We use the Low Frequency Array (LOFAR) to probe the dynamics of the stepping process of negatively charged plasma channels (negative leaders) in a lightning discharge. We observe that at each step of ...a leader, multiple pulses of vhf (30-80 MHz) radiation are emitted in short-duration bursts (<10 μs). This is evidence for streamer formation during corona flashes that occur with each leader step, which has not been observed before in natural lightning and it could help explain x-ray emission from lightning leaders, as x rays from laboratory leaders tend to be associated with corona flashes. Surprisingly, we find that the stepping length is very similar to what was observed near the ground, however with a stepping time that is considerably larger, which as yet is not understood. These results will help to improve lightning propagation models, and eventually lightning protection models.
We report here on a novel analysis of the complete set of four Stokes parameters that uniquely determine the linear and/or circular polarization of the radio signal for an extensive air shower. The ...observed dependency of the circular polarization on azimuth angle and distance to the shower axis is a clear signature of the interfering contributions from two different radiation mechanisms, a main contribution due to a geomagnetically-induced transverse current and a secondary component due to the build-up of excess charge at the shower front. The data, as measured at LOFAR, agree very well with a calculation from first principles. This opens the possibility to use circular polarization as an investigative tool in the analysis of air shower structure, such as for the determination of atmospheric electric fields.
The radio intensity and polarization footprint of a cosmic-ray induced extensive air shower is determined by the time-dependent structure of the current distribution residing in the plasma cloud at ...the shower front. In turn, the time dependence of the integrated charge-current distribution in the plasma cloud, the longitudinal shower structure, is determined by interesting physics which one would like to extract, such as the location and multiplicity of the primary cosmic-ray collision or the values of electric fields in the atmosphere during thunderstorms. To extract the structure of a shower from its footprint requires solving a complicated inverse problem. For this purpose we have developed a code that semianalytically calculates the radio footprint of an extensive air shower given an arbitrary longitudinal structure. This code can be used in an optimization procedure to extract the optimal longitudinal shower structure given a radio footprint. On the basis of air-shower universality we propose a simple parametrization of the structure of the plasma cloud. This parametrization is based on the results of Monte Carlo shower simulations. Deriving the parametrization also teaches which aspects of the plasma cloud are important for understanding the features seen in the radio-emission footprint. The calculated radio footprints are compared with microscopic CoREAS simulations.
Abstract
The common phenomenon of lightning still harbors many secrets such as what are the conditions for lightning initiation and what is driving the discharge to propagate over several tens of ...kilometers through the atmosphere forming conducting ionized channels called leaders. Since lightning is an electric discharge phenomenon, there are positively and negatively charged leaders. In this work we report on measurements made with the LOFAR radio telescope, an instrument primarily build for radio-astronomy observations. It is observed that a negative leader rather suddenly changes, for a few milliseconds, into a mode where it radiates 100 times more VHF power than typical negative leaders after which it spawns a large number of more typical negative leaders. This mode occurs during the initial stage, soon after initiation, of all lightning flashes we have mapped (about 25). For some flashes this mode occurs also well after initiation and we show one case where it is triggered twice, some 100 ms apart. We postulate that this is indicative of a small (order of 5 km
$$^2$$
2
) high charge pocket. Lightning thus appears to be initiated exclusively in the vicinity of such a small but dense charge pocket.
Alterations in cytosine-5 DNA methylation are frequently observed in most types of human cancer. Although assays utilizing PCR amplification of bisulfite-converted DNA are widely employed to analyze ...these DNA methylation alterations, they are generally limited in throughput capacity, detection sensitivity, and or resolution. Digital PCR, in which a DNA sample is analyzed in distributive fashion over multiple reaction chambers, allows for enumeration of discrete template DNA molecules, as well as sequestration of non-specific primer annealing templates into negative chambers, thereby increasing the signal-to-noise ratio in positive chambers. Here, we have applied digital PCR technology to bisulfite-converted DNA for single-molecule high-resolution DNA methylation analysis and for increased sensitivity DNA methylation detection. We developed digital bisulfite genomic DNA sequencing to efficiently determine single-basepair DNA methylation patterns on single-molecule DNA templates without an interim cloning step. We also developed digital MethyLight, which surpasses traditional MethyLight in detection sensitivity and quantitative accuracy for low quantities of DNA. Using digital MethyLight, we identified single-molecule, cancer-specific DNA hypermethylation events in the CpG islands of RUNX3, CLDN5 and FOXE1 present in plasma samples from breast cancer patients.
We have re-evaluated empirical expressions for the abundance determination of N, O, Ne, S, Cl, Ar and Fe taking into account the latest atomic data and constructing an appropriate grid of ...photoionization models with state-of-the art model atmospheres. Using these expressions we have derived heavy element abundances in the ~310 emission-line galaxies from the Data Release 3 of the Sloan Digital Sky Survey (SDSS) with an observed Hβ flux F(Hβ) > 10-14 erg s-1 cm-2 and for which the O iii λ4363 emission line was detected at least at a 2σ level, allowing abundance determination by direct methods. The oxygen abundance 12 + log O/H of the SDSS galaxies lies in the range from ~7.1 ($Z_\odot$/30) to ~8.5 (0.7 $Z_\odot$). The SDSS sample is merged with a sample of 109 blue compact dwarf (BCD) galaxies with high quality spectra, which contains extremely low-metallicity objects. We use the merged sample to study the abundance patterns of low-metallicity emission-line galaxies. We find that extremely metal-poor galaxies (12 + log O/H < 7.6, i.e. Z < $Z_\odot$/12) are rare in the SDSS sample. The α element-to-oxygen abundance ratios do not show any significant trends with oxygen abundance, in agreement with previous studies, except for a slight increase of Ne/O with increasing metallicity, which we interpret as due to a moderate depletion of O onto grains in the most metal-rich galaxies. The Fe/O abundance ratio is smaller than the solar value, by up to 1 dex at the high metallicity end. We also find that Fe/O increases with decreasing Hβ equivalent width EW(Hβ). We interpret this as a sign of strong depletion onto dust grains, and gradual destruction of those grains on a time scale of a few Myr. All the galaxies are found to have log N/O > –1.6, implying that they have a different nature than the subsample of high-redshift damped Lyα systems with log N/O of ~–2.3 and that their ages are larger than 100–300 Myr. We confirm the apparent increase in N/O with decreasing EW(Hβ), already shown in previous studies, and explain it as the signature of gradual nitrogen ejection by massive stars from the most recent starburst.
The atmospheric electric fields in thunderclouds have been shown to significantly modify the intensity and polarization patterns of the radio footprint of cosmic-ray-induced extensive air showers. ...Simulations indicated a very nonlinear dependence of the signal strength in the frequency window of 30-80 MHz on the magnitude of the atmospheric electric field. In this work we present an explanation of this dependence based on Monte Carlo simulations, supported by arguments based on electron dynamics in air showers and expressed in terms of a simplified model. We show that by extending the frequency window to lower frequencies, additional sensitivity to the atmospheric electric field is obtained.
We observe a large fraction of circular polarization in radio emission from extensive air showers recorded during thunderstorms, much higher than in the emission from air showers measured during ...fair-weather circumstances. We show that the circular polarization of the air showers measured during thunderstorms can be explained by the change in the direction of the transverse current as a function of altitude induced by atmospheric electric fields. Thus by using the full set of Stokes parameters for these events, we obtain a good characterization of the electric fields in thunderclouds. We also measure a large horizontal component of the electric fields in the two events that we have analyzed.
The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was ...to replicate control arms from four non-small cell lung cancer (NSCLC) randomized controlled trials (RCT) to analyze overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) using RWD.
This study used RWD from a nationwide de-identified database and a clinico-genomic database to replicate OS, PFS, and ORR endpoints in the chemotherapy control arms of four first-line NSCLC RCTs evaluating atezolizumab IMpower150-wild-type (WT), IMpower130-WT, IMpower131, and IMpower132. Additional objectives were to develop a definition of real-world PFS (rwPFS) and to evaluate the real-world response rate (rwRR) endpoint.
Baseline demographic and clinical characteristics were balanced after application of propensity score weighting methods. For rwPFS and OS, RWD external controls were generally similar to their RCT control counterparts. Across all four trials, the hazard ratio (HR) point estimates comparing trial controls with external controls were closer to 1.0 for the PFS endpoint than for the OS endpoint. An exploratory assessment of rwRR in RWD revealed a slight but nonsignificant overestimation of RCT ORR, which was unconfounded by baseline characteristics.
RWD can be used to reasonably replicate the OS and PFS of chemotherapy control arms of first-line NSCLC RCTs. Additional studies can provide greater insight into the utility of RWD in drug development.
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