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Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1–3. Recent observations of a Galactic FRB4–8suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (au; Earth–Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10–12show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately 903−111+72parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

Fast radio bursts (FRBs) are millisecond-duration radio transients1,2of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3–5or relativistic shocks far from the central energy source6–8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.

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Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry. Cellular and molecular impacts of altered KLF4 expression and TGF-β signaling were determined using immunofluorescence, western blot, reverse-transcriptase PCR, chromatin immunoprecipitation and promoter reporter assays. Loss of KLF4 expression in primary HCC closely correlated with decreased Smad7 expression, increased p-Smad2/3 expression and independently predicts reduced overall and relapse-free survival after surgery. TGF-β signaling components were expressed in most HCC cells, and activation of TGF-β signaling promoted cell migration and invasion. Enforced KLF4 expression blocked TGF-β signal transduction and inhibited cell migration and invasion via activation of Smad7 transcription, whereas deletion of its C-terminal zinc-finger domain diminished this effect. KLF4 protein physically interacts with the Smad7 promoter. Promoter deletion and point mutation analyses revealed that a region between nucleotides –15 bp and –9 bp of the Smad7 promoter was required for the induction of Smad7 promoter activity by KLF4. Our data indicate that KLF4 suppresses oncogenic TGF-β signaling by activation of Smad7 transcription, and that loss of KLF4 expression in primary HCC may contribute to activation of oncogenic TGF-β signaling and subsequent tumor progression.

miR-374a has been reported to function as an oncogene during tumor pathogenesis. In this study, miR-374a is observed to reduce nasopharyngeal carcinoma (NPC) cell proliferation, migration, invasion, metastasis and cisplatin (DDP) resistance in vitroand in vivo. Mechanistic analyses indicate that miR-374a directly targets CCND1 to inactivate pPI3K/pAKT/c-JUN forming a negative feedback loop, as well as suppressing downstream signals related to cell cycle progression and epithelial−mesenchymal transition (EMT). Interestingly, we also observed that miR-374a direct targeting of CCND1 is modulated by tumor suppressor PDCD4 via suppressing pPI3K/pAKT/c-JUN signaling. In clinical specimens, miR-374a was positively and negatively correlated with expression of PDCD4 and CCND1, respectively. Our studies are the first to demonstrate that the miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop induced by PDCD4 supresses NPC cell growth, metastasis and chemotherapy resistance.

Recent progress in kilojoule-scale high-intensity lasers has opened up new areas of research in radiography, laboratory astrophysics, high-energy-density physics, and fast-ignition (FI) laser fusion. FI requires efficient heating of pre-compressed high-density fuel by an intense relativistic electron beam produced from laser–matter interaction. Understanding the details of electron beam generation and transport is crucial for FI. Here we report on the first visualization of fast electron spatial energy deposition in a laser-compressed cone-in-shell FI target, facilitated by doping the shell with copper and imaging the K-shell radiation. Multi-scale simulations accompanying the experiments clearly show the location of fast electrons and reveal key parameters affecting energy coupling. The approach provides a more direct way to infer energy coupling and guide experimental designs that significantly improve the laser-to-core coupling to 7%. Our findings lay the groundwork for further improving efficiency, with 15% energy coupling predicted in FI experiments using an existing megajoule-scale laser driver.

Sepsis is frequently seen in severely burned patients, however it is not common in those with small-area burns. We present a case of a 22-year-old man suffering from a hot crush injury to his left hand dorsum covering 1% of his total body surface area. The patient developed severe sepsis and superficial vein thrombosis, probably due to wound infection. Culture of the wound secretion indicated Corynebacterium striatum. Following intensive topical and systemic treatment the severe sepsis was controlled. The local wound was repaired by the abdominal skin pedicle flap which had taken well by day 27 post admission. A topical superficial vein thrombosis, unintentionally found 42 days after admission, was partially excised. This case demonstrates that when treating severe sepsis in patients with small-area burns, the timely recognition and diagnosis along with active systemic support, play a vital role in successful management.Declaration of interest:None of the authors have any financial interest to declare.

OBJECTIVES: This study measured the serum concentrations of resistin and adiponectin in Chinese subjects with impaired glucose tolerance (IGT) and investigated their association with insulin resistance, metabolic parameters and circulating inflammatory markers. METHODS: A total of 124 subjects participated in the study (44 with IGT and 80 with normal glucose tolerance [NGT]). Fasting serum concentrations of lipids, glucose, insulin and adipocytokines (resistin, adiponectin, leptin, tumour necrosis factor-α [TNF-α], interleukin-6 and C-reactive protein) were measured. RESULTS: Serum resistin concentrations were similar in the IGT and NGT groups but were significantly higher in overweight/obese IGT subjects than in those of normal weight. Serum adiponectin concentrations were significantly lower in the IGT group than in the NGT group. In the IGT group, resistin was positively correlated with age, body mass index and TNF-α, and adiponectin was correlated positively with high-density lipoprotein cholesterol and negatively with TNF-α and waist/hip ratio. CONCLUSIONS: Circulating resistin is unlikely to be a major mediator of glucose tolerance in humans but it may have an inflammatory role in IGT. The data support the theory that circulating adiponectin has an anti-inflammatory and anti-insulin resistance function.

Rubber suspensions are important components in railway vehicles. The offset sandwich mount is a type of rubber spring used on rail vehicles as the primary suspension above the axlebox on a bogie. In this installation, a pair of mounts is arranged within a vee configuration, such that the movements in all planes are controlled by a combined shear and compression displacement. This article evaluates the important aspects in the rubber suspension design when using a higher order material properties in an extreme large deformation. On one hand, using a higher order of material model has enabled prediction of larger deformations that are required for the actual product in the ultimate loading used in rail dynamic environment. On the other hand, using a higher order of material model with full integration elements, however, may mislead the design concept to an incorrect direction. It is important to note that the accuracy of the stress calculation is not guaranteed by a reasonable load–deflection prediction, even validated against a test result. Three methods to check the reliability of the calculated stresses are proposed. The investigation has been validated against a laboratory test. It is suggested that a higher order of material model should be used with reduced integration elements.

The stress variations which occur in indented pipes, due to internal pressure fluctuations, are investigated using the results of finite element (FE) analyses for two typical pipe steel materials. The insertion, and subsequent withdrawal, of an indenter results in residual stress and indentation. It is found that the stress variations in indented pipes, due to the internal pressure fluctuations, are in the elastic range for practical pressures. Semi-empirical formulations for predicting the stress variations and the indentation depth changes due to internal pressure fluctuations are developed. A very close correlation is obtained between the results obtained from the FE analyses and predictions based on semi-empirical formulations.

This paper focuses on modified projective synchronization of uncertain unified chaotic systems via backstepping approach. A parameter observer is designed to identify the unknown parameter of unified chaotic systems and a novel backstepping control method is presented for synchronizing two identical unified chaotic systems with each other. Numerical simulations are shown to verify the feasibility and effectiveness of the proposed control technique.

The offset sandwich mount design is often considered for application on rail vehicles. This paper reviews several different aspects of the product. These include the more commonly evaluated benefits of higher order material properties, the product design and its associated geometry optimisation. It is shown that a large error occurs when calculating the rubber shrinkage using a constant coefficient in the moulding process. Hence a postulation is made to link the compressibility with temperature change, which leads to the accuracy increased by fivefold against the measurement. A design concept, balancing the internal moments in different layers of the component, is proposed for this type of the product. Finally the paper suggests an effective stress criterion which takes into account all stress components when considering the complications associated with multiaxial loadings. The objective is to identify which can be considered the best approach for crack initiation evaluation.

In this article, a two-degree-of-freedom model for the disc brake system is set up by considering the vertical motion of the brake unit and the pitch motion of the bogie frame, and the sliding friction interface between the brake lining and disc is included in the model. Using the Hurwitz determinants, an algebraic criterion for determining the Hopf bifurcation point of the system is proposed. The vehicle speed at the Hopf bifurcation point is defined as the critical speed where the equilibrium position of the disc brake system loses stability and the limit cycle emerges. In order to investigate the stability of the disc brake system, parametric studies are undertaken. It is shown that the mass of brake unit, vertical damping of primary suspension, friction coefficient, and brake normal force between the lining and disc have significant influences on the critical speed. The instability of the system may not occur if the parameters are properly designed. The limit cycle arisen due to the loss of stability of the equilibrium position is studied using the numerical integration method. It is found that once the brake system loses its stability at a certain speed, the stick—slip motion occurs and the limit cycle oscillation will last until the vehicle comes to a standstill. It is also known that the frequency of limit cycle is significantly affected by the mass and suspended stiffness of the brake unit but is not related to the vehicle speed in the braking process.

AbstractOne suggested approach to decreasing preheat of Laboratory for Laser Energetics cryotargets is to add a silicon dopant ~4 to 6 at.% to normal plasma polymer. As in the case of pure CH and CD shells used previously, the physical properties of these shells are of utmost importance to allow proper fielding for cryogenic shots. We have fabricated and characterized two types of Si-doped glow discharge polymer (GDP) capsules: single-layer Si-doped GDP shells (SiGDP) and double-layer Si-doped GDP/SCD shells (SiGDP/SCD).The Si-doped GDP shells with an ~870-μm diameter and 5-μm-thick walls were fabricated to meet the cryogenic direct laser fusion experiment requirements. Si-doped GDP shells with <0.25-μm wall variation and 5% silicon dopant level were delivered. These cryogenic shells can survive a 1000-atm D2or deuterium-tritium fill and cryogenic cooling without bursting or buckling. With an average buckle strength of 70 psi, a half-life of 12 s, and a D2permeability at 20°C of 2.4 × 10-14(mol × m/m2× Pa × s), Si-doped GDP shells meet the criteria for cryogenic experiments. A possible drawback of the SiGDP layer is its rapid OH pickup due to exposure to air, which can increase the amount of infrared light absorbed in the shell wall as compared to D2ice and possibly result in a poor ice uniformity during the cryogenic layering process. The absorption coefficient of the SiGDP at 3160 cm-1measured by Fourier transform infrared spectroscopy is ~48 cm-1at 0.1 h to ~130 cm-1at 167 h of air exposure.

Traditional Chinese medicine (TCM) is frequently used to treat attention deficit hyperactivity disorders (ADHD) in children in China. However, until now there has been no strong evidence to prove that TCM has better efficacy than western medicine. In this systematic study of 34 studies published in the Chinese literature, the effectiveness of TCM in treating ADHD in children was examined and compared with methylphenidate (MPH), which is widely used to treat ADHD. It was found that TCM may have equal or better effectiveness than MPH. However, the lack of high-quality clinical trials to support this conclusion means that it is not currently possible to recommend any particular kind of TCM preparation for treating ADHD in children.

Thin iron films grown on carbon fibers were prepared by atmospheric pressure (AP), metal‐organic (MO) CVD, which was conducted under pure hydrogen/argon atmospheres. Their crystalline structures and morphologies were characterized by X‐ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The film growth and structure, as a function of the deposition temperature, hydrogen gas flow rate, and precursor sublimation rate, were investigated. It was concluded that the optimum control of the three above mentioned process parameters was important and essential for obtaining high‐quality iron film. Based on these analyses and results, a possible deposition mechanism was proposed.

AbstractPreviously we have developed a production process for both standard density (100 mg/cc) and high-density (180-200 mg/cc) resorcinol formaldehyde (RF) foam shells with a triple orifice droplet generator. These foam shells are needed for direct drive inertial confinement laser fusion experiments on the OMEGA laser facility at the University of Rochester. Although this process has been developed into production mode, the yield of high density RF (HDRF) and standard density (SDRF) shells with acceptable wall uniformity has been poor. This yield depends on the type of RF shell that is being fabricated. For HDRF this yield is ~5% while for the SDRF shells the yield is ~30%. We have made improvements in the yield of these shells that meet the wall uniformity specification by modifying the composition of the outer oil solution (O2) in the microencapsulation emulsion. This improvement was achieved by a small addition (0.60 wt.%) of a styrene-butadiene-styrene (SBS) block copolymer into the outer oil (O2) solution that increased the interfacial tension of the emulsion system as well as the viscosity of the O2 solution. This modification improved the out of round and concentricity of the RF foam shells resulting in an increase in the yield of shells that meet the target wall uniformity specifications.

The diffraction patterns of submicron fluorescent particles were obtained using an air immersion objective (M= 40, NA = 0.6) under non-design optical conditions through a thick cover glass with a mismatched refractive index. The particle diffraction patterns changed with the defocus distance out of the front focal plane in the optical axis direction. A scalar diffraction model was applied to analyze the diffraction patterns for various optical conditions and to determine the defocus distance of the particle according to the measured intensity distribution of the diffraction pattern image. The results showed that the defocus distances have a submicron accuracy (0.2-0.3 µm), which can be used to determine the three-dimensional flow velocity distribution in a micro-channel and to track the three-dimensional Brownian motion of the particles for the specified defocus conditions.

The spherical expanded polystyrene particle–oil two-phase flow in a vertical pipe was used to simulate the dispersed phase distribution in laminar bubbly flows. A three-dimensional particle image tracking technique was used to track the particles in the flow to study the ordered structure of dispersed phase distribution and its transition to disorder. The ordered structures behaved as particle strings aligned in the flow direction as induced by the flow shear. The structures were quite durable in high liquid velocity flows and dispersed gradually as the liquid velocity decreased. In lower velocity flows, the particles tended to form clusters in the horizontal direction, as predicted by potential theory for spherical bubbles rising in a quiescent inviscid liquid and as observed in experiments on non-shear bubbly water flows.

In this paper, a new approach to sensor validation in real time is described that is based on (1) representation of the sensor signal by wavelets, (2) decomposition of the signal for different frequency ranges, (3) formation of a prediction model using information at an appropriate frequency (level of decomposition), (4) calculation of residuals, namely, the difference between the predictions of the prediction model and the values of the signal decomposed at the same frequency, and (5) diagnosis of the existence of faults via tests on the residuals. The proposed strategy is able to eliminate the effect of noise and process changes from the effects of physical changes in the sensor itself. To demonstrate the effectiveness of the proposed strategy, a simulated noisy signal from a thermocouple in a continuous stirred tank reactor and a temperature signal from an operating pilot distillation column were analyzed. The results of the diagnosis indicated that the proposed strategy had a low type I (false alarm) rate and a satisfactory type II (failure to detect faults) rate.

Abstract: A three-dimensional photographic method has been developed to measure phase distributions in bubbly flow in a pipe. In this method a mirror was used to reflect a side view of the flow into the front-view direction, and then flow images in both views were taken simultaneously by one camera. After three-dimensional position and size of each bubble in the flow field were determined by matching the two bubble images in the side and front views, the phase distributions were obtained for the bubbly flow.

Poly(ADP-ribose) polymerase (PARP) knockout mice are resistant to murine models of human diseases such as cerebral and myocardial ischemia, traumatic brain injury, diabetes, Parkinsonism, endotoxic shock and arthritis, implicating PARP in the pathogenesis of these diseases. Potent selective PARP inhibitors are therefore being evaluated as novel therapeutic agents in the treatment of these diseases. Inhibition or depletion of PARP, however, increases genomic instability in cells exposed to genotoxic agents. We recently demonstrated the presence of a genomically unstable tetraploid population in PARP(-/-) fibroblasts and its loss after stable transfection with PARP cDNA. To elucidate whether the genomic instability is attributable to PARP deficiency or lack of PARP activity, we investigated the effects of PARP inhibition on development of tetraploidy. Immortalized wild-type and PARP(-/-) fibroblasts were exposed for 3 weeks to 20 microM GPI 6150 (1,11b-dihydro-[2H:]benzopyrano[4,3,2-de]isoquinolin-3-one), a novel small molecule specific competitive inhibitor of PARP (K(i) = 60 nM) and one of the most potent PARP inhibitors to date (IC(50) = 0.15 microM). Although GPI 6150 initially decreased cell growth in wild-type cells, there was no effect on cell growth or viability after 24 h. GPI 6150 inhibited endogenous PARP activity in wild-type cells by approximately 91%, to about the residual levels in PARP(-/-) cells. Flow cytometric analysis of unsynchronized wild-type cells exposed for 3 weeks to GPI 6150 did not induce the development of tetraploidy, suggesting that, aside from its catalytic function, PARP may play other essential roles in the maintenance of genomic stability.

A number of authors have carried out finite element simulations of the damage produced in fibre composite laminates by medium and high velocity impacts, with results which generally show good agreement with experimental evidence. In some engineering applications, these laminates may be constructed with pre-existing holes or cut-outs whose presence may significantly affect the nature of the impact damage. As far as is known, no study of this problem has appeared in the literature and this paper reports the first results of an experimental and simulation exercise to determine the additional damage arising from the presence of holes. The experimental evidence shows that the holes can induce matrix cracking in the lower lamina which is additional to that arising in the laminate without holes. These matrix cracks can extend from the region directly below the impact to the edge of the holes and in some circumstances further cracks can emanate from the far side of the holes. The simulation predicts that the presence of the holes can give rise to multiple cracks directly below the impact region which spread towards but not up to the holes, together with a crack emanating from the hole towards the impact region. Thus, whilst the computations are in qualitative agreement with the experimental evidence there is a need for further work in order to improve on the predictions.

A general mathematical model for the prediction of pressure, flow rate, and flux profiles in an ultrafiltration/microfiltration hollow fiber membrane module whose shell side is filled with beads has been developed. The model was studied for a variety of operational modes in such modules, e.g., ultrafiltration/microfiltration, permeate flow rate control, Starling flow (encountered in hollow fiber bioreactors), and tube-side elution (encountered in filtration-cum-chromatography processes), etc., with or without a bead-filled extended section at the permeate outlet. An algorithm is provided to determine the model parameters from experimental data using the model equations. The solutions developed have been used to study the uniformity of transmembrane pressure profile along the module length using a quantity called the uniformity factor α. This factor shows that the model can be a useful tool for achieving the desired module performance in a number of quite different applications. The model predicts successfully the nature of the transmembrane pressure profile and the solvent flux profile in situations that are quite different, namely, conventional ultrafiltration and Starling flow. The approach used in this study can also be adopted to develop a model for description of other operational modes such as backflushing and shell-side elution used in the processes of filtration-cum-chromatography. Those applications employing similar device configurations may also use this model to predict the pressure and flux profiles to facilitate the design of the process and the operation conditions.