Interrelationship between Dendritic Cell Trafficking and Francisella tularensis Dissemination following Airway Infection

Francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. Nevertheless, evidence for its in vivo intracellular residence is less conclusive. Dendritic cells (DC) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. Here, we focus on the in vivo interactions of F. tularensis with DC following airway infection of mice. Lethal airway infection of mice with the live vaccine strain (LVS) results in trafficking of a CD11bhigh/CD11cmed/autofluorescencelow DC subset from the respiratory tract to the draining mediastinal lymph node (MdLN). Simultaneously, a rapid, massive bacterial colonization of the MdLN occurs, characterized by large bacterial foci formation. Analysis of bacteria in the MdLN revealed a major population of extracellular bacteria, which co-exists with a substantial fraction of intracellular bacteria. The intracellular bacteria are viable and reside in cells sorted for DC marker expression. Moreover, in vivo vital staining experiments indicate that most of these intracellular bacteria (∼75%) reside in cells that have migrated from the airways to the MdLN after infection. The correlation between DC and bacteria accumulation in the MdLN was further demonstrated by manipulating DC migration to the MdLN through two independent pathways. Impairment of DC migration to the MdLN, either by a sphingosine-1-phosphate receptor agonist (FTY720) or by the D prostanoid receptor 1 agonist (BW245C), resulted in reduced bacterial colonization of MdLN. Moreover, BW245C treatment delayed the onset of morbidity and the time to death of the infected mice. Taken together, these results suggest that DC can serve as an inhabitation niche for F. tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment

Evaluating Effects of Divided Hemispheric Processing on Word Recognition in Foveal and Extrafoveal Displays: The Evidence from Arabic

Background: Previous studies have claimed that a precise split at the vertical midline of each fovea causes all words to the left and right of fixation to project to the opposite, contralateral hemisphere, and this division in hemispheric processing has considerable consequences for foveal word recognition. However, research in this area is dominated by the use of stimuli from Latinate languages, which may induce specific effects on performance. Consequently, we report two experiments using stimuli from a fundamentally different, non-Latinate language (Arabic) that offers an alternative way of revealing effects of split-foveal processing, if they exist. Methods and Findings: Words (and pseudowords) were presented to the left or right of fixation, either close to fixation and entirely within foveal vision, or further from fixation and entirely within extrafoveal vision. Fixation location and stimulus presentations were carefully controlled using an eye-tracker linked to a fixation-contingent display. To assess word recognition, Experiment 1 used the Reicher-Wheeler task and Experiment 2 used the lexical decision task. Results: Performance in both experiments indicated a functional division in hemispheric processing for words in extrafoveal locations (in recognition accuracy in Experiment 1 and in reaction times and error rates in Experiment 2) but no such division for words in foveal locations. Conclusions: These findings from a non-Latinate language provide new evidence that although a functional division i

Effective field theory analysis of the first LUX dark matter search

The Large Underground Xenon (LUX) dark matter search was a 250-kg active mass dual-phase time projection chamber that operated by detecting light and ionization signals from particles incident on a xenon target. In December 2015, LUX reported a minimum 90% upper C.L. of 6×10-46 cm2 on the spin-independent WIMP-nucleon elastic scattering cross section based on a 1.4×104 kg·day exposure in its first science run. Tension between experiments and the absence of a definitive positive detection suggest it would be prudent to search for WIMPs outside the standard spin-independent/spin-dependent paradigm. Recent theoretical work has identified a complete basis of 14 independent effective field theory (EFT) operators to describe WIMP-nucleon interactions. In addition to spin-independent and spin-dependent nuclear responses, these operators can produce novel responses such as angular-momentum-dependent and spin-orbit couplings. Here we report on a search for all 14 of these EFT couplings with data from LUX's first science run. Limits are placed on each coupling as a function of WIMP mass

Ultra-Low Energy Calibration of LUX Detector using 127^{127}Xe Electron Capture

We report an absolute calibration of the ionization yields(\textit{Q_y}) and fluctuations for electronic recoil events in liquid xenon at discrete energies between 186 eV and 33.2 keV. The average electric field applied across the liquid xenon target is 180 V/cm. The data are obtained using low energy $^{127}$Xe electron capture decay events from the 95.0-day first run from LUX (WS2013) in search of Weakly Interacting Massive Particles (WIMPs). The sequence of gamma-ray and X-ray cascades associated with $^{127}$I de-excitations produces clearly identified 2-vertex events in the LUX detector. We observe the K- (binding energy, 33.2 keV), L- (5.2 keV), M- (1.1 keV), and N- (186 eV) shell cascade events and verify that the relative ratio of observed events for each shell agrees with calculations. The N-shell cascade analysis includes single extracted electron (SE) events and represents the lowest-energy electronic recoil $\textit{in situ}$ measurements that have been explored in liquid xenon

Investigation of background electron emission in the LUX detector

Dual-phase xenon detectors, as currently used in direct detection dark matter experiments, have observed elevated rates of background electron events in the low energy region. While this background negatively impacts detector performance in various ways, its origins have only been partially studied. In this paper we report a systematic investigation of the electron pathologies observed in the LUX dark matter experiment. We characterize different electron populations based on their emission intensities and their correlations with preceding energy depositions in the detector. By studying the background under different experimental conditions, we identified the leading emission mechanisms, including photoionization and the photoelectric effect induced by the xenon luminescence, delayed emission of electrons trapped under the liquid surface, capture and release of drifting electrons by impurities, and grid electron emission. We discuss how these backgrounds can be mitigated in LUX and future xenon-based dark matter experiments

First direct detection constraint on mirror dark matter kinetic mixing using LUX 2013 data

We present the results of a direct detection search for mirror dark matter interactions, using data collected from the Large Underground Xenon experiment during 2013, with an exposure of 95 live-days × 118 kg. Here, the calculations of the mirror electron scattering rate in liquid xenon take into account the shielding effects from mirror dark matter captured within the Earth. Annual and diurnal modulation of the dark matter flux and atomic shell effects in xenon are also accounted for. Having found no evidence for an electron recoil signal induced by mirror dark matter interactions we place an upper limit on the kinetic mixing parameter over a range of local mirror electron temperatures between 0.1 and 0.6 keV. This limit shows significant improvement over the previous experimental constraint from orthopositronium decays and significantly reduces the allowed parameter space for the model. We exclude mirror electron temperatures above 0.3 keV at a 90% confidence level, for this model, and constrain the kinetic mixing below this temperature

An effective field theory analysis of the first LUX dark matter search

The Large Underground Xenon (LUX) dark matter search was a 250-kg active mass dual-phase time projection chamber that operated by detecting light and ionization signals from particles incident on a xenon target. In December 2015, LUX reported a minimum 90% upper C.L. of 6e-46 cm^2 on the spin-independent WIMP-nucleon elastic scattering cross section based on a 1.4e4 kg*day exposure in its first science run. Tension between experiments and the absence of a definitive positive detection suggest it would be prudent to search for WIMPs outside the standard spin-independent/spin-dependent paradigm. Recent theoretical work has identified a complete basis of 14 independent effective field theory (EFT) operators to describe WIMP-nucleon interactions. In addition to spin-independent and spin-dependent nuclear responses, these operators can produce novel responses such as angular-momentum-dependent and spin-orbit couplings. Here we report on a search for all 14 of these EFT couplings with data from LUX's first science run. Limits are placed on each coupling as a function of WIMP mass

Search for two neutrino double electron capture of ¹²⁴Xe and ¹²⁶Xe in the full exposure of the LUX detector

Two-neutrino double electron capture is a process allowed in the standard model of particle physics. This rare decay has been observed in 78Kr, 130Ba and more recently in 124Xe. In this publication we report on the search for this process in 124Xe and 126Xe using the full exposure of the large underground xenon (LUX) experiment, in a total of 27769.5 kg-days. No evidence of a signal was observed, allowing us to set 90% C.L. lower limits for the half-lives of these decays of 2.0 × 1021 years for 124Xe and 1.9 × 1021 years for 126Xe

Fast and flexible analysis of direct dark matter search data with machine learning

We present the results from combining machine learning with the profile likelihood fit procedure, using data from the Large Underground Xenon (LUX) dark matter experiment. This approach demonstrates reduction in computation time by a factor of 30 when compared with the previous approach, without loss of performance on real data. We establish its flexibility to capture nonlinear correlations between variables (such as smearing in light and charge signals due to position variation) by achieving equal performance using pulse areas with and without position-corrections applied. Its efficiency and scalability furthermore enables searching for dark matter using additional variables without significant computational burden. We demonstrate this by including a light signal pulse shape variable alongside more traditional inputs, such as light and charge signal strengths. This technique can be exploited by future dark matter experiments to make use of additional information, reduce computational resources needed for signal searches and simulations, and make inclusion of physical nuisance parameters in fits tractable