Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset

Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets

Rapid Reactivation of Extralymphoid CD4 T Cells during Secondary Infection

After infection, extralymphoid tissues are enriched with effector and memory T cells of a highly activated phenotype. The capacity for rapid effector cytokine response from extralymphoid tissue-memory T cells suggests these cells may perform a ‘sentinel’ function in the tissue. While it has been demonstrated that extralymphoid CD4+ T cells can directly respond to secondary infection, little is known about how rapidly this response is initiated, and how early activation of T cells in the tissue may affect the innate response to infection. Here we use a mouse model of secondary heterosubtypic influenza infection to show that CD4+ T cells in the lung airways are reactivated within 24 hours of secondary challenge. Airway CD4+ T cells initiate an inflammatory cytokine and chemokine program that both alters the composition of the early innate response and contributes to the reduction of viral titers in the lung. These results show that, unlike a primary infection, extralymphoid tissue-memory CD4+ T cells respond alongside the innate response during secondary infection, thereby shaping the overall immune profile in the airways. These data provide new insights into the role of extralymphoid CD4+ T cells during secondary immune responses

A search for ultrahigh-energy neutrinos associated with astrophysical sources using the third flight of ANITA

The ANtarctic Impulsive Transient Antenna (ANITA) long-duration balloon experiment is sensitive to interactions of ultrahigh-energy (E>1018 eV) neutrinos in the Antarctic ice sheet. The third flight of ANITA, lasting 22 days, began in December 2014. We develop a methodology to search for energetic neutrinos spatially and temporally coincident with potential source classes in ANITA data. This methodology is applied to several source classes: the potential IceCube-identified neutrino sources TXS 0506+056 and NGC 1068, flaring high-energy blazars reported by the Fermi All-Sky Variability Analysis, gamma-ray bursts, and supernovae. Among searches within the five source classes, one candidate was identified as associated with SN 2015D, although not at a statistically significant level. We proceed to place upper limits on the source classes. We further comment on potential application of this methodology to more sensitive future instruments

Characteristics of Four Upward-Pointing Cosmic-Ray-like Events Observed with ANITA

We report on four radio-detected cosmic-ray (CR) or CR-like events observed with the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload. Two of the four were previously identified as stratospheric CR air showers during the ANITA-I flight. A third stratospheric CR was detected during the ANITA-II flight. Here, we report on characteristics of these three unusual CR events, which develop nearly horizontally, 20-30 km above the surface of Earth. In addition, we report on a fourth steeply upward-pointing ANITA-I CR-like radio event which has characteristics consistent with a primary that emerged from the surface of the ice. This suggests a possible τ-lepton decay as the origin of this event, but such an interpretation would require significant suppression of the standard model τ-neutrino cross section

An analysis of a tau-neutrino hypothesis for the near-horizon cosmic-ray-like events observed by ANITA-IV

We present the results of a simulation of the acceptance of the Antarctic Impulsive Transient Antenna (ANITA) to possible υτ point source fluxes detected via τ-lepton-induced air showers. This investigation is framed around the detection of four upward-going extensive air shower events observed very close to the horizon in ANITA-IV. These four events as well as the overall diffuse and point source exposure to Earth-skimming υτ are also compared against published ultrahigh-energy neutrino limits from the Pierre Auger Observatory. We find that while these four events were detected at sky coordinates close to ANITA’s maximum υτ sensitivity and were not simultaneously visible by Auger, the implied fluence necessary for ANITA to observe these events is in tension with limits set by Auger across a wide range of energies and is additionally in tension with ANITA’s Askaryan in-ice neutrino channel above 1019 eV

Analysis of a tau neutrino origin for the near-horizon air shower events observed by the fourth flight of the Antarctic Impulsive Transient Antenna

We study in detail the sensitivity of the Antarctic Impulsive Transient Antenna (ANITA) to possible Formula Presented point source fluxes detected via Formula Presented-lepton-induced air showers. This investigation is framed around the observation of four upward-going extensive air shower events very close to the horizon seen in ANITA-IV. We find that these four upgoing events are not observationally inconsistent with Formula Presented-induced EASs from Earth-skimming Formula Presented both in their spectral properties as well as in their observed locations on the sky. These four events as well as the overall diffuse and point source exposure to Earth-skimming Formula Presented are also compared against published ultrahigh-energy neutrino limits from the Pierre Auger Observatory. While none of these four events occurred at sky locations simultaneously visible by Auger, the implied fluence necessary for ANITA to observe these events is in strong tension with limits set by Auger across a wide range of energies and is additionally in tension with ANITA’s Askaryan in-ice neutrino channel above Formula Presented. We conclude by discussing some of the technical challenges with simulating and analyzing these near horizon events and the potential for future observatories to observe similar events

Upward-pointing cosmic-ray-like events observed with ANITA

These proceedings address a recent publication by the ANITA collaboration of four upward-pointing cosmic-ray-like events observed in the first flight of ANITA. Three of these events were consistent with stratospheric cosmic-ray air showers where the axis of propagation does not intersect the surface of the Earth. The fourth event was consistent with a primary particle that emerges from the surface of the ice suggesting a possible τ-lepton decay as the origin of this event. These proceedings follow-up on the modeling and testing of the hypothesis that this event was of τ neutrino origin

Accelerator Measurements of Magnetically Induced Radio Emission from Particle Cascades with Applications to Cosmic-Ray Air Showers

For 50 years, cosmic-ray air showers have been detected by their radio emission. We present the first laboratory measurements that validate electrodynamics simulations used in air shower modeling. An experiment at SLAC provides a beam test of radio-frequency (rf) radiation from charged particle cascades in the presence of a magnetic field, a model system of a cosmic-ray air shower. This experiment provides a suite of controlled laboratory measurements to compare to particle-level simulations of rf emission, which are relied upon in ultrahigh-energy cosmic-ray air shower detection. We compare simulations to data for intensity, linearity with magnetic field, angular distribution, polarization, and spectral content. In particular, we confirm modern predictions that the magnetically induced emission in a dielectric forms a cone that peaks at the Cherenkov angle and show that the simulations reproduce the data within systematic uncertainties

Antarctic surface reflectivity calculations and measurements from the ANITA-4 and HiCal-2 experiments

The balloon-borne HiCal radio-frequency (RF) transmitter, in concert with the ANITA radio-frequency receiver array, is designed to measure the Antarctic surface reflectivity in the RF wavelength regime. The amplitude of surface-reflected transmissions from HiCal, registered as triggered events by ANITA, can be compared with the direct transmissions preceding them by O ( 10 ) microseconds, to infer the surface power reflection coefficient R . The first HiCal mission (HiCal-1, Jan. 2015) yielded a sample of 100 such pairs, resulting in estimates of R at highly glancing angles (i.e., zenith angles approaching 90°), with measured reflectivity for those events which exceeded extant calculations [P. W. Gorham et al., Journal of Astronomical Instrumentation, 1740002 (2017)]. The HiCal-2 experiment, flying from December 2016–January 2017, provided an improvement by nearly 2 orders of magnitude in our event statistics, allowing a considerably more precise mapping of the reflectivity over a wider range of incidence angles. We find general agreement between the HiCal-2 reflectivity results and those obtained with the earlier HiCal-1 mission, as well as estimates from Solar reflections in the radio-frequency regime [D. Z. Besson et al., Radio Sci. 50, 1 (2015)]. In parallel, our calculations of expected reflectivity have matured; herein, we use a plane-wave expansion to estimate the reflectivity R from both a flat, smooth surface (and, in so doing, recover the Fresnel reflectivity equations) and also a curved surface. Multiplying our flat-smooth reflectivity by improved Earth curvature and surface roughness corrections now provides significantly better agreement between theory and the HiCal-2 measurements

Dynamic tunable notch filters for the Antarctic Impulsive Transient Antenna (ANITA)

The Antarctic Impulsive Transient Antenna (ANITA) is a NASA longduration balloon experiment with the primary goal of detecting ultra-highenergy (> 1018 eV) neutrinos via the Askaryan Effect. The fourth ANITA mission, ANITA-IV, recently flew from Dec 2 to Dec 29, 2016. For the first time, the Tunable Universal Filter Frontend (TUFF) boards were deployed for mitigation of narrow-band, anthropogenic noise with tunable, switchable notch filters. The TUFF boards also performed second-stage amplification by approximately 45 dB to boost the ∼ µV-level radio frequency (RF) signals to ∼ mV-level for digitization, and supplied power via bias tees to the first-stage, antenna-mounted amplifiers. The other major change in signal processing in ANITA-IV is the resurrection of the 90◦ hybrids deployed previously in ANITA-I, in the trigger system, although in this paper we focus on the TUFF boards. During the ANITA-IV mission, the TUFF boards were successfully operated throughout the flight. They contributed to a factor of 2.8 higher total instrument livetime on average in ANITA-IV compared to ANITAIII due to reduction of narrow-band, anthropogenic noise before a trigger decision is made