The plant immune system is activated by microbial patterns that are detected as nonself molecules. Such patterns are recognized by immune receptors that are cytoplasmic or localized at the plasma ...membrane. Cell surface receptors are represented by receptor-like kinases (RLKs) that frequently contain extracellular leucine-rich repeats and an intracellular kinase domain for activation of downstream signaling, as well as receptor-like proteins (RLPs) that lack this signaling domain. It is therefore hypothesized that RLKs are required for RLPs to activate downstream signaling. The RLPs Cf-4 and Ve1 of tomato (Solanum lycopersicum) mediate resistance to the fungal pathogens Cladosporium fulvum and Verticillium dahliae , respectively. Despite their importance, the mechanism by which these immune receptors mediate downstream signaling upon recognition of their matching ligand, Avr4 and Ave1, remained enigmatic. Here we show that the tomato ortholog of the Arabidopsis thaliana RLK Suppressor Of BIR1-1/Evershed (SOBIR1/EVR) and its close homolog S. lycopersicum (Sl)SOBIR1-like interact in planta with both Cf-4 and Ve1 and are required for the Cf-4– and Ve1-mediated hypersensitive response and immunity. Tomato SOBIR1/EVR interacts with most of the tested RLPs, but not with the RLKs FLS2, SERK1, SERK3a, BAK1, and CLV1. SOBIR1/EVR is required for stability of the Cf-4 and Ve1 receptors, supporting our observation that these RLPs are present in a complex with SOBIR1/EVR in planta . We show that SOBIR1/EVR is essential for RLP-mediated immunity and propose that the protein functions as a regulatory RLK of this type of cell-surface receptors.
Recent studies have demonstrated an association between high blood eosinophil counts and greater risk of asthma exacerbations. We sought to determine whether patients hospitalized for an asthma ...exacerbation were at greater risk of readmission if they had a high blood eosinophil count documented before the first hospitalization.
This historical cohort study drew on 2 years of medical record data (Clinical Practice Research Datalink with Hospital Episode Statistics linkage) of patients (aged ≥5 years) admitted to hospital in England for asthma, with recorded blood eosinophil count within 1 baseline year before admission. We analyzed the association between high blood eosinophil count (≥0.35x109 cells/L) and readmission risk during 1 year of follow-up after hospital discharge, with adjustment for predefined, relevant confounders using forward selection.
We identified 2,613 eligible patients with asthma-related admission, of median age 51 years (interquartile range, 36-69) and 76% women (1,997/2,613). Overall, 835/2,613 (32.0%) had a preadmission high blood eosinophil count. During the follow-up year, 130/2,613 patients (5.0%) were readmitted for asthma, including 55/835 (6.6%) with vs. 75/1,778 (4.2%) without high blood eosinophil count at baseline (adjusted hazard ratio HR 1.49; 95% CI 1.04-2.13, p = 0.029). The association was strongest in never-smokers (n = 1,296; HR 2.16, 95% CI 1.27-3.68, p = 0.005) and absent in current smokers (n = 547; HR 1.00, 95% CI 0.49-2.04, p = 0.997).
A high blood eosinophil count in the year before an asthma-related hospitalization is associated with increased risk of readmission within the following year. These findings suggest that patients with asthma and preadmission high blood eosinophil count require careful follow-up, with treatment optimization, after discharge.
ABSTRACT
We present results from six epochs of quasi-simultaneous radio, (sub-)millimetre, infrared, optical, and X-ray observations of the black hole X-ray binary MAXI J1535−571. These observations ...show that as the source transitioned through the hard–intermediate X-ray state towards the soft–intermediate X-ray state, the jet underwent dramatic and rapid changes. We observed the frequency of the jet spectral break, which corresponds to the most compact region in the jet where particle acceleration begins (higher frequencies indicate closer to the black hole), evolves from the infrared band into the radio band (decreasing by ≈3 orders of magnitude) in less than a day. During one observational epoch, we found evidence of the jet spectral break evolving in frequency through the radio band. Estimating the magnetic field and size of the particle acceleration region shows that the rapid fading of the high-energy jet emission was not consistent with radiative cooling; instead, the particle acceleration region seems to be moving away from the black hole on approximately dynamical time-scales. This result suggests that the compact jet quenching is not caused by local changes to the particle acceleration, rather we are observing the acceleration region of the jet travelling away from the black hole with the jet flow. Spectral analysis of the X-ray emission shows a gradual softening in the few days before the dramatic jet changes, followed by a more rapid softening ∼1–2 d after the onset of the jet quenching.
By comparison of the methane mixing ratio and the carbon isotope ratio (δ13CCH4) in Arctic air with regional background, the incremental input of CH4 in an air parcel and the source δ13CCH4 signature ...can be determined. Using this technique the bulk Arctic CH4 source signature of air arriving at Spitsbergen in late summer 2008 and 2009 was found to be −68‰, indicative of the dominance of a biogenic CH4 source. This is close to the source signature of CH4 emissions from boreal wetlands. In spring, when wetland was frozen, the CH4 source signature was more enriched in 13C at −53 ± 6‰ with air mass back trajectories indicating a large influence from gas field emissions in the Ob River region. Emissions of CH4 to the water column from the seabed on the Spitsbergen continental slope are occurring but none has yet been detected reaching the atmosphere. The measurements illustrate the significance of wetland emissions. Potentially, these may respond quickly and powerfully to meteorological variations and to sustained climate warming.
Key Points
Isotopic measurements have been used to identify major sources of Arctic methane
In late summer biogenic methane sources dominate the bulk Arctic source mix
Seabed emissions near Spitsbergen have not been detected reaching the atmosphere
The prevention of bleeding with adequately sustained levels of clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important ...goal in the treatment of hemophilia.
We infused a single-stranded adeno-associated viral (AAV) vector consisting of a bioengineered capsid, liver-specific promoter and factor IX Padua (factor IX-R338L) transgene at a dose of 5×10
vector genomes per kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value. Laboratory values, bleeding frequency, and consumption of factor IX concentrate were prospectively evaluated after vector infusion and were compared with baseline values.
No serious adverse events occurred during or after vector infusion. Vector-derived factor IX coagulant activity was sustained in all the participants, with a mean (±SD) steady-state factor IX coagulant activity of 33.7±18.5% (range, 14 to 81). On cumulative follow-up of 492 weeks among all the participants (range of follow-up in individual participants, 28 to 78 weeks), the annualized bleeding rate was significantly reduced (mean rate, 11.1 events per year range, 0 to 48 before vector administration vs. 0.4 events per year range, 0 to 4 after administration; P=0.02), as was factor use (mean dose, 2908 IU per kilogram range, 0 to 8090 before vector administration vs. 49.3 IU per kilogram range, 0 to 376 after administration; P=0.004). A total of 8 of 10 participants did not use factor, and 9 of 10 did not have bleeds after vector administration. An asymptomatic increase in liver-enzyme levels developed in 2 participants and resolved with short-term prednisone treatment. One participant, who had substantial, advanced arthropathy at baseline, administered factor for bleeding but overall used 91% less factor than before vector infusion.
We found sustained therapeutic expression of factor IX coagulant activity after gene transfer in 10 participants with hemophilia who received the same vector dose. Transgene-derived factor IX coagulant activity enabled the termination of baseline prophylaxis and the near elimination of bleeding and factor use. (Funded by Spark Therapeutics and Pfizer; ClinicalTrials.gov number, NCT02484092 .).
We have developed conceptual designs of two petawatt-class pulsed-power accelerators: Z 300 and Z 800. The designs are based on an accelerator architecture that is founded on two concepts: ...single-stage electrical-pulse compression and impedance matching Phys. Rev. ST Accel. Beams 10, 030401 (2007). The prime power source of each machine consists of 90 linear-transformer-driver (LTD) modules. Each module comprises LTD cavities connected electrically in series, each of which is powered by 5-GW LTD bricks connected electrically in parallel. (A brick comprises a single switch and two capacitors in series.) Six water-insulated radial-transmission-line impedance transformers transport the power generated by the modules to a six-level vacuum-insulator stack. The stack serves as the accelerator’s water-vacuum interface. The stack is connected to six conical outer magnetically insulated vacuum transmission lines (MITLs), which are joined in parallel at a 10-cm radius by a triple-post-hole vacuum convolute. The convolute sums the electrical currents at the outputs of the six outer MITLs, and delivers the combined current to a single short inner MITL. The inner MITL transmits the combined current to the accelerator’s physics-package load. Z 300 is 35 m in diameter and stores 48 MJ of electrical energy in its LTD capacitors. The accelerator generates 320 TW of electrical power at the output of the LTD system, and delivers 48 MA in 154 ns to a magnetized-liner inertial-fusion (MagLIF) target Phys. Plasmas 17, 056303 (2010). The peak electrical power at the MagLIF target is 870 TW, which is the highest power throughout the accelerator. Power amplification is accomplished by the centrally located vacuum section, which serves as an intermediate inductive-energy-storage device. The principal goal of Z 300 is to achieve thermonuclear ignition; i.e., a fusion yield that exceeds the energy transmitted by the accelerator to the liner. 2D magnetohydrodynamic (MHD) simulations suggest Z 300 will deliver 4.3 MJ to the liner, and achieve a yield on the order of 18 MJ. Z 800 is 52 m in diameter and stores 130 MJ. This accelerator generates 890 TW at the output of its LTD system, and delivers 65 MA in 113 ns to a MagLIF target. The peak electrical power at the MagLIF liner is 2500 TW. The principal goal of Z 800 is to achieve high-yield thermonuclear fusion; i.e., a yield that exceeds the energy initially stored by the accelerator’s capacitors. 2D MHD simulations suggest Z 800 will deliver 8.0 MJ to the liner, and achieve a yield on the order of 440 MJ. Z 300 and Z 800, or variations of these accelerators, will allow the international high-energy-density-physics community to conduct advanced inertial-confinement-fusion, radiation-physics, material-physics, and laboratory-astrophysics experiments over heretofore-inaccessible parameter regimes.
Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were commissioned by the Department ...of Health (DH) and developed during 1998-2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were published in January 2001.1 These guidelines describe the precautions healthcare workers should take in three areas: standard principles for preventing HCAI, which include hospital environmental hygiene, hand hygiene, the use of personal protective equipment, and the safe use and disposal of sharps; preventing infections associated with the use of short-term indwelling urethral catheters; and preventing infections associated with central venous catheters. The evidence for these guidelines was identified by multiple systematic reviews of experimental and non-experimental research and expert opinion as reflected in systematically identified professional, national and international guidelines, which were formally assessed by a validated appraisal process. In 2003, we developed complementary national guidelines for preventing HCAI in primary and community care on behalf of the National Collaborating Centre for Nursing and Supportive Care (National Institute for Healthand Clinical Excellence).2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective in preventing HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. Consequently, the DH commissioned a review of new evidence published following the last systematic reviews. We have now updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the original epic guidelines published in 2001 remain robust, relevant and appropriate but that adjustments need to be made to some guideline recommendations following a synopsis of the evidence underpinning the guidelines. These updated national guidelines (epic2) provide comprehensive recommendations for preventing HCAI in hospitals and other acute care settings based on the best currently available evidence. Because this is not always the best possible evidence, we have included a suggested agenda for further research in each section of the guidelines. National evidence-based guidelines are broad principles of best practice which need to be integrated into local practice guidelines. To monitor implementation, we have suggested key audit criteria for each section of recommendations. Clinically effective infection prevention and control practice is an essential feature of protecting patients. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of healthcare in NHS hospitals in England can be minimised.
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