Respiratory epithelial cells require Toll-like receptor 4 for induction of Human β-defensin 2 by Lipopolysaccharide

BACKGROUND: The respiratory epithelium is a major portal of entry for pathogens and employs innate defense mechanisms to prevent colonization and infection. Induced expression of human β-defensin 2 (HBD2) represents a direct response by the epithelium to potential infection. Here we provide evidence for the critical role of Toll-like receptor 4 (TLR4) in lipopolysaccharide (LPS)-induced HBD2 expression by human A549 epithelial cells. METHODS: Using RTPCR, fluorescence microscopy, ELISA and luciferase reporter gene assays we quantified interleukin-8, TLR4 and HBD2 expression in unstimulated or agonist-treated A549 and/or HEK293 cells. We also assessed the effect of over expressing wild type and/or mutant TLR4, MyD88 and/or Mal transgenes on LPS-induced HBD2 expression in these cells. RESULTS: We demonstrate that A549 cells express TLR4 on their surface and respond directly to Pseudomonas LPS with increased HBD2 gene and protein expression. These effects are blocked by a TLR4 neutralizing antibody or functionally inactive TLR4, MyD88 and/or Mal transgenes. We further implicate TLR4 in LPS-induced HBD2 production by demonstrating HBD2 expression in LPS non-responsive HEK293 cells transfected with a TLR4 expression plasmid. CONCLUSION: This data defines an additional role for TLR4 in the host defense in the lung

Search for Anisotropy of Ultra-High Energy Cosmic Rays with the Telescope Array Experiment

We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E>57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure of the Universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the Universe (the LSS hypothesis), while the event set with E>10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis.Comment: 10 pages, 9 figure

Persistently Elevated Right Ventricular Index of Myocardial Performance in Preterm Infants with Incipient Bronchopulmonary Dysplasia

OBJECTIVES: Elevated pulmonary vascular resistance occurs during the first days after birth in all newborn infants and persists in infants at risk for bronchopulmonary dysplasia (BPD). It is difficult to measure in a non-invasive fashion. We assessed the usefulness of the right ventricular index of myocardial performance (RIMP) to estimate pulmonary vascular resistance in very low birth weight infants. STUDY DESIGN: Prospective echocardiography on day of life (DOL) 2, 7, 14, and 28 in 121 preterm infants (median [quartiles] gestational age 28 [26]-[29] weeks, birth weight 998 [743-1225] g) of whom 36 developed BPD (oxygen supplementation at 36 postmenstrual weeks). RESULTS: RIMP derived by conventional pulsed Doppler technique was unrelated to heart rate or mean blood pressure. RIMP on DOL 2 was similar in infants who subsequently did (0.39 [0.33-0.55]) and did not develop BPD (0.39 [0.28-0.51], p = 0.467). RIMP declined steadily in non-BPD infants but not in BPD infants (DOL 7: 0.31[0.22-0.39] vs. 0.35[0.29-0.48], p = 0.014; DOL 14: 0.23[0.17-0.30] vs. 0.35[0.25-0.43], p<0.001; DOL 28: 0.21[0.15-0.28] vs. 0.31 [0.21-0.35], p = 0.015). CONCLUSIONS: In preterm infants, a decline in RIMP after birth was not observed in those with incipient BPD. The pattern of RIMP measured in preterm infants is commensurate with that of pulmonary vascular resistance

Upper limit on the flux of photons with energies above 10(19) eV using the Telescope Array surface detector

We search for ultra-high energy photons by analyzing geometrical properties of shower fronts of events registered by the Telescope Array surface detector. By making use of an event-by-event statistical method, we derive upper limits on the absolute flux of primary photons with energies above 1019, 1019.5, and 1020 eV based on the first three years of data takenopen4

CORRELATIONS OF THE ARRIVAL DIRECTIONS OF ULTRA-HIGH ENERGY COSMIC RAYS WITH EXTRAGALACTIC OBJECTS AS OBSERVED BY THE TELESCOPE ARRAY EXPERIMENT

We search for correlations between the positions of extragalactic objects and the arrival directions of ultra-high energy cosmic rays (UHECRs) with primary energy E ??? 40 EeV as observed by the surface detector array of the Telescope Array (TA) experiment during the first 40 months of operation. We examine several public astronomical object catalogs, including the Veron-Cetty and Veron catalog of active galactic nuclei. We count the number of TA events correlated with objects in each catalog as a function of three parameters: the maximum angular separation between a TA event and an object, the minimum energy of the events, and the maximum redshift of the objects. We determine the combination of these parameters that maximizes the correlations, and we calculate the probability of having the same levels of correlations from an isotropic distribution of UHECR arrival directions. No statistically significant correlations are found when penalties for scanning over the above parameters and for searching in several catalogs are taken into account.open4

The Cosmic Ray Energy Spectrum Observed with the Surface Detector of the Telescope Array Experiment

The Telescope Array (TA) collaboration has measured the energy spectrum of ultra-high energy cosmic rays with primary energies above 1.6 x 10^(18) eV. This measurement is based upon four years of observation by the surface detector component of TA. The spectrum shows a dip at an energy of 4.6 x 10^(18) eV and a steepening at 5.4 x 10^(19) eV which is consistent with the expectation from the GZK cutoff. We present the results of a technique, new to the analysis of ultra-high energy cosmic ray surface detector data, that involves generating a complete simulation of ultra-high energy cosmic rays striking the TA surface detector. The procedure starts with shower simulations using the CORSIKA Monte Carlo program where we have solved the problems caused by use of the "thinning" approximation. This simulation method allows us to make an accurate calculation of the acceptance of the detector for the energies concerned.Comment: Accepted for publication by Astrophysical Journal Letter

The surface detector array of the Telescope Array experiment

The Telescope Array (TA) experiment, located in the western desert of Utah,USA, is designed for observation of extensive air showers from extremely high energy cosmic rays. The experiment has a surface detector array surrounded by three fluorescence detectors to enable simultaneous detection of shower particles at ground level and fluorescence photons along the shower track. The TA surface detectors and fluorescence detectors started full hybrid observation in March, 2008. In this article we describe the design and technical features of the TA surface detector.Comment: 32 pages, 17 figure

New air fluorescence detectors employed in the Telescope Array experiment

Since 2007, the Telescope Array (TA) experiment, based in Utah, USA, has been observing ultra high energy cosmic rays to understand their origins. The experiment involves a surface detector (SD) array and three fluorescence detector (FD) stations. FD stations, installed surrounding the SD array, measure the air fluorescence light emitted from extensive air showers (EASs) for precise determination of their energies and species. The detectors employed at one of the three FD stations were relocated from the High Resolution Fly's Eye experiment. At the other two stations, newly designed detectors were constructed for the TA experiment. An FD consists of a primary mirror and a camera equipped with photomultiplier tubes. To obtain the EAS parameters with high accuracies, understanding the FD optical characteristics is important. In this paper, we report the characteristics and installation of new FDs and the performances of the FD components. The results of the monitored mirror reflectance during the observation time are also described in this report.Comment: 44 pages, 23 figures, submitted to NIM-