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.
During the past two decades, mindfulness meditation has gone from being a fringe topic of scientific investigation to being an occasional replacement for psychotherapy, tool of corporate well-being, ...widely implemented educational practice, and “key to building more resilient soldiers.” Yet the mindfulness movement and empirical evidence supporting it have not gone without criticism. Misinformation and poor methodology associated with past studies of mindfulness may lead public consumers to be harmed, misled, and disappointed. Addressing such concerns, the present article discusses the difficulties of defining mindfulness, delineates the proper scope of research into mindfulness practices, and explicates crucial methodological issues for interpreting results from investigations of mindfulness. For doing so, the authors draw on their diverse areas of expertise to review the present state of mindfulness research, comprehensively summarizing what we do and do not know, while providing a prescriptive agenda for contemplative science, with a particular focus on assessment, mindfulness training, possible adverse effects, and intersection with brain imaging. Our goals are to inform interested scientists, the news media, and the public, to minimize harm, curb poor research practices, and staunch the flow of misinformation about the benefits, costs, and future prospects of mindfulness meditation.
Glucagon and glucagon-like peptide (GLP)-1 are the primary products of proglucagon processing from the pancreas and gut, respectively. Giving dual agonists with glucagon and GLP-1 activity to ...diabetic, obese mice causes enhanced weight loss and improves glucose tolerance by reduction of food intake and by increase in energy expenditure (EE). We aimed to observe the effect of a combination of glucagon and GLP-1 on resting EE and glycemia in healthy human volunteers. In a randomized, double-blinded crossover study, 10 overweight or obese volunteers without diabetes received placebo infusion, GLP-1 alone, glucagon alone, and GLP-1 plus glucagon simultaneously. Resting EE--measured using indirect calorimetry--was not affected by GLP-1 infusion but rose significantly with glucagon alone and to a similar degree with glucagon and GLP-1 together. Glucagon infusion was accompanied by a rise in plasma glucose levels, but addition of GLP-1 to glucagon rapidly reduced this excursion, due to a synergistic insulinotropic effect. The data indicate that drugs with glucagon and GLP-1 agonist activity may represent a useful treatment for type 2 diabetes and obesity. Long-term studies are required to demonstrate that this combination will reduce weight and improve glycemia in patients.
UPF1-like helicases play roles in telomeric heterochromatin formation and X-chromosome inactivation, and also in monogenic variant surface glycoprotein (VSG) expression via VSG exclusion-factor-2 ...(VEX2), a UPF1-related protein in the African trypanosome. We show that VEX2 associates with chromatin specifically at the single active VSG expression site on chromosome 6, forming an allele-selective connection, via VEX1, to the trans-splicing locus on chromosome 9, physically bridging two chromosomes and the VSG transcription and splicing compartments. We further show that the VEX-complex is multimeric and self-regulates turnover to tightly control its abundance. Using single cell transcriptomics following VEX2-depletion, we observed simultaneous derepression of many other telomeric VSGs and multi-allelic VSG expression in individual cells. Thus, an allele-selective, inter-chromosomal, and self-limiting VEX1-2 bridge supports monogenic VSG expression and multi-allelic VSG exclusion.
The stream of visual information sent from photoreceptors to second-order bipolar cells is intercepted by laterally interacting horizontal cells that generate feedback to optimize and improve the ...efficiency of signal transmission. The mechanisms underlying the regulation of graded photoreceptor synaptic output in this nonspiking network have remained elusive. Here, we analyze with patch clamp recording the novel mechanisms by which horizontal cells control pH in the synaptic cleft to modulate photoreceptor neurotransmitter release. First, we show that mammalian horizontal cells respond to their own GABA release and that the results of this autaptic action affect cone voltage-gated Ca2+ channel (CaV channel) gating through changes in pH. As a proof-of-principle, we demonstrate that chemogenetic manipulation of horizontal cells with exogenous anion channel expression mimics GABA-mediated cone CaV channel inhibition. Activation of these GABA receptor anion channels can depolarize horizontal cells and increase cleft acidity via Na+/H+ exchanger (NHE) proton extrusion, which results in inhibition of cone CaV channels. This action is effectively counteracted when horizontal cells are sufficiently hyperpolarized by increased GABA receptor (GABAR)-mediated HCO3- efflux, alkalinizing the cleft and disinhibiting cone CaV channels. This demonstrates how hybrid actions of GABA operate in parallel to effect voltage-dependent pH changes, a novel mechanism for regulating synaptic output.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We describe Global Atmosphere 4.0 (GA4.0) and Global Land 4.0 (GL4.0): configurations of the Met Office Unified Model and JULES (Joint UK Land Environment Simulator) community land surface model ...developed for use in global and regional climate research and weather prediction activities. GA4.0 and GL4.0 are based on the previous GA3.0 and GL3.0 configurations, with the inclusion of developments made by the Met Office and its collaborators during its annual development cycle. This paper provides a comprehensive technical and scientific description of GA4.0 and GL4.0 as well as details of how these differ from their predecessors. We also present the results of some initial evaluations of their performance. Overall, performance is comparable with that of GA3.0/GL3.0; the updated configurations include improvements to the science of several parametrisation schemes, however, and will form a baseline for further ongoing development.
The first flight of the Antarctic Impulsive Transient Antenna (ANITA) experiment recorded 16 radio signals that were emitted by cosmic-ray induced air showers. The dominant contribution to the ...radiation comes from the deflection of positrons and electrons in the geomagnetic field, which is beamed in the direction of motion of the air shower. For 14 of these events, this radiation is reflected from the ice and subsequently detected by the ANITA experiment at a flight altitude of ∼36 km. In this paper, we estimate the energy of the 14 individual events and find that the mean energy of the cosmic-ray sample is 2.9 × 1018 eV, which is significantly lower than the previous estimate. By simulating the ANITA flight, we calculate its exposure for ultra-high energy cosmic rays. We estimate for the first time the cosmic-ray flux derived only from radio observations and find agreement with measurements performed at other observatories. In addition, we find that the ANITA data set is consistent with Monte Carlo simulations for the total number of observed events and with the properties of those events.
High densities of the corallivorous crown-of-thorns starfish (CoTS;
Acanthaster
sp.) have occurred throughout the Indo-Pacific often resulting in widespread coral loss. Whilst CoTS have previously ...been recorded at Barrow and the Montebello Islands, in the Pilbara offshore bioregion of northwestern Australia, their densities were relatively low. Outbreak densities of CoTS have been described as the level at which the rate of coral consumption by the starfish is equal to or greater than rate at which the coral grows. In 2014, we recorded densities as high as 320 ± 58 CoTS ha
−1
in the region which is well above recognised outbreak densities. Whilst there is little terrestrial runoff and agriculture in the Pilbara region, both temperature and chlorophyll-α levels appear to be sufficient to allow a high degree of CoTS larval success in most years. The region was subjected to anomalously high water temperatures during the summers of 2010–2011 and particularly 2012–2013 which resulted in the mortality of almost 70% of live coral. We hypothesise that the high densities of CoTS observed are a result of CoTS responding to a reduced food supply and aggregating around the remaining live coral resulting in outbreak densities rather than a significant increase in the number of CoTS in the area. The small amount of remaining live coral is concentrated in a few areas and this, combined with high densities of CoTS in these areas, suggest that CoTS represent a significant threat to the recovery of the coral communities of the region.
Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.
The pilot UK Lung Cancer Screening (UKLS) is a randomised ...controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction.
247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569).
The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction.
ISRCTN 78513845.
We present a comprehensive report on the experimental details of the Antarctic Impulsive Transient Antenna (ANITA) long-duration balloon payload, including the design philosophy and realization, ...physics simulations, performance of the instrument during its first Antarctic flight completed in January of 2007, and expectations for the limiting neutrino detection sensitivity.
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