Modeling Effective Dosages in Hormetic Dose-Response Studies

BACKGROUND: Two hormetic modifications of a monotonically decreasing log-logistic dose-response function are most often used to model stimulatory effects of low dosages of a toxicant in plant biology. As just one of these empirical models is yet properly parameterized to allow inference about quantities of interest, this study contributes the parameterized functions for the second hormetic model and compares the estimates of effective dosages between both models based on 23 hormetic data sets. Based on this, the impact on effective dosage estimations was evaluated, especially in case of a substantially inferior fit by one of the two models. METHODOLOGY/PRINCIPAL FINDINGS: The data sets evaluated described the hormetic responses of four different test plant species exposed to 15 different chemical stressors in two different experimental dose-response test designs. Out of the 23 data sets, one could not be described by any of the two models, 14 could be better described by one of the two models, and eight could be equally described by both models. In cases of misspecification by any of the two models, the differences between effective dosages estimates (0-1768%) greatly exceeded the differences observed when both models provided a satisfactory fit (0-26%). This suggests that the conclusions drawn depending on the model used may diverge considerably when using an improper hormetic model especially regarding effective dosages quantifying hormesis. CONCLUSIONS/SIGNIFICANCE: The study showed that hormetic dose responses can take on many shapes and that this diversity can not be captured by a single model without risking considerable misinterpretation. However, the two empirical models considered in this paper together provide a powerful means to model, prove, and now also to quantify a wide range of hormetic responses by reparameterization. Despite this, they should not be applied uncritically, but after statistical and graphical assessment of their adequacy

A Conserved Mechanism for Hormesis in Molecular Systems

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this case, hormesis can be observed if simultaneous binding of substrate and competitor enhances a response of the homo-multimer. We characterized this mechanism of hormesis in binding experiments that analyzed the interaction of homotrimeric proliferating cell nuclear antigen (PCNA) with uracil DNA glycosylase (UNG2) and a fluorescein-labeled peptide. Additionally, the basic features of this molecular mechanism appear to be conserved with at least two enzymes that are stimulated by low doses of inhibitor: dimeric BRAF and octameric glutamine synthetase 2 (GS2). Identifying such molecular mechanisms of hormesis may help explain specific hormetic responses of cells and organisms treated with exogenous compounds

Report of the Working Group on the Composition of Ultra High Energy Cosmic Rays

For the first time a proper comparison of the average depth of shower maximum ($X_{\rm max}$) published by the Pierre Auger and Telescope Array Observatories is presented. The $X_{\rm max}$ distributions measured by the Pierre Auger Observatory were fit using simulated events initiated by four primaries (proton, helium, nitrogen and iron). The primary abundances which best describe the Auger data were simulated through the Telescope Array (TA) Middle Drum (MD) fluorescence and surface detector array. The simulated events were analyzed by the TA Collaboration using the same procedure as applied to their data. The result is a simulated version of the Auger data as it would be observed by TA. This analysis allows a direct comparison of the evolution of $\langle X_{\rm max} \rangle$ with energy of both data sets. The $\langle X_{\rm max} \rangle$ measured by TA-MD is consistent with a preliminary simulation of the Auger data through the TA detector and the average difference between the two data sets was found to be $(2.9 \pm 2.7\;(\text{stat.}) \pm 18\;(\text{syst.}))~\text{g/cm}^2$.Comment: To appear in the Proceedings of the UHECR workshop, Springdale USA, 201

Measurement of air and nitrogen fluorescence light yields induced by electron beam for UHECR experiments

Most of the Ultra High Energy Cosmic Ray (UHECR) experiments and projects (HiRes, AUGER, TA, EUSO, TUS,...) use air fluorescence to detect and measure extensive air showers (EAS). The precise knowledge of the Fluorescence Light Yield (FLY) is of paramount importance for the reconstruction of UHECR. The MACFLY - Measurement of Air Cherenkov and Fluorescence Light Yield - experiment has been designed to perform such FLY measurements. In this paper we will present the results of FLY in the 290-440 nm wavelength range for dry air and pure nitrogen, both excited by electrons with energy of 1.5 MeV, 20 GeV and 50 GeV. The experiment uses a 90Sr radioactive source for low energy measurement and a CERN SPS electron beam for high energy. We find that the FLY is proportional to the deposited energy (E_d) in the gas and we show that the air fluorescence properties remain constant independently of the electron energy. At the reference point: atmospheric dry air at 1013 hPa and 23C, the ratio FLY/E_d=17.6 photon/MeV with a systematic error of 13.2%.Comment: 19 pages, 8 figures. Accepted for publication in Astroparticle Physic

Multiple Dendritic Cell Populations Activate CD4+ T Cells after Viral Stimulation

Dendritic cells (DC) are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8α DC play a prominent, and sometimes exclusive, role in driving amplification of CD8+ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4+ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4+ and CD8+ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8α DC populations in the amplification of CD8+ and CD4+ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8+ T cells are dominated by presentation of antigen by CD8α DC but can involve non-CD8α DC. In contrast, CD4+ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4+ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity

Air fluorescence measurements in the spectral range 300-420 nm using a 28.5 GeV electron beam

Measurements are reported of the yield and spectrum of fluorescence, excited by a 28.5 GeV electron beam, in air at a range of pressures of interest to ultra-high energy cosmic ray detectors. The wavelength range was 300 - 420 nm. System calibration has been performed using Rayleigh scattering of a nitrogen laser beam. In atmospheric pressure dry air at 304 K the yield is 20.8 +/- 1.6 photons per MeV.Comment: 29 pages, 10 figures. Submitted to Astroparticle Physic

Search for the Weak Decay of an H Dibaryon

We have searched for a neutral $H$ dibaryon decaying via $H\to\Lambda n$ and $H\to\Sigma^0 n$. Our search has yielded two candidate events from which we set an upper limit on the $H$ production cross section. Normalizing to the inclusive $\Lambda$ production cross section, we find $(d\sigma_H/d\Omega) / (d\sigma_\Lambda/d\Omega) < 6.3\times 10^{-6}$ at 90% C.L., for an $H$ of mass $\approx$ 2.15 GeV/$c^2$.Comment: 11 pages, 6 postscript figures, epsfig, aps, preprint, revte

The stable phases of the Cs2CuCl4-xBrx mixed systems

Starting from Cs2CuCl4 and Cs2CuBr4 our project focuses on the growth of the Cs2CuCl4-xBrx mixed crystals from aqueous solution and the investigation of the occurring structural variations. The well known orthorhombic structure (space group Pnma) of the end members of this system is interrupted within the intermediate composition range Cs2CuCl3Br1 - Cs2CuCl2Br2, if the growth takes place at room temperature. Within this range a new tetragonal phase is found (space group I4/mmm). However, in case the growth temperature will be increased to 50 {\deg}C, the existence of the orthorhombic structure can be extended over the whole Cs2CuCl4-xBrx mixed system. A detailed analysis of the composition dependence of the lattice parameters is used to draw conclusions on the incorporation of Cl- and Br-ions at different sites which is important for the magnetic interactions between the Cu-ions.Comment: 16 pages,8 figure