Avoiding false-positive signals with nuclease-vulnerable molecular beacons in single living cells

There have been a growing number of studies where molecular beacons (MBs) are used to image RNA expression in living cells; however, the ability to make accurate measurements can be hampered by the generation of false-positive signals resulting from non-specific interactions and/or nuclease degradation. In the present study, we found that such non-specific signals only arise in the nucleus of living cells. When MBs are retained in the cytoplasmic compartment, by linking them to quantum dots (QDs), false-positive signals are reduced to marginal levels. Consequently, MB–QD conjugates were used to measure the expression of the endogenous proto-oncogene c-myc in MCF-7 breast cancer cells by quantifying the total fluorescent signal emanating from individual cells. Upon the addition of tamoxifen, measurements of MB fluorescence indicated a 71% reduction in c-myc expression, which correlated well with RT-PCR measurements. Variations in MB fluorescence resulting from instrumental fluctuations were accounted for by imaging fluorescent calibration standards on a daily basis. Further, it was established that measurements of the total fluorescent signal were not sensitive to the focal plane. Overall, these results provide evidence that accurate measurements of RNA levels can be made when MBs are retained in the cytoplasm

The Cosmic-Ray Composition between 2 PeV and 2 EeV Observed with the TALE Detector in Monocular Mode

We report on a measurement of the cosmic-ray composition by the Telescope Array Low-energy Extension (TALE) air fluorescence detector (FD). By making use of the Cherenkov light signal in addition to air fluorescence light from cosmic-ray (CR)-induced extensive air showers, the TALE FD can measure the properties of the cosmic rays with energies as low as ∼2 PeV and exceeding 1 EeV. In this paper, we present results on the measurement of distributions of showers observed over this energy range. Data collected over a period of ∼4 yr were analyzed for this study. The resulting distributions are compared to the Monte Carlo (MC) simulated data distributions for primary cosmic rays with varying composition and a four-component fit is performed. The comparison and fit are performed for energy bins, of width 0.1 or 0.2 in, spanning the full range of the measured energies. We also examine the mean value as a function of energy for cosmic rays with energies greater than 1015.8 eV. Below 1017.3 eV, the slope of the mean as a function of energy (the elongation rate) for the data is significantly smaller than that of all elements in the models, indicating that the composition is becoming heavier with energy in this energy range. This is consistent with a rigidity-dependent cutoff of events from Galactic sources. Finally, an increase in the elongation rate is observed at energies just above 1017 eV, indicating another change in the cosmic-ray composition

Observation of variations in cosmic ray single count rates during thunderstorms and implications for large-scale electric field changes

We present the first observation by the Telescope Array Surface Detector (TASD) of the effect of thunderstorms on the development of cosmic ray single count rate intensity over a 700 km2 area. Observations of variations in the secondary low-energy cosmic ray counting rate, using the TASD, allow us to study the electric field inside thunderstorms, on a large scale, as it progresses on top of the 700 km2 detector, without dealing with the limitation of narrow exposure in time and space using balloons and aircraft detectors. In this work, variations in the cosmic ray intensity (single count rate) using the TASD, were studied and found to be on average at the ~(0.5-1)% and up to 2% level. These observations were found to be both in excess and in deficit. They were also found to be correlated with lightning in addition to thunderstorms. These variations lasted for tens of minutes; their footprint on the ground ranged from 6 km to 24 km in diameter and moved in the same direction as the thunderstorm. With the use of simple electric field models inside the cloud and between cloud to ground, the observed variations in the cosmic ray single count rate were recreated using CORSIKA simulations. Depending on the electric field model used and the direction of the electric field in that model, the electric field magnitude that reproduces the observed low-energy cosmic ray single count rate variations was found to be approximately between 0.2 GV-0.4 GV. This in turn allows us to get a reasonable insight on the electric field and its effect on cosmic ray air showers inside thunderstorms

Measurement of the proton-air cross section with Telescope Array\u27s Black Rock Mesa and Long Ridge fluorescence detectors, and surface array in hybrid mode

Ultrahigh energy cosmic rays provide the highest known energy source in the Universe to measure proton cross sections. Though conditions for collecting such data are less controlled than an accelerator environment, current generation cosmic ray observatories have large enough exposures to collect significant statistics for a reliable measurement for energies above what can be attained in the laboratory. Cosmic ray measurements of cross section use atmospheric calorimetry to measure depth of air shower maximum (Xmax), which is related to the primary particle\u27s energy and mass. The tail of the Xmax distribution is assumed to be dominated by showers generated by protons, allowing measurement of the inelastic proton-air cross section. In this work, the proton-air inelastic cross section measurement, σp-airinel, using data observed by Telescope Array\u27s Black Rock Mesa and Long Ridge fluorescence detectors and surface detector array in hybrid mode is presented. σp-airinel is observed to be 520.1±35.8[Stat]-42.9+25.3[Sys] mb at s=73 TeV. The total proton-proton cross section is subsequently inferred from Glauber formalism and is found to be σpptot=139.4-21.3+23.4[Stat]-25.4+15.7[Sys] mb

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

Observations of the Origin of Downward Terrestrial Gamma-Ray Flashes

In this paper we report the first close, high-resolution observations of downward-directed terrestrial gamma-ray flashes (TGFs) detected by the large-area Telescope Array cosmic ray observatory, obtained in conjunction with broadband VHF interferometer and fast electric field change measurements of the parent discharge. The results show that the TGFs occur during strong initial breakdown pulses (IBPs) in the first few milliseconds of negative cloud-to-ground and low-altitude intracloud flashes and that the IBPs are produced by a newly identified streamer-based discharge process called fast negative breakdown. The observations indicate the relativistic runaway electron avalanches (RREAs) responsible for producing the TGFs are initiated by embedded spark-like transient conducting events (TCEs) within the fast streamer system and potentially also by individual fast streamers themselves. The TCEs are inferred to be the cause of impulsive sub-pulses that are characteristic features of classic IBP sferics. Additional development of the avalanches would be facilitated by the enhanced electric field ahead of the advancing front of the fast negative breakdown. In addition to showing the nature of IBPs and their enigmatic sub-pulses, the observations also provide a possible explanation for the unsolved question of how the streamer to leader transition occurs during the initial negative breakdown, namely, as a result of strong currents flowing in the final stage of successive IBPs, extending backward through both the IBP itself and the negative streamer breakdown preceding the IBP

Indications of intermediate-scale anisotropy of cosmic rays with energy greater than 57 EeV in the northern sky measured with the surface detector of the Telescope Array experiment

We have searched for intermediate-scale anisotropy in the arrival directions of ultrahigh-energy cosmic rays with energies above 57 EeV in the northern sky using data collected over a 5 yr period by the surface detector of the Telescope Array experiment. We report on a cluster of events that we call the hotspot, found by oversampling using 20?? radius circles. The hotspot has a Li-Ma statistical significance of 5.1??, and is centered at R.A. = 146.??7, decl. = 43.??2. The position of the hotspot is about 19?? off of the supergalactic plane. The probability of a cluster of events of 5.1?? significance, appearing by chance in an isotropic cosmic-ray sky, is estimated to be 3.7 ?? 10-4 (3.4??).open2

Measurement of the proton-air cross section with Telescope Array's Middle Drum detector and surface array in hybrid mode

In this work we are reporting on the measurement of the proton-air inelastic cross section sigma(inel)(p-air) using the Telescope Array detector. Based on the measurement of the sigma(inel)(p-air), the proton-proton cross section sigma(p-p) value is also determined at root s = 95(-8)(+5) TeV. Detecting cosmic ray events at ultrahigh energies with the Telescope Array enables us to study this fundamental parameter that we are otherwise unable to access with particle accelerators. The data used in this report are the hybrid events observed by the Middle Drum fluorescence detector together with the surface array detector collected over five years. The value of the sigma(inel)(p-air) is found to be equal to 567.0 +/- 70.5[Stat](-25)(+29)[Sys] mb. The total proton-proton cross section is subsequently inferred from Glauber formalism and the Block, Halzen and Stanev QCD inspired fit and is found to be equal to 170(-44)(+48)[Stat](-17)(+19)[Sys] mb.open20