Factors affecting the determination of threshold doses for allergenic foods: How much is too much?

Background: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. Objective: We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. Methods: In September 1999,12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. Results: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows\u27 milk, and egg; limited data were available for other foods, such as fish and mustard. Conclusions: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed

Newtonian Cosmology in Lagrangian Formulation: Foundations and Perturbation Theory

The ``Newtonian'' theory of spatially unbounded, self--gravitating, pressureless continua in Lagrangian form is reconsidered. Following a review of the pertinent kinematics, we present alternative formulations of the Lagrangian evolution equations and establish conditions for the equivalence of the Lagrangian and Eulerian representations. We then distinguish open models based on Euclidean space $\R^3$ from closed models based (without loss of generality) on a flat torus \T^3. Using a simple averaging method we show that the spatially averaged variables of an inhomogeneous toroidal model form a spatially homogeneous ``background'' model and that the averages of open models, if they exist at all, in general do not obey the dynamical laws of homogeneous models. We then specialize to those inhomogeneous toroidal models whose (unique) backgrounds have a Hubble flow, and derive Lagrangian evolution equations which govern the (conformally rescaled) displacement of the inhomogeneous flow with respect to its homogeneous background. Finally, we set up an iteration scheme and prove that the resulting equations have unique solutions at any order for given initial data, while for open models there exist infinitely many different solutions for given data.Comment: submitted to G.R.G., TeX 30 pages; AEI preprint 01

Population Dynamics and Angler Exploitation of the Unique Muskellunge Population in Shoepack Lake, Voyageurs National Park, Minnesota

A unique population of muskellunge Esox masquinongy inhabits Shoepack Lake in Voyageurs National Park, Minnesota. Little is known about its status, dynamics, and angler exploitation, and there is concern for the long-term viability of this population. We used intensive sampling and mark–recapture methods to quantify abundance, survival, growth, condition, age at maturity and fecundity and angler surveys to quantify angler pressure, catch rates, and exploitation. During our study, heavy rain washed out a dam constructed by beavers Castor canadensis which regulates the water level at the lake outlet, resulting in a nearly 50% reduction in surface area. We estimated a population size of 1,120 adult fish at the beginning of the study. No immediate reduction in population size was detected in response to the loss of lake area, although there was a gradual, but significant, decline in population size over the 2-year study. Adults grew less than 50 mm per year, and relative weight (W r) averaged roughly 80. Anglers were successful in catching, on average, two fish during a full day of angling, but harvest was negligible. Shoepack Lake muskellunge exhibit much slower growth rates and lower condition, but much higher densities and angler catch per unit effort (CPUE), than other muskellunge populations. The unique nature, limited distribution, and location of this population in a national park require special consideration for management. The results of this study provide the basis for assessing the long-term viability of the Shoepack Lake muskellunge population through simulations of long-term population dynamics and genetically effective population size

Measuring the gravitational field in General Relativity: From deviation equations and the gravitational compass to relativistic clock gradiometry

How does one measure the gravitational field? We give explicit answers to this fundamental question and show how all components of the curvature tensor, which represents the gravitational field in Einstein's theory of General Relativity, can be obtained by means of two different methods. The first method relies on the measuring the accelerations of a suitably prepared set of test bodies relative to the observer. The second methods utilizes a set of suitably prepared clocks. The methods discussed here form the basis of relativistic (clock) gradiometry and are of direct operational relevance for applications in geodesy.Comment: To appear in "Relativistic Geodesy: Foundations and Application", D. Puetzfeld et. al. (eds.), Fundamental Theories of Physics, Springer 2018, 52 pages, in print. arXiv admin note: text overlap with arXiv:1804.11106, arXiv:1511.08465, arXiv:1805.1067

Synthesis and spectroscopic identification of ethylidyne adsorbed on Ni(111)&perp

The interaction of ethylene adsorbed on Ni(111) with gas-phase H atoms has been investigated. The major adsorbed reaction product is identified by high-resolution electron energy loss spectroscopy to be ethylidyne (C−CH3). This study is the first direct spectroscopic observation of a C−CH3 species adsorbed on Ni in an ultrahigh-vacuum environment. Spectra of four isotopomers, C−CH3, 13C−13CH3, C−CD3, and 13C−13CD3, are reported, and a complete and consistent vibrational assignment of their fundamental modes is presented. Based on this assignment, a force field is derived from the measured vibrational frequencies using a normal-modes analysis and is found to be in good agreement with that deduced from IR spectra of an ethylidyne species in an organometallic complex. Inspection of the eigenvectors of the normal-mode displacements reveals that substantial mixing of harmonic bond motions is the origin of the unusual upshift in frequency of the C−C stretching mode upon deuteration. A quantitative determination of the relative dynamic bond dipole moments demonstrates that the changes in intensity and dipole activity of the C−C stretching and symmetric CH3 deformation modes upon deuteration, phenomena common to all C−CD3 spectra, also arise from extensive mixing of bond motions. A detailed analysis of the spectra strongly suggests a C3v or C3 local environment for ethylidyne and a 3-fold hollow adsorption site

Small neuron-derived extracellular vesicles from individuals with down syndrome propagate tau pathology in the wildtype mouse brain

Altres ajuts: National Institutes of Health (R01AG070153/R21AG056974, RF1AG061566); Bright Focus foundation (CA2018010).Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS contains p-Tau at an early age. The goal of the study was to investigate whether NDEVs isolated from the blood of individuals with DS can spread Tau pathology in the brain of wildtype mice. We purified NDEVs from the plasma of patients with DS-AD and controls and injected small quantities using stereotaxic surgery into the dorsal hippocam-pus of adult wildtype mice. Seeding competent Tau conformers were amplified in vitro from DS-AD NDEVs but not NDEVs from controls. One month or 4 months post-injection, we examined Tau pathology in mouse brains. We found abundant p-Tau immunostaining in the hippocampus of the mice injected with DS-AD NDEVs compared to injections of age-matched control NDEVs. Double labeling with neuronal and glial markers showed that p-Tau staining was largely found in neurons and, to a lesser extent, in glial cells and that p-Tau immunostaining was spreading along the corpus callosum and the medio-lateral axis of the hippocampus. These studies demonstrate that NDEVs from DS-AD patients exhibit Tau seeding capacity and give rise to tangle-like intracellular inclusions

Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain

Individuals with Down syndrome (DS) exhibit Alzheimer’s disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS contains p-Tau at an early age. The goal of the study was to investigate whether NDEVs isolated from the blood of individuals with DS can spread Tau pathology in the brain of wildtype mice. We purified NDEVs from the plasma of patients with DS-AD and controls and injected small quantities using stereotaxic surgery into the dorsal hippocampus of adult wildtype mice. Seeding competent Tau conformers were amplified in vitro from DS-AD NDEVs but not NDEVs from controls. One month or 4 months post-injection, we examined Tau pathology in mouse brains. We found abundant p-Tau immunostaining in the hippocampus of the mice injected with DS-AD NDEVs compared to injections of age-matched control NDEVs. Double labeling with neuronal and glial markers showed that p-Tau staining was largely found in neurons and, to a lesser extent, in glial cells and that p-Tau immunostaining was spreading along the corpus callosum and the medio-lateral axis of the hippocampus. These studies demonstrate that NDEVs from DS-AD patients exhibit Tau seeding capacity and give rise to tangle-like intracellular inclusions