100 cGy irradiation in male mice, suggesting possible alterations in Aβ trafficking through the blood brain barrier as a possible cause of plaque increase. Overall, our results show for the first time that HZE particle radiation can increase Aβ plaque pathology in an APP/PS1 mouse model of AD

Spot and Cumulative Urine Samples Are Suitable Replacements for 24-Hour Urine Collections for Objective Measures of Dietary Exposure in Adults Using Metabolite Biomarkers

BACKGROUND: Measurement of multiple food intake exposure biomarkers in urine may offer an objective method for monitoring diet. The potential of spot and cumulative urine samples that have reduced burden on participants as replacements for 24-h urine collections has not been evaluated. OBJECTIVE: The aim of this study was to determine the utility of spot and cumulative urine samples for classifying the metabolic profiles of people according to dietary intake when compared with 24-h urine collections in a controlled dietary intervention study. METHODS: Nineteen healthy individuals (10 male, 9 female, aged 21-65 y, BMI 20-35 kg/m2) each consumed 4 distinctly different diets, each for 1 wk. Spot urine samples were collected ∼2 h post meals on 3 intervention days/wk. Cumulative urine samples were collected daily over 3 separate temporal periods. A 24-h urine collection was created by combining the 3 cumulative urine samples. Urine samples were analyzed with metabolite fingerprinting by both high-resolution flow infusion electrospray mass spectrometry (FIE-HRMS) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Concentrations of dietary intake biomarkers were measured with liquid chromatography triple quadrupole mass spectrometry and by integration of 1H-NMR data. RESULTS: Cross-validation modeling with 1H-NMR and FIE-HRMS data demonstrated the power of spot and cumulative urine samples in predicting dietary patterns in 24-h urine collections. Particularly, there was no significant loss of information when post-dinner (PD) spot or overnight cumulative samples were substituted for 24-h urine collections (classification accuracies of 0.891 and 0.938, respectively). Quantitative analysis of urine samples also demonstrated the relation between PD spot samples and 24-h urines for dietary exposure biomarkers. CONCLUSIONS: We conclude that PD spot urine samples are suitable replacements for 24-h urine collections. Alternatively, cumulative samples collected overnight predict similarly to 24-h urine samples and have a lower collection burden for participants

Integrated Analytical and Statistical Two-Dimensional Spectroscopy Strategy for Metabolite Identification: Application to Dietary Biomarkers

A major purpose of exploratory metabolic profiling is for the identification of molecular species that are statistically associated with specific biological or medical outcomes; unfortunately the structure elucidation process of unknowns is often a major bottleneck in this process. We present here new holistic strategies that combine different statistical spectroscopic and analytical techniques to improve and simplify the process of metabolite identification. We exemplify these strategies using study data collected as part of a dietary intervention to improve health and which elicits a relatively subtle suite of changes from complex molecular profiles. We identify three new dietary biomarkers related to the consumption of peas (N-methyl nicotinic acid), apples (rhamnitol) and onions (N-acetyl-S-(1Z)-propenyl-cysteine-sulfoxide) that can be used to enhance dietary assessment and assess adherence to diet. As part of the strategy, we introduce a new probabilistic statistical spectroscopy tool, RED-STORM (Resolution EnhanceD SubseT Optimization by Reference Matching), that uses 2D J-resolved ¹H-NMR spectra for enhanced information recovery using the Bayesian paradigm to extract a subset of spectra with similar spectral signatures to a reference. RED-STORM provided new information for subsequent experiments (e.g. 2D-NMR spectroscopy, Solid-Phase Extraction, Liquid Chromatography prefaced Mass Spectrometry) used to ultimately identify an unknown compound. In summary, we illustrate the benefit of acquiring J-resolved experiments alongside conventional 1D ¹H-NMR as part of routine metabolic profiling in large datasets and show that application of complementary statistical and analytical techniques for the identification of unknown metabolites can be used to save valuable time and resource

A Standardized Strategy for Simultaneous Quantification of Urine Metabolites to Validate Development of a Biomarker Panel Allowing Comprehensive Assessment of Dietary Exposure

SCOPE: Metabolites derived from individual foods found in human biofluids after consumption could provide objective measures of dietary intake. For comprehensive dietary assessment, quantification methods would need to manage the structurally diverse mixture of target metabolites present at a wide concentration range. METHODS & RESULTS: We developed a strategy for selection of candidate dietary exposure biomarkers, providing comprehensive coverage. An analytical method for 62 food biomarkers was validated by extensive analysis of chromatographic and ionization behaviour characteristics using triple quadrupole mass spectrometry. We used urine samples from two food intervention studies: one controlled, inpatient study (n = 19) and the other a free-living study where individuals (n = 15) were provided with food as a series of menu plans. As proof-of-principle, we demonstrated that the biomarker panel could discriminate between menu plans by detecting distinctive changes in the concentration in urine of targeted metabolites. We showed quantitative relationships between four biomarker concentrations in urine and dietary intake. CONCLUSIONS: We have demonstrated design concepts for an analytical strategy allowing simultaneous quantification of a comprehensive panel of chemically-diverse biomarkers of a wide range of commonly-consumed foods. We propose that integration of self-reported dietary recording tools with biomarker approaches will provide more robust assessment of dietary exposure. This article is protected by copyright. All rights reserved

An Analytical Pipeline for Quantitative Characterization of Dietary Intake:Application To Assess Grape Intake

Lack of accurate dietary assessment in free-living populations requires discovery of new biomarkers reflecting food intake qualitatively and quantitatively to objectively evaluate effects of diet on health. We provide a proof-of-principle for an analytical pipeline to identify quantitative dietary biomarkers. Tartaric acid was identified by nuclear magnetic resonance spectroscopy as a dose-responsive urinary biomarker of grape intake and subsequently quantified in volunteers following a series of 4-day dietary interventions incorporating 0 g/day, 50 g/day, 100 g/day, and 150 g/day of grapes in standardized diets from a randomized controlled clinical trial. Most accurate quantitative predictions of grape intake were obtained in 24 h urine samples which have the strongest linear relationship between grape intake and tartaric acid excretion (r² = 0.90). This new methodological pipeline for estimating nutritional intake based on coupling dietary intake information and quantified nutritional biomarkers was developed and validated in a controlled dietary intervention study, showing that this approach can improve the accuracy of estimating nutritional intakes