We have performed a 2.5-dimensional magnetohydrodynamic simulation that resolves the propagation and dissipation of Alfvén waves in the solar atmosphere. Alfvénic fluctuations are introduced on the ...bottom boundary of the extremely large simulation box that ranges from the photosphere to far above the solar wind acceleration region. Our model is ab initio in the sense that no corona and no wind are assumed initially. The numerical experiment reveals the quasi-steady solution that has the transition from the cool to the hot atmosphere and the emergence of the high speed wind. The global structure of the resulting hot wind solution fairly well agrees with the coronal and the solar wind structure inferred from observations. The purpose of this study is to complement the previous paper by Matsumoto & Suzuki and describe the more detailed results and the analysis method. These results include the dynamics of the transition region and the more precisely measured heating rate in the atmosphere. Particularly, the spatial distribution of the heating rate helps us to interpret the actual heating mechanisms in the numerical simulation. Our estimation method of heating rate turned out to be a good measure for dissipation of Alfvén waves and low beta fast waves.
Essentials
Emicizumab (Emi) affects the APTT‐based assays of factor (F)VIII activity and inhibitor titer.
A mixture of two anti‐Emi monoclonal antibodies (mAb) effectively neutralized the Emi ...activity.
Anti‐Emi mAbs completely eliminated the influence of Emi on FVIII activity and inhibitor titer.
The inclusion of anti‐Emi mAbs in routine FVIII assays would be useful for Emi‐treated patients.
Summary
Background
Emicizumab is an anti‐factor (F)IXa/X bispecific monoclonal antibody (mAb), mimicking the factor (F)VIIIa cofactor activity. Emicizumab does not require activation by thrombin and its shortening effect on the activated partial prothrombin time (APTT) is more pronounced than that of factor (F)VIII. APTT‐based FVIII activity (FVIII:C) and FVIII inhibiter titer measurements are influenced by the presence of emicizumab.
Aim
To establish a reliable APTT‐based assay to measure FVIII in the presence of emicizumab.
Methods
Plasmas from hemophilia A (HA) patients without or with inhibitors were studied using one‐stage FVIII:C and Bethesda inhibitor assays. Two recombinant anti‐idiotype mAbs to emicizumab (anti‐emicizumab mAbs) were prepared, rcAQ8 to anti‐FIXa‐Fab and rcAJ540 to anti‐FX‐Fab.
Results
The combined anti‐idiotype mAbs (2000 nm each) eliminated the effects of emicizumab on APTTs of HA plasmas without or with inhibitor by competitive inhibition of antibody binding to FIX(a)/FX(a). Measurements of FVIII coagulation activity in HA plasmas without inhibitor were overestimated in the presence of emicizumab (1 μm = ~150 μg mL−1) at all reference levels of FVIII. The addition of anti‐emicizumab mAbs to the assay mixtures completely neutralized the emicizumab and facilitated accurate determination of FVIII:C. Anti‐FVIII inhibitor titers were undetectable in the presence of emicizumab in HA plasmas with inhibitor or normal plasmas mixed with anti‐FVIII neutralizing antibodies. These effects of emicizumab were completely counteracted by the addition of the anti‐idiotype mAbs, allowing accurate assessment of inhibitor titers.
Conclusion
The in vitro inclusion of anti‐emicizumab mAbs in the standard one‐stage coagulation assays prevented interference by emicizumab and enabled accurate measurements of FVIII:C and inhibitor titers.
Essentials
The activated partial prothrombin time (aPTT) cannot predict the activity of emicizumab (Emi).
Adjusted clot waveform analyses using a prothrombin time (PT)/aPTT initiator were developed.
...Activity of Emi in the co‐presence of factor VIII or bypassing agents was quantified.
This assay is useful for assessing coagulation potential in Emi‐treated hemophilia A.
Summary
Background
Emicizumab is an anti‐activated factor IX/FX bispecific antibody that mimics activated FVIII cofactor function. Emicizumab does not require activation by thrombin, and its effect on shortening the activated partial thromboplastin time (APTT) is much greater than that of FVIII. Therefore, the APTT has limited utility in hemophilia A (HA) patients treated with emicizumab.
Aim
To evaluate the global coagulation potential of emicizumab.
Methods
Clot waveform analysis (CWA) with prothrombin time (PT)/APTT mixed reagents was used to define hemostatic monitoring protocols in HA patients. A modified parameter, adjusted‐|min1| (Ad|min1|), was developed. Maximum and minimum percentage transmittance were defined as 100% and 0% in the precoagulation and postcoagulation phases, respectively. Ad|min1| was calculated as an index of the maximum velocity of the coagulation process.
Results
Ad|min1| obtained with mixed‐trigger reagent (PT/APTT/buffer, 1 : 15 : 135) in the presence of emicizumab optimally corresponded to the conversion rate estimated in animals; 0.2–0.4 IU dL−1 equivalent FVIII per 1 μg mL−1 emicizumab). Ex vivo addition of emicizumab to HA plasma with or without inhibitors resulted in concentration‐dependent increases in Ad|min1|, with some individual variations. The addition of various concentrations of FVIII to HA plasma mixed with emicizumab resulted in dose‐dependent increases in Ad|min1|. Similarly, mixtures of activated prothrombin complex concentrate and emicizumab added to HA plasma resulted in dose‐dependent increases in Ad|min1|. In contrast, enhanced coagulation potential appeared to be better defined by the clot time than by Ad|min1| in experiments using recombinant activated FVII.
Conclusion
The PT/APTT reagent‐triggered adjusted CWA could provide a useful means of assessing global coagulation potential in emicizumab‐treated HA patients, with enhanced activity neither masking nor being masked by FVIII or bypassing agents.
ABSTRACT
Neutron star mergers produce a substantial amount of fast-moving ejecta, expanding outwardly for years after the merger. The interaction of these ejecta with the surrounding medium may ...produce a weak isotropic radio remnant, detectable in relatively nearby events. We use late-time radio observations of short duration gamma-ray bursts (sGRBs) to constrain this model. Two samples of events were studied: four sGRBs that are possibly in the local (<200 Mpc) Universe were selected to constrain the remnant non-thermal emission from the sub-relativistic ejecta, whereas 17 sGRBs at cosmological distances were used to constrain the presence of a proto-magnetar central engine, possibly re-energizing the merger ejecta. We consider the case of GRB 170817A/GW170817 and find that in this case the early radio emission may be quenched by the jet blast-wave. In all cases, for ejecta mass range of ${M}_{\rm {ej}}\lesssim 10^{-2}\, (5\times 10^{-2})\, \mathrm{M}_\odot$, we can rule out very energetic merger ejecta ${E}_{\rm {ej}}\gtrsim 5\times 10^{52}\, (10^{53})\, \rm erg$, thus excluding the presence of a powerful magnetar as a merger remnant.
ABSTRACT
We predict linear polarization for a radioactively powered kilonova following the merger of a black hole and a neutron star. Specifically, we perform 3D Monte Carlo radiative transfer ...simulations for two different models, both featuring a lanthanide-rich dynamical ejecta component from numerical-relativity simulations while only one including an additional lanthanide-free disc-wind component. We calculate polarization spectra for nine different orientations at 1.5, 2.5, and 3.5 d after the merger and in the $0.1\!-\!2\, \mu$m wavelength range. We find that both models are polarized at a detectable level 1.5 d after the merger while show negligible levels thereafter. The polarization spectra of the two models are significantly different. The model lacking a disc wind shows no polarization in the optical, while a signal increasing at longer wavelengths and reaching $\sim 1\!-\!6{{\ \rm per\ cent}}$ at $2\, \mu$m depending on the orientation. The model with a disc-wind component, instead, features a characteristic ‘double-peak’ polarization spectrum with one peak in the optical and the other in the infrared. Polarimetric observations of future events will shed light on the debated neutron richness of the disc-wind component. The detection of optical polarization would unambiguously reveal the presence of a lanthanide-free disc-wind component, while polarization increasing from zero in the optical to a peak in the infrared would suggest a lanthanide-rich composition for the whole ejecta. Future polarimetric campaigns should prioritize observations in the first ∼48 h and in the $0.5\!-\!2\, \mu$m range, where polarization is strongest, but also explore shorter wavelengths/later times where no signal is expected from the kilonova and the interstellar polarization can be safely estimated.
To understand the nature of the brightest γ-ray binary system LS 5039, hard x-ray data of the object, taken with the Suzaku and NuSTAR observatories in 2007 and 2016, respectively, were analyzed. The ...two data sets jointly gave tentative evidence for a hard x-ray periodicity, with a period of ∼9 s and a period increase rate by ∼3×10−10 s s−1. Therefore, the compact object in LS 5039 is inferred to be a rotating neutron star, rather than a black hole. Furthermore, several lines of arguments suggest that this object has a magnetic field of several times ∼1010 T, two orders of magnitude higher than those of typical neutron stars. The object is hence suggested to be a magnetar, which would be the first to be found in a binary. The results also suggest that the highly efficient particle acceleration process, known to be operating in LS 5039, emerges through interactions between dense stellar winds from the massive primary star, and ultrastrong magnetic fields of the magnetar.
Atomic-resolution electron microscopes utilize high-power magnetic lenses to produce magnified images of the atomic details of matter. Doing so involves placing samples inside the magnetic objective ...lens, where magnetic fields of up to a few tesla are always exerted. This can largely alter, or even destroy, the magnetic and physical structures of interest. Here, we describe a newly developed magnetic objective lens system that realizes a magnetic field free environment at the sample position. Combined with a higher-order aberration corrector, we achieve direct, atom-resolved imaging with sub-Å spatial resolution with a residual magnetic field of less than 0.2 mT at the sample position. This capability enables direct atom-resolved imaging of magnetic materials such as silicon steels. Removing the need to subject samples to high magnetic field environments enables a new stage in atomic resolution electron microscopy that realizes direct, atomic-level observation of samples without unwanted high magnetic field effects.
Summary Objective This study aimed to investigate alignment based on age in normal knees and alignment based on deformity in osteoarthritis (OA) knees using detailed radiographic parameters. Design ...Various parameters were measured from weight-bearing long leg radiographs of 1251 legs (797 normal and 454 OA knees) as a cross-sectional study. Normal knees were classified by age (young, middle aged, aged, and elderly) and symptomatic OA knees on the basis of the alignment (femorotibial angle (FTA): mild, moderate, severe and profound). The mean measurements in each group were calculated and compared within each group. Results The femoral shaft showed medially bowed curvature ( femoral bowing ) of approximately 2° in the young normal group, which shifted to lateral bowing with age. However, OA knees showed larger lateral bowing with OA grade, which might reduce the condylar-shaft angle and subsequently shifted the mechanical axis medially. Progression of mild to moderate OA might be associated with a decreasing condylar-shaft angle ( femoral condylar orientation ) and widening condylar-plateau angle ( joint space narrowing ) rather than decreasing tibial plateau flattering. Steeping of the tibial plateau inclination due to increasing tibial plateau shift ( tibial plateau compression ) rather than medial tibial bowing might be the main contributor to worsening of varus deformity in knees with severe and profound OA. Conclusions This cross-sectional study might provide the possibility of OA initiation and progression. The lateral curvature of the femoral shaft associated with aging may contribute to the initiation of varus-type OA of the knee. These changes in the femur may be followed by secondary signs of OA progression including varus femoral condylar orientation, medial joint space narrowing, and tibial plateau compression.
We reanalyze the Imaging Photopolarimeter data from Pioneer 10 to study the zodiacal light in the B and R bands beyond Earth orbit, applying an improved method to subtract integrated star light (ISL) ...and diffuse Galactic light (DGL). We found that there exists a significant instrumental offset, making it difficult to examine the absolute sky brightness. Instead, we analyzed the differential brightness, i.e., the difference in sky brightness from the average at high ecliptic latitude, and compared with that expected from the model zodiacal light. At a heliocentric distance of r < 2 au, we found a fairly good correlation between the J-band model zodiacal light and the residual sky brightness after subtracting the ISL and DGL. The reflectances of the interplanetary dust derived from the correlation study are marginally consistent with previous works. The zodiacal light is not significantly detectable at r > 3 au, as previously reported. However, a clear discrepancy from the model is found at r = 2.94 au which indicates the existence of a local dust cloud produced by the collision of asteroids or dust trail from active asteroids (or main-belt comets). Our result confirms that the main component of the zodiacal light (smooth cloud) is consistent with the model even beyond the earth orbit, which justifies the detection of the extragalactic background light after subtracting the zodiacal light based on the model.
Summary
We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts ...during 5.5 months of spaceflight.
Introduction
This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight.
Methods
We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism.
Results
In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium.
Conclusions
The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.
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