The High Resolution Fly’s Eye (HiRes) experiment has measured the flux of ultrahigh energy cosmic rays using the stereoscopic air fluorescence technique. The HiRes experiment consists of two ...detectors that observe cosmic ray showers via the fluorescence light they emit. HiRes data can be analyzed in monocular mode, where each detector is treated separately, or in stereoscopic mode where they are considered together. Using the monocular mode the HiRes collaboration measured the cosmic ray spectrum and made the first observation of the Greisen–Zatsepin–Kuzmin cutoff. In this paper we present the cosmic ray spectrum measured by the stereoscopic technique. Good agreement is found with the monocular spectrum in all details.
Downy mildew (caused by Pseudoperonospora humuli) causes significant losses in hop (Humulus lupulus L.) cone yield and quality, and potential crown death. Breeding for resistance has proved difficult ...presumably because of the highly quantitative nature of genetic control over expression. The objective of this study was to utilize multiple environments to ascertain downy mildew resistance and identify molecular markers linked to resistance. A widely segregating population, ‘Teamaker’ × USDA 21422M was inoculated and evaluated for downy mildew in field studies (Corvallis, OR and Yakima, WA) and a greenhouse study. Next generation sequencing using an Illumina HiSeq 2000 was performed on this population. Resulting reads were imported into UNEAK TASSEL 4.0 pipeline for processing and SNP-calls. Approximately 120,435 unfiltered SNP markers were identified and of these markers, 9081 high quality markers chosen for association analysis. Data analyses for field studies in OR and WA were performed separately using trait values averaged across blocks. Differential trait associated marker sets were identified across each physical environment with partial overlap between field environments. Mixed linear model analyses identified 39 markers (21 from OR, 10 from WA and eight overlapping) associated with response to downy mildew infection (p < 1 × 10⁻⁴). The most significant 17 markers were validated using high-resolution melting curve analysis and the resistant allele identified. Four SNP markers, along with the respective “resistant” alleles, were classified as highly selective for resistance (model adjusted R² = 0.437). Multiplexing studies are underway to develop a simple PCR tool for selecting downy mildew resistance.
Interleukin-25 (IL-25) and group 2 innate lymphoid cells (ILC2s) defend the host against intestinal helminth infection and are associated with inappropriate allergic reactions. IL-33-activated ILC2s ...were previously found to augment protective tissue-specific pancreatic cancer immunity. Here, we showed that intestinal IL-25-activated ILC2s created an innate cancer-permissive microenvironment. Colorectal cancer (CRC) patients with higher tumor
expression had reduced survival and increased IL-25R-expressing tumor-resident ILC2s and myeloid-derived suppressor cells (MDSCs) associated with impaired antitumor responses. Ablation of IL-25 signaling reduced tumors, virtually doubling life expectancy in an
mutation-driven model of spontaneous intestinal tumorigenesis. Mechanistically, IL-25 promoted intratumoral ILC2s, which sustained tumor-infiltrating MDSCs to suppress antitumor immunity. Therapeutic antibody-mediated blockade of IL-25 signaling decreased intratumoral ILC2s, MDSCs, and adenoma/adenocarcinoma while increasing antitumor adaptive T cell and interferon-γ (IFN-γ)-mediated immunity. Thus, the roles of innate epithelium-derived cytokines IL-25 and IL-33 as well as ILC2s in cancer cannot be generalized. The protumoral nature of the IL-25-ILC2 axis in CRC highlights this pathway as a potential therapeutic target against CRC.
EUSO-TA is a ground-based telescope, installed at the Telescope Array (TA) site in Black Rock Mesa, Utah, USA. This is the first detector to successfully use a Fresnel lens based optical system and ...multi-anode photomultipliers (64 channels per tube, 2304 channels encompassing a 10.6° × 10.6° field of view) for detection of Ultra High Energy Cosmic Rays (UHECR). The telescope is located in front of one of the fluorescence detectors of the TA experiment. Since its installation in 2013, the detector has observed several ultra-high energy cosmic ray events and, in addition, meteors. The limiting magnitude of 5.5 on summed frames ( ∼ 3 ms) has been established. Measurements of the UV night sky emission in different conditions and moon phases and positions have been completed. The performed observations serve as a proof of concept for the future application of this detector technology.
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.
Key Points
Downward Terrestrial Gamma‐ray Flashes occur during strong initial breakdown pulses of negative cloud‐to‐ground and cloud lightning
The initial breakdown pulses consist of streamer‐based fast negative breakdown having transient sub‐pulse conducting events or “sparks”
The streamer to leader transition of negative stepping occurs during strong currents in the final stage of initial breakdown pulses
Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with ...learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using
CPBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq
CPBR28. Regional volumes of distribution (V
) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower
CPBR28 V
in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in V
in other ROIs. Hippocampal
CPBR28 V
was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and
CPBR28 V
, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.
The Telescope Array studies the properties of ultra high energy cosmic rays by measuring the extensive air showers which they induce. We do this using a variety of techniques including an array of ...scintillator detectors to sample the footprint of the air shower when it reaches the Earth's surface and telescopes to measure the fluorescence and Čerenkov light of the air shower. From this we determine the energy spectrum and chemical composition of the primary particles. We also search for sources of cosmic rays and anisotropy. We have found evidence of a possible source of ultra high energy cosmic rays in the northern sky. The experiment and its recent measurements are discussed.
Stepped wedge and cluster randomised crossover trials are examples of cluster randomised designs conducted over multiple time periods that are being used with increasing frequency in health research. ...Recent systematic reviews of both of these designs indicate that the within-cluster correlation is typically taken account of in the analysis of data using a random intercept mixed model, implying a constant correlation between any two individuals in the same cluster no matter how far apart in time they are measured: within-period and between-period intra-cluster correlations are assumed to be identical. Recently proposed extensions allow the within- and between-period intra-cluster correlations to differ, although these methods require that all between-period intra-cluster correlations are identical, which may not be appropriate in all situations. Motivated by a proposed intensive care cluster randomised trial, we propose an alternative correlation structure for repeated cross-sectional multiple-period cluster randomised trials in which the between-period intra-cluster correlation is allowed to decay depending on the distance between measurements. We present results for the variance of treatment effect estimators for varying amounts of decay, investigating the consequences of the variation in decay on sample size planning for stepped wedge, cluster crossover and multiple-period parallel-arm cluster randomised trials. We also investigate the impact of assuming constant between-period intra-cluster correlations instead of decaying between-period intra-cluster correlations. Our results indicate that in certain design configurations, including the one corresponding to the proposed trial, a correlation decay can have an important impact on variances of treatment effect estimators, and hence on sample size and power. An R Shiny app allows readers to interactively explore the impact of correlation decay.
Dethinning extensive air shower simulations Stokes, B.T.; Cady, R.; Ivanov, D. ...
Astroparticle physics,
June 2012, 2012-6-00, 20120601, Volume:
35, Issue:
11
Journal Article
Peer reviewed
Open access
► A technique for restoring information lost to thinning in extensive air shower simulations is described. ► Validation of this technique is accomplished by comparison to full, non-thinned ...simulations. ► This technique makes it computationally feasible to do complete simulations of cosmic ray surface array data sets.
We describe a method for restoring information lost during statistical thinning in extensive air shower simulations. By converting weighted particles from thinned simulations to swarms of particles with similar characteristics, we obtain a result that is essentially identical to the thinned shower, and which is very similar to non-thinned simulations of showers. We call this method dethinning. Using non-thinned showers on a large scale is impossible because of unrealistic CPU time requirements, but with thinned showers that have been dethinned, it is possible to carry out large-scale simulation studies of the detector response for ultra-high energy cosmic ray surface arrays. The dethinning method is described in detail and comparisons are presented with parent thinned showers and with non-thinned showers.