426 research outputs found

    The complexity of the California recall election

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    The October 7, 2003 California Recall Election strained California’s direct democracy. In recent California politics there has not been a statewide election conducted on such short notice; county election officials were informed on July 24 that the election would be held on October 7. Nor has California recently seen a ballot with so many candidates running for a single statewide office (see Mueller 1970). Under easy ballot access requirements, Secretary of State Kevin Shelley certified 135 candidates for the official ballot on August 13^1. In the recall, voters cast votes on (1) whether to recall Governor Davis from office, and (2) his possible successor. These two voting decisions were made independent by the federal district court’s decision on July 29. The court’s decision invalidated a state law requiring a vote on the recall question in order for a vote on the successor election to be counted (Partnoy et al. 2003). The abbreviated election calendar also led to many improvisations, including a dramatically reduced number of precinct poll sites throughout the state and the unprecedented ability of military personnel, their dependents, and civilians living overseas to return their absentee ballots by fax. These problems produced litigation and speculation that substantial problems would mar the election and throw the outcome of both the recall and a possible successor’s election into doubt. In the end, the litigation failed to stall the recall election, and the large final vote margins on both the recall question and the successor ballot seemingly overwhelmed Election Day problems. In this paper, we concentrate on some of the problems produced by the complexity of the recall election, but we do not attempt an exhaustive presentation of these problems. We focus on polling place problems on election day, the problems associated with translating the complicated recall election ballot into six languages, how the long ballot influenced voter behavior, and voter difficulties with the ballot measured with survey data. We conclude with a short discussion of the possible impact of these problems on the recall election

    Rational Voters and the Recall Election

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    The 2003 California recall election presented voters with a pair of choices. The first was whether or not to recall Gray Davis as Governor of the state. They were then faced with a list of 135 potential replacement candidates, one of whom would be chosen in the event Davis lost on the initial recall question. The two ballot questions were formally separate questions, but they were interrelated and conditional in nature. If I vote in favor of recalling Davis as Governor, whom should I support to replace him? Alternatively, voters who opposed recalling Davis as Governor had to decide who to vote for as replacement candidate to try to insure that, if Davis were recalled, an acceptable replacement candidate would be elected

    The Human Milk Oligosaccharides 3-FL, Lacto-N-Neotetraose, and LDFT Attenuate Tumor Necrosis Factor-alpha Induced Inflammation in Fetal Intestinal Epithelial Cells In Vitro through Shedding or Interacting with Tumor Necrosis Factor Receptor 1

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    Scope Human milk oligosaccharides (hMOs) can attenuate inflammation by modulating intestinal epithelial cells, but the mechanisms of action are not well-understood. Here, the effects of hMOs on tumor necrosis factor-alpha (TNF-alpha) induced inflammatory events in gut epithelial cells are studied. Methods and results The modulatory effects of 2'-fucosyllactose, 3-fucosyllactose (3-FL), 6'-sialyllactose, lacto-N-tetraose, lacto-N-neotetraose (LNnT), lactodifucotetraose (LDFT), and lacto-N-triaose (LNT2) on immature (FHs 74 Int) and adult (T84) intestinal epithelial cells with or without TNF-alpha are determined. Interleukin-8 (IL-8) secretion in FHs 74 Int and T84 are quantified to determine hMO induced attenuation of inflammatory events by ELISA. 3-FL, LNnT, and LDFT significantly attenuate TNF-alpha induced inflammation in FHs 74 Int, while LNT2 induces IL-8 secretion in T84. In addition, microscale thermophoresis assays and ELISA are used to study the possible mechanisms of interaction between effective hMOs and tumor necrosis factor receptor 1 (TNFR1). 3-FL, LNnT, and LDFT exert TNFR1 ectodomain shedding while LNnT also shows binding affinity to TNFR1 with a Kd of 900 +/- 660 nM. Conclusion The findings indicate that specific hMO types attenuate TNF-alpha induced inflammation in fetal gut epithelial cells through TNFR1 in a hMO structure-dependent fashion suggest possibilities to apply hMOs in management of TNF-alpha dependent diseases

    A simple microscopy setup for visualizing cellular responses to DNA damage at particle accelerator facilities

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    Cellular responses to DNA double-strand breaks (DSBs) not only promote genomic integrity in healthy tissues, but also largely determine the efficacy of many DNA-damaging cancer treatments, including X-ray and particle therapies. A growing body of evidence suggests that activation of the mechanisms that detect, signal and repair DSBs may depend on the complexity of the initiating DNA lesions. Studies focusing on this, as well as on many other radiobiological questions, require reliable methods to induce DSBs of varying complexity, and to visualize the ensuing cellular responses. Accelerated particles of different energies and masses are exceptionally well suited for this task, due to the nature of their physical interactions with the intracellular environment, but visualizing cellular responses to particle-induced damage - especially in their early stages - at particle accelerator facilities, remains challenging. Here we describe a straightforward approach for real-time imaging of early response to particle-induced DNA damage. We rely on a transportable setup with an inverted fluorescence confocal microscope, tilted at a small angle relative to the particle beam, such that cells can be irradiated and imaged without any microscope or beamline modifications. Using this setup, we image and analyze the accumulation of fluorescently-tagged MDC1, RNF168 and 53BP1—key factors involved in DSB signalling—at DNA lesions induced by 254 MeV α-particles. Our results provide a demonstration of technical feasibility and reveal asynchronous initiation of accumulation of these proteins at different individual DSBs

    Dynamics of liquid 4He in Vycor

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    We have measured the dynamic structure factor of liquid 4He in Vycor using neutron inelastic scattering. Well-defined phonon-roton (p-r) excitations are observed in the superfluid phase for all wave vectors 0.3 < Q < 2.15. The p-r energies and lifetimes at low temperature (T = 0.5 K) and their temperature dependence are the same as in bulk liquid 4He. However, the weight of the single p-r component does not scale with the superfluid fraction (SF) as it does in the bulk. In particular, we observe a p-r excitation between T_c = 1.952 K, where SF = 0, and T_(lambda)=2.172 K of the bulk. This suggests, if the p-r excitation intensity scales with the Bose condensate, that there is a separation of the Bose-Einstein condensation temperature and the superfluid transition temperature T_c of 4He in Vycor. We also observe a two-dimensional layer mode near the roton wave vector. Its dispersion is consistent with specific heat and SF measurements and with layer modes observed on graphite surfaces.Comment: 3 pages, 4 figure

    Investigating the lateral dose response functions of point detectors in proton beams

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    Objective Point detector measurements in proton fields are perturbed by the volume effect originating from geometrical volume-averaging within the extended detector's sensitive volume and density perturbations by non-water equivalent detector components. Detector specific lateral dose response functions K(x) can be used to characterize the volume effect within the framework of a mathematical convolution model, where K(x) is the convolution kernel transforming the true dose profile D(x) into the measured signal profile of a detector M(x). The aim of this work is to investigate K(x) for detectors in proton beams. Approach The K(x) for five detectors were determined by iterative deconvolution of measurements of D(x) and M(x) profiles at 2 cm water equivalent depth of a narrow 150 MeV proton beam. Monte Carlo simulations were carried out for two selected detectors to investigate a potential energy dependence, and to study the contribution of volume-averaging and density perturbation to the volume effect. Main results The Monte Carlo simulated and experimentally determined K(x) agree within 2.1% of the maximum value. Further simulations demonstrate that the main contribution to the volume effect is volume-averaging. The results indicate that an energy or depth dependence of K(x) is almost negligible in proton beams. While the signal reduction from a Semiflex 3D ionization chamber in the center of a gaussian shaped field with 2 mm sigma is 32% for photons, it is 15% for protons. When measuring the field with a microDiamond the trend is less pronounced and reversed with a signal reduction for protons of 3.9% and photons of 1.9%. Significance The determined K(x) can be applied to characterize the influence of the volume effect on detectors measured signal profiles at all clinical proton energies and measurement depths. The functions can be used to derive the actual dose distribution from point detector measurements

    Towards Next-Generation Sequencing (NGS)-Based Newborn Screening:A Technical Study to Prepare for the Challenges Ahead

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    Newborn screening (NBS) aims to identify neonates with severe conditions for whom immediate treatment is required. Currently, a biochemistry-first approach is used to identify these disorders, which are predominantly inherited metalbolic disorders (IMD). Next-generation sequencing (NGS) is expected to have some advantages over the current approach, for example the ability to detect IMDs that meet all screening criteria but lack an identifiable biochemical footprint. We have now designed a technical study to explore the use of NGS techniques as a first-tier approach in NBS. Here, we describe the aim and set-up of the NGS-first for the NBS (NGSf4NBS) project, which will proceed in three steps. In Step 1, we will identify IMDs eligible for NGS-first testing, based on treatability. In Step 2, we will investigate the feasibility, limitations and comparability of different technical NGS approaches and analysis workflows for NBS, eventually aiming to develop a rapid NGS-based workflow. Finally, in Step 3, we will prepare for the incorporation of this workflow into the existing Dutch NBS program and propose a protocol for referral of a child after a positive NGS test result. The results of this study will be the basis for an additional analytical route within NBS that will be further studied for its applicability within the NBS program, e.g., regarding the ethical, legal, financial and social implications.</p

    Modeling focal epileptic activity in the Wilson-Cowan model with depolarization block

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    Measurements of neuronal signals during human seizure activity and evoked epileptic activity in experimental models suggest that, in these pathological states, the individual nerve cells experience an activity driven depolarization block, i.e. they saturate. We examined the effect of such a saturation in the Wilson–Cowan formalism by adapting the nonlinear activation function; we substituted the commonly applied sigmoid for a Gaussian function. We discuss experimental recordings during a seizure that support this substitution. Next we perform a bifurcation analysis on the Wilson–Cowan model with a Gaussian activation function. The main effect is an additional stable equilibrium with high excitatory and low inhibitory activity. Analysis of coupled local networks then shows that such high activity can stay localized or spread. Specifically, in a spatial continuum we show a wavefront with inhibition leading followed by excitatory activity. We relate our model simulations to observations of spreading activity during seizures
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