Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis : a subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.651); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68) and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Spectrum from the warped compactifications with the de Sitter universe

We discuss the spectrum of the tensor metric perturbations and the stability of warped compactifications with the de Sitter spacetime in the higher-dimensional gravity. The spacetime structure is given in terms of the warped product of the non-compact direction, the spherical internal dimensions and the four-dimensional de Sitter spacetime. To realize a finite bulk volume, we construct the brane world model, using the cut-copy-paste method. Then, we compactify the spherical directions on the brane. In any case, we show the existence of the massless zero mode and the mass gap of it with massive Kaluza-Klein modes. Although the brane involves the spherical dimensions, no light massive mode is excited. We also investigate the scalar perturbations, and show that the model is unstable due to the existence of a tachyonic bound state, which seems to have the universal negative mass square, irrespective of the number of spacetime dimensions.Comment: Journal version (JHEP

Measurement of stratospheric and mesospheric winds with a submillimeter wave limb sounder: results from JEM/SMILES and simulation study for SMILES-2

Satellite missions for measuring winds in the troposphere and thermosphere will be launched in a near future. There is no plan to observe winds in the altitude range between 30-90 km, though middle atmospheric winds are recognized as an essential parameter in various atmospheric research areas. Sub-millimetre limb sounders have the capability to fill this altitude gap. In this paper, we summarize the wind retrievals obtained from the Japanese Superconducting Submillimeter Wave Limb Emission Sounder (SMILES) which operated from the International Space Station between September 2009 and April 2010. The results illustrate the potential of such instruments to measure winds. They also show the need of improving the wind representation in the models in the Tropics, and globally in the mesosphere. A wind measurement sensitivity study has been conducted for its successor, SMILES-2, which is being studied in Japan. If it is realized, sub-millimeter and terahertz molecular lines suitable to determine line-of-sight winds will be measured. It is shown that with the current instrument definition, line-of-sight winds can be observed from 20 km up to more than 160 km. Winds can be retrieved with a precision better than 5 m s(-1) and a vertical resolution of 2-3 km between 35-90 km. Above 90 km, the precision is better than 10 m s(-1) with a vertical resolution of 3-5 km. Measurements can be performed day and night with a similar sensitivity. Requirements on observation parameters such as the antenna size, the satellite altitude are discussed. An alternative setting for the spectral bands is examined. The new setting is compatible with the general scientific objectives of the mission and the instrument design. It allows to improve the wind measurement sensitivity between 35 to 90 km by a factor 2. It is also shown that retrievals can be performed with a vertical resolution of 1 km and a precision of 5-10 m s(-1) between 50 and 90 km. RAGAM A, 1953, PHYSICAL REVIEW, V92, P144

Gyrofluid simulations of collisionless reconnection in the presence of diamagnetic effects

The effects of the ion Larmor radius on magnetic reconnection are investigated by means of numerical simulations, with a Hamiltonian gyrofluid model. In the linear regime, it is found that ion diamagnetic effects decrease the growth rate of the dominant mode. Increasing ion temperature tends to make the magnetic islands propagate in the ion diamagnetic drift direction. In the nonlinear regime, diamagnetic effects reduce the final width of the island. Unlike the electron density, the guiding center density does not tend to distribute along separatrices and at high ion temperature, the electrostatic potential exhibits the superposition of a small scale structure, related to the electron density, and a large scale structure, related to the ion guiding-center density

Gyrofluid simulations of collisionless reconnection in the presence of diamagnetic effects

The effects of the ion Larmor radius on magnetic reconnection are investigated by means of numerical simulations, with a Hamiltonian gyrofluid model. In the linear regime, it is found that ion diamagnetic effects decrease the growth rate of the dominant mode. Increasing ion temperature tends to make the magnetic islands propagate in the ion diamagnetic drift direction. In the nonlinear regime, diamagnetic effects reduce the final width of the island. Unlike the electron density, the guiding center density does not tend to distribute along separatrices and at high ion temperature, the electrostatic potential exhibits the superposition of a small scale structure, related to the electron density, and a large scale structure, related to the ion guiding-center density

Gyrofluid simulations of collisionless reconnection in the presence of diamagnetic effects

The effects of the ion Larmor radius on magnetic reconnection are investigated by means of numerical simulations, with a Hamiltonian gyrofluid model. In the linear regime, it is found that ion diamagnetic effects decrease the growth rate of the dominant mode. Increasing ion temperature tends to make the magnetic islands propagate in the ion diamagnetic drift direction. In the nonlinear regime, diamagnetic effects reduce the final width of the island. Unlike the electron density, the guiding center density does not tend to distribute along separatrices and at high ion temperature, the electrostatic potential exhibits the superposition of a small scale structure, related to the electron density, and a large scale structure, related to the ion guiding-center density

Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction.

[Objectives] To detect the radiosensitivity of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). [Methods] EL4 tumour-bearing C57BL/J mice received 5-bromo-2′-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with γ-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a [10]B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. [Results] Following γ-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced radiosensitivity compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in radiosensitivity in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in radiosensitivity were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a[10]B-carrier, especially L-para-boronophenylalanine-[10]B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells. [Conclusion] The radiosensitivity of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the [10]B-carrier used in the BNCR

Excitation of Kaluza-Klein gravitational mode

We investigate excitation of Kaluza-Klein modes due to the parametric resonance caused by oscillation of radius of compactification. We consider a gravitational perturbation around a D-dimensional spacetime, which we compactify on a (D-4)-sphere to obtain a 4-dimensional theory. The perturbation includes the so-called Kaluza-Klein modes, which are massive in 4-dimension, as well as zero modes, which is massless in 4-dimension. These modes appear as scalar, vector and second-rank symmetric tensor fields in the 4-dimensional theory. Since Kaluza-Klein modes are troublesome in cosmology, quanta of these Kaluza-Klein modes should not be excited abundantly. However, if radius of compactification oscillates, then masses of Kaluza-Klein modes also oscillate and, thus, parametric resonance of Kaluza-Klein modes may occur to excite their quanta. In this paper we consider part of Kaluza-Klein modes which correspond to massive scalar fields in 4-dimension and investigate whether quanta of these modes are excited or not in the so called narrow resonance regime of the parametric resonance. We conclude that at least in the narrow resonance regime quanta of these modes are not excited so catastrophically.Comment: 15 pages LaTeX, submitted to Phys.Rev.

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

Frequent allelic imbalances (AIs) including loss of heterozygosity and microsatellite instability on a specific chromosomal region have been identified in a variety of human malignancies. The objective of our study was to assess the possibility of prognostication and monitoring of oral squamous cell carcinoma (SCC) by microsatellite blood assay. DNA from normal and tumorous tissues and serum DNA obtained at three time points (preoperatively, postoperatively, and 4 weeks postoperatively) from 64 patients with oral SCC was examined at nine microsatellite loci. In all, 38 (59%) DNA samples from tumorous tissues and 52% from serum showed AIs in at least one locus. Patterns of AIs in the serum DNA were matched to those detected in tumour DNA. Of them, AIs were frequently detected preoperatively (44%, 28 of 64), and postoperatively (20%, 13 of 64). Moreover, among 12 cases with AIs during the postoperative period, six had no evidence of an AI 4 weeks postoperatively, and they had no recurrence and were disease free. In contrast, six patients with AI-positive DNA 4 weeks postoperatively have died with distant metastasis within 44 weeks. Thus, our results suggest that the assessment of microsatellite status in the serum DNA could be a useful predictive tool to monitor disease prognosis

Non-Markovian polymer reaction kinetics

Describing the kinetics of polymer reactions, such as the formation of loops and hairpins in nucleic acids or polypeptides, is complicated by the structural dynamics of their chains. Although both intramolecular reactions, such as cyclization, and intermolecular reactions have been studied extensively, both experimentally and theoretically, there is to date no exact explicit analytical treatment of transport-limited polymer reaction kinetics, even in the case of the simplest (Rouse) model of monomers connected by linear springs. We introduce a new analytical approach to calculate the mean reaction time of polymer reactions that encompasses the non-Markovian dynamics of monomer motion. This requires that the conformational statistics of the polymer at the very instant of reaction be determined, which provides, as a by-product, new information on the reaction path. We show that the typical reactive conformation of the polymer is more extended than the equilibrium conformation, which leads to reaction times significantly shorter than predicted by the existing classical Markovian theory.Comment: Main text (7 pages, 5 figures) + Supplemantary Information (13 pages, 2 figures