Activated partial thromboplastin time‑based clot waveform analysis enables measurement of very low levels of factor IX activity in patients with severe hemophilia B

The precise measurement of very low levels of factor IX activity (FIX:C < 1 IU/dL) is essential for understanding clinical severity and risk of inhibitor development in patients with severe hemophilia B (Pw-SHB). However, such measurement sensitivity has not yet been achieved. We aimed to establish a measurement method using clot waveform analysis (CWA). Residual FIX:C by adding anti-FIX monoclonal antibody, FIX:C by adding recombinant (r)FIX to the commercial Pw-SHB plasmas, and FIX:C in our Pw-SHB were determined by CS-2000i™/CS-2400™, followed by analysis of CWA parameters. The presence of anti-FIX antibody in the commercial Pw-SHB plasmas significantly decreased coagulation potential compared to its absence. The addition of rFIX to these innate plasma samples produced significant changes in three parameters upon adding FIX:C at 0.1–1 IU/dL, supporting the presence of trace FIX:C in Pw-SHB. Therefore, appropriate FIX-depleted plasma containing minimum residual FIX:C was chosen from reference curves of FIX:C (0.01–1 IU/dL). Among patients with untreated Pw-SHB, two had FIX:C 0.6–0.7 IU/dL and two had lower than detectable levels using FIX-depleted plasma. One of the latter had detectable trough levels post-rFIX administration. In conclusion, CWA enabled measurement of very low levels of FIX:C using appropriate FIX-deficient plasma.博士（医学）・乙第1528号・令和4年12月22

Reducing nonideal to ideal coupling in random matrix description of chaotic scattering: Application to the time-delay problem

We write explicitly a transformation of the scattering phases reducing the problem of quantum chaotic scattering for systems with M statistically equivalent channels at nonideal coupling to that for ideal coupling. Unfolding the phases by their local density leads to universality of their local fluctuations for large M. A relation between the partial time delays and diagonal matrix elements of the Wigner-Smith matrix is revealed for ideal coupling. This helped us in deriving the joint probability distribution of partial time delays and the distribution of the Wigner time delay.Comment: 4 pages, revtex, no figures; published versio

組織因子惹起-トロンボモジュリン添加凝固波形解析を用いたプロテインC経路異常を伴う血栓性素因のスクリーニング法

Objectives: Absolute or relative protein (P)C pathway abnormalities (PC deficiency, PS deficiency, antiphospholipid syndrome (APS), factor (F)V-abnormality, and high FVIII level) cause thrombophilia. Although screening assays for these thrombophilias are available, one utilizing clot waveform analysis (CWA) remains unknown. We aimed to establish a CWA-based screening assay to distinguish PC pathway abnormality-related thrombophilia. Methods: Samples were reacted with tissue factor (TF)/phospholipids and recombinant thrombomodulin (rTM; optimal 20 nM), followed by CWA measurement. The peak ratio (with/without rTM) of the first derivative curve of clot waveform was calculated. Results: The peak ratio in healthy plasmas (n = 35) was 0.36 ± 0.13; hence, the cutoff value was set to 0.49. The peak ratios in plasmas with PC deficiency, PS deficiency, high-FVIII (spiked 300 IU/dl), and APS were higher than the cutoff values (0.79/0.97/0.50/0.93, respectively). PC-deficient plasma or PS-deficient plasma mixed with normal plasma (25%/50%/75%/100% PC or PS level) showed dose-dependent decreases in the peak ratios (PC deficient: 0.85/0.64/0.44/0.28; PS deficient: 0.69/0.53/0.40/0.25), suggesting that the peak ratio at ≤50% of PC or PS level exceeded the cutoff value. The peak ratio in FV deficiency with FV ≤25% was higher than the cutoff value. FV-deficient plasma spiked with 40 IU/dl rFV-R506Q (FVLeiden ) or rFV-W1920R (FVNara ) showed >90% peak ratios. Conclusions: rTM-mediated TF-triggered CWA might be useful for screening PC pathway abnormality-related thrombophilia.博士（医学）・乙第1527号・令和4年9月28日© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.This is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/ejh.13777], which has been published in final form at [https://doi.org/10.1111/ejh.13777]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.発行元が定める登録猶予期間終了の後、本文を登録予定（2023.07

AC resistivity of d-wave ceramic superconductors

We model d-wave ceramic superconductors with a three-dimensional lattice of randomly distributed $\pi$ Josephson junctions with finite self-inductance. The linear and nonlinear ac resistivity of the d-wave ceramic superconductors is obtained as function of temperature by solving the corresponding Langevin dynamical equations. We find that the linear ac resistivity remains finite at the temperature $T_p$ where the third harmonics of resistivity has a peak. The current amplitude dependence of the nonlinear resistivity at the peak position is found to be a power law. These results agree qualitatively with experiments. We also show that the peak of the nonlinear resistivity is related to the onset of the paramagnetic Meissner effect which occurs at the crossover temperature $T_p$, which is above the chiral glass transition temperature $T_{cg}$.Comment: 7 eps figures, Phys. Rev. B (in press

High-Energy Electron Transfer Dissociation (HE-ETD) Using Alkali Metal Targets for Sequence Analysis of Post-Translational Peptides

Post-translational modifications (PTMs) of proteins are important in the activation, localization, and regulation of protein function in vivo. The usefulness of electron capture dissociation (ECD) and electron-transfer dissociation (ETD) in tandem mass spectrometry (MS/MS) using low-energy (LE) trap type mass spectrometer is associated with no loss of a labile PTM group regarding peptide and protein sequencing. The experimental results of high-energy (HE) collision induced dissociation (CID) using the Xe and Cs targets and LE-ETD were compared for doubly-phosphorylated peptides TGFLT(p)EY(p)VATR (1). Although HE-CID using the Xe target did not provide information on the amino acid sequence, HE-CID using the Cs target provided all the z-type ions without loss of the phosphate groups as a result of HE-ETD process, while LE-ETD using fluoranthene anion gave only z-type ions from z5 to z11. The difference in the results of HE-CID between the Xe and Cs targets demonstrated that HE-ETD process with the Cs target took place much more dominantly than collisional activation. The difference between HE-ETD using Cs targets and LE-ETD using the anion demonstrated that mass discrimination was much weaker in the high-energy process. HE-ETD was also applied to three other phosphopeptides YGGMHRQEX(p)VDC (2: X = S, 3: X = T, 4: X = Y). The HE-CID spectra of the doubly-protonated phosphopeptides (= [M + 2H]2+) of 2, 3, and 4 using the Cs target showed a very similar feature that the c-type ions from c7 to c11 and the z-type ions from z7 to z11 were formed via N–Cα bond cleavage without a loss of the phosphate group

Surgical Treatment of a Giant Liposarcoma in a Japanese Man

We report a case of a rapidly progressing giant retroperitoneal liposarcoma weighing 22 kg in a 41-year-old Japanese man, successfully treated with surgical excision. To our knowledge, this is the largest liposarcoma in the Japanese population reported in the literature

A Terrestrial SER Estimation Methodology based on Simulation coupled with One-Time Neutron Irradiation Testing

電子機器の信頼性評価の迅速化に光明 --様々な中性子施設で半導体ソフトエラー評価を可能にする技術を開発--. 京都大学プレスリリース. 2023-06-08.Terrestrial soft error rates (SERs) are generally estimated by performing an experiment using spallation neutron beam with the energy spectrum being similar to that of the terrestrial neutrons or at least four measurements using various (quasi-)mono-energetic neutron and/or proton sources to determine the parameters of the Weibull function. We here propose a method to estimate the terrestrial SERs based on simulation coupled with one-time neutron irradiation testing which can be applied to various kinds of neutron sources. In this method, the dependences of single event upset (SEU) cross sections on the neutron energy and the critical charge are calculated by simulation using Particle and Heavy Ion Transport code System (PHITS). The critical charge is used as the only calibration parameter, which is adjusted to reproduce the SER measured by one-time neutron irradiation. The validity of our method is investigated for 65-nm bulk SRAMs with the measured data using various neutron sources in Japan. Our method generally provides the reasonable terrestrial SERs compared with those obtained by the Weibull function method. This result indicates the feasibility of evaluating the terrestrial SER using one of the various neutron sources available all over the world, including those not dedicated to SER measurement. We also investigate the necessity of the elaborated geometry of device under test (DUT) for the accuracy of the simulation. It is shown that detailed material compositions of DUT are not necessary in our method except when the one-time irradiation is performed using the neutron source that contains a high-quantity of low-energy neutrons below 8 MeV. Furthermore, we confirm that the configuration of the sensitive volume can be simplified without sacrificing the estimation accuracy. These simplifications in the simulation help to reduce the modeling and calculation cost in SER estimation