A record fuel hot-spot pressure P_{hs}=56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the ...60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition A. Bose et al., Phys. Rev. E 93, 011201(R) (2016), similar to indirect-drive implosions R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015), and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.
Abstract
We search Dark Energy Survey (DES) Year 3 imaging data for galaxy–galaxy strong gravitational lenses using convolutional neural networks. We generate 250 000 simulated lenses at redshifts > ...0.8 from which we create a data set for training the neural networks with realistic seeing, sky and shot noise. Using the simulations as a guide, we build a catalogue of 1.1 million DES sources with 1.8 < g − i < 5, 0.6 < g − r < 3, r_mag > 19, g_mag > 20, and i_mag > 18.2. We train two ensembles of neural networks on training sets consisting of simulated lenses, simulated non-lenses, and real sources. We use the neural networks to score images of each of the sources in our catalogue with a value from 0 to 1, and select those with scores greater than a chosen threshold for visual inspection, resulting in a candidate set of 7301 galaxies. During visual inspection, we rate 84 as ‘probably’ or ‘definitely’ lenses. Four of these are previously known lenses or lens candidates. We inspect a further 9428 candidates with a different score threshold, and identify four new candidates. We present 84 new strong lens candidates, selected after a few hours of visual inspection by astronomers. This catalogue contains a comparable number of high-redshift lenses to that predicted by simulations. Based on simulations, we estimate our sample to contain most discoverable lenses in this imaging and at this redshift range.
Fibrillar protein deposits (amyloid) in the pancreatic islets of Langerhans are thought to be involved in death of the insulin-producing islet β cells in type 2 diabetes mellitus. It has been ...suggested that the mechanism of this β cell death involves membrane disruption by human islet amyloid polypeptide (hIAPP), the major constituent of islet amyloid. However, the molecular mechanism of hIAPP-induced membrane disruption is not known. Here, we propose a hypothesis that growth of hIAPP fibrils at the membrane causes membrane damage. We studied the kinetics of hIAPP-induced membrane damage in relation to hIAPP fibril growth and found that the kinetic profile of hIAPP-induced membrane damage is characterized by a lag phase and a sigmoidal transition, which matches the kinetic profile of hIAPP fibril growth. The observation that seeding accelerates membrane damage supports the hypothesis. In addition, variables that are well known to affect hIAPP fibril formation, i.e., the presence of a fibril formation inhibitor, hIAPP concentration, and lipid composition, were found to have the same effect on hIAPP-induced membrane damage. Furthermore, electron microscopy analysis showed that hIAPP fibrils line the surface of distorted phospholipid vesicles, in agreement with the notion that hIAPP fibril growth at the membrane and membrane damage are physically connected. Together, these observations point toward a mechanism in which growth of hIAPP fibrils, rather than a particular hIAPP species, is responsible for the observed membrane damage. This hypothesis provides an additional mechanism next to the previously proposed role of oligomers as the main cytotoxic species of amyloidogenic proteins.
Abstract Background The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations. ...Objectives This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI. Methods The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding. Results Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21). Conclusions Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study The DAPT Study; NCT00977938 )
We present new radio continuum observations of NGC 253 from the Murchison Widefield Array at frequencies between 76 and 227 MHz. We model the broadband radio spectral energy distribution for the ...total flux density of NGC 253 between 76 MHz and 11 GHz. The spectrum is best described as a sum of a central starburst and extended emission. The central component, corresponding to the inner 500 pc of the starburst region of the galaxy, is best modeled as an internally free-free absorbed synchrotron plasma, with a turnover frequency around 230 MHz. The extended emission component of the spectrum of NGC 253 is best described as a synchrotron emission flattening at low radio frequencies. We find that 34% of the extended emission (outside the central starburst region) at 1 GHz becomes partially absorbed at low radio frequencies. Most of this flattening occurs in the western region of the southeast halo, and may be indicative of synchrotron self-absorption of shock-reaccelerated electrons or an intrinsic low-energy cutoff of the electron distribution. Furthermore, we detect the large-scale synchrotron radio halo of NGC 253 in our radio images. At 154-231 MHz the halo displays the well known X-shaped/horn-like structure, and extends out to ∼8 kpc in the z-direction (from the major axis).
Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI ...in a high malaria transmission area in rural Burkina Faso.
In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens.
A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases.
Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.
Experiments that pursue detection of signals from the Epoch of Reionization (EoR) are relying on spectral smoothness of source spectra at low frequencies. This article empirically explores the effect ...of foreground spectra on EoR experiments by measuring high-resolution full-polarization spectra for the 586 brightest unresolved sources in one of the Murchison Widefield Array (MWA) EoR fields using 45 h of observation. A novel peeling scheme is used to subtract 2500 sources from the visibilities with ionospheric and beam corrections, resulting in the deepest, confusion-limited MWA image so far. The resulting spectra are found to be affected by instrumental effects, which limit the constraints that can be set on source-intrinsic spectral structure. The sensitivity and power-spectrum of the spectra are analysed, and it is found that the spectra of residuals are dominated by point spread function sidelobes from nearby undeconvolved sources. We release a catalogue describing the spectral parameters for each measured source.
Studies on a dose-response relation often report separate relative risks for several risk classes compared with a referent class. When performing a meta-analysis of such studies, one has to convert ...these relative risks into an overall relative risk for a continuous effect. Apart from taking the dependence between separate relative risks into account, this implies assigning an exposure level to each risk factor class and allowing for the nonlinearity of the dose-response relation. The authors describe a relatively simple method solving these problems. As an illustration, they applied this method in a meta-analysis of the association between body mass index and diabetes type 2, restricted to results of follow-up studies (n = 31). Results were compared with a more ad hoc method of assigning exposure levels and with a method in which the nonlinearity of the dose-response method was not taken into account. Differences with the ad hoc method were larger in studies with fewer categories. Not incorporating the nonlinearity of the dose response leads to an overestimation of the pooled relative risk, but this bias is relatively small.
Melanoma cells are relatively resistant to Apo2L/TRAIL (TNF-related apoptosis-inducing ligand). We postulated that resistance might result from higher expression of inhibitors of apoptosis including ...Bcl-2, FLIP (FLICE-like inhibitory protein) or IAPs such as XIAP (X-linked inhibitor of apoptosis) or survivin. Compared to scrambled or mismatch controls, targeting individual inhibitors with siRNA (si-Bcl-2, si-XIAP, si-FLIP or si-Surv), followed by Apo2L/TRAIL resulted in marked increase in apoptosis in melanoma cells. Compared to Bcl-2 or FLIP, siRNAs against XIAP and survivin were most potent in sensitizing melanoma cells. A similar substantial increase in apoptosis was seen in renal carcinoma cells (SKRC-45, Caki-2), following the inhibition of either XIAP or survivin by siRNAs. Apo2L/TRAIL treatment in IAP-targeted cells resulted in cleavage of Bid, activation of caspase-9 and cleavage of PARP (poly ADP-ribose polymerase). Thus, Apo2L/TRAIL resistance can be overcome by interfering with expression of inhibitors of apoptosis regulating both extrinsic (death receptor) or intrinsic (mitochondrial) pathways of apoptosis in melanoma cells.
ABSTRACT
In this work we report the discovery and analysis of three new triply eclipsing triple star systems found with the TESS mission during its observations of the northern skies: TICs 193993801, ...388459317, and 52041148. We utilized the TESS precision photometry of the binary eclipses and third-body eclipsing events, ground-based archival and follow-up photometric data, eclipse timing variations, archival spectral energy distributions, as well as theoretical evolution tracks in a joint photodynamical analysis to deduce the system masses and orbital parameters of both the inner and outer orbits. In one case (TIC 193993801) we also obtained radial velocity measurements of all three stars. This enabled us to ‘calibrate’ our analysis approach with and without ‘truth’ (i.e. RV) data. We find that the masses are good to 1–3 per cent accuracy with RV data and 3–10 per cent without the use of RV data. In all three systems we were able to find the outer orbital period before doing any detailed analysis by searching for a longer-term periodicity in the ASAS-SN archival photometry data – just a few thousand ASAS-SN points enabled us to find the outer periods of 49.28 d, 89.86 d, and 177.0 d, respectively. From our full photodynamical analysis we find that all three systems are coplanar to within 1°−3°. The outer eccentricities of the three systems are 0.003, 0.10, and 0.62, respectively (i.e. spanning a factor of 200). The masses of the three stars {Aa, Ab, and B} in the three systems are: {1.31, 1.19, 1.34}, {1.82, 1.73, 2.19}, and {1.62, 1.48, 2.74} M⊙, respectively.
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