Magnetization dependent current rectification in (Ga,Mn)As magnetic tunnel junctions

We have found that the current rectification effect in triple layer (double barrier) (Ga,Mn)As magnetic tunnel junctions strongly depends on the magnetization alignment. The direction as well as the amplitude of the rectification changes with the alignment, which can be switched by bi-directional spin-injection with very small threshold currents. A possible origin of the rectification is energy dependence of the density of states around the Fermi level. Tunneling density of states in (Ga,Mn)As shows characteristic dip around zero-bias indicating formation of correlation gap, the asymmetry of which would be a potential source of the energy dependent density of states

Fairness Scheduling in Dense User-Centric Cell-Free Massive MIMO Networks

We consider a user-centric scalable cell-free massive MIMO network with a total of $LM$ distributed remote radio unit antennas serving $K$ user equipments (UEs). Many works in the current literature assume $LM\gg K$, enabling high UE data rates but also leading to a system not operating at its maximum performance in terms of sum throughput. We provide a new perspective on cell-free massive MIMO networks, investigating rate allocation and the UE density regime in which the network makes use of its full capability. The UE density $K$ approximately equal to $\frac{LM}{2}$ is the range in which the system reaches the largest sum throughput. In addition, there is a significant fraction of UEs with relatively low throughput, when serving $K>\frac{LM}{2}$ UEs simultaneously. We propose to reduce the number of active UEs per time slot, such that the system does not operate at ``full load'', and impose throughput fairness among all users via a scheduler designed to maximize a suitably defined concave componentwise non-decreasing network utility function. Our numerical simulations show that we can tune the system such that a desired distribution of the UE throughput, depending on the utility function, is achieved

Overloaded Pilot Assignment with Pilot Decontamination for Cell-Free Systems

The pilot contamination in cell-free massive multiple-input-multiple-output (CF-mMIMO) must be addressed for accommodating a large number of users. In previous works, we have investigated a decontamination method called subspace projection (SP). The SP separates interference from co-pilot users by using the orthogonality of the principal components of the users' channel subspaces. Non-overloaded pilot assignment (PA), where each radio unit (RU) does not assign the same pilot to different users, limits the spectral efficiency (SE) of the system, since SP channel estimation is able to deal with co-pilot users that have nearly orthogonal subspaces. Motivated by this limitation, this paper introduces overloaded PA methods adjusted for the decontamination in order to improve the sum SE of CF systems. Numerical simulations show that the overloaded PA methods give higher SE than that of non-overloaded PA at a high user density scenario.Comment: 7 pages, 2 figures, this paper was submitted to IEEE WCNC 202

ADAMTS13によるvon Willebrand因子の切断増加は、本態性血小板血症患者における後天性von Willebrand症候群の発症に強く寄与する。

Background: Patients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased. Objective: We investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET. Methods: Seventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF-related parameters. We calculated the VWFM index, defined as the ratio of intensities of a patient's molecular weight-categorized VWFMs, and those of a healthy subject's, using densitometric analysis. VWF degradation product (DP) was measured via ELISA using a monoclonal antibody that specifically recognizes Y1605 at the C-terminal boundary, which is exposed following ADAMTS13-mediated cleavage of the Y1605-M1606 bond of the VWF A2 domain. Results: Patients with higher platelet counts had a significantly reduced high molecular weight (HMW)-VWFM index and an increased VWF-DP: VWF antigen (Ag) ratio compared to those with lower platelet counts. On multivariate analysis, the VWF-DP/ VWF:Ag ratio was an independent predictor of the HMW-VWFM index. Patients who underwent cytoreductive therapy had a significantly higher HMW-VWFM index and lower VWF-DP/ VWF:Ag ratio than those who did not. Among individual patients, there was also a significant increase in the HMW-VWFM index and a decrease in the VWF-DP/ VWF:Ag ratio after cytoreductive therapy compared to pre-therapy values. Conclusion: In patients with ET, an increased platelet count is associated with enhanced cleavage of VWF at the Y1605-M1606 bond, primarily by ADAMTS13, leading to AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWF cleavage, and improves VWFM distributions.博士（医学）・甲第881号・令和5年3月15

Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

Abstract4H-1-benzopyran-4-ones (chromones) are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E)-3-(4-hydroxystyryl)-6-methoxy-4H-chromen-4-one (compound 11), (E)-6-methoxy-3-(4-methoxystyryl)-4H-chromen-4-one (compound 4), (E)-6-methoxy-3-(3,4,5-trimethoxystyryl)-4H-chromen-4-one (compound 6) showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC) lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs

A genome-wide gain-of-function analysis of rice genes using the FOX-hunting system

Funding Information: Acknowledgements This work was supported by a grant from the Ministry of Agriculture, Forestry and Fisheries of Japan (Green Technology Project EF-1004). We are grateful to Dr. Takuji Sasaki for his encouragement throughout the project and his excellent advice on the improvement of this manuscript, and to Dr. Shoshi Kikuchi for providing useful information on rice FL-cDNAs. We thank Professors Kokichi Hinata, Atsushi Hirai, Hiroshi Kamada and Masashi Ugaki for their encouragement, critical comments and helpful suggestions, and Drs. Hisato Okuizumi and Hiroyuki Kawahigashi for their administrative support throughout the project. We also thank Mayumi Akagawa, Hiroko Abe, Keiko Mori, Etsuko Sugai, Yumiko Nakane, Ken-ichi Watanabe, Mayumi Takeya, and Kana Miyata for their technical assistance; the members of the Technical Support Section of the National Institute of Agrobiological Sciences for their help in the care of the FOX-rice plants; Haruko Onodera and Kazuko Ono for their technical assistance and advice on rice transformation; Inplanta Innovations Inc. for their technical help on the construction of theThe latest report has estimated the number of rice genes to be ∼32 000. To elucidate the functions of a large population of rice genes and to search efficiently for agriculturally useful genes, we have been taking advantage of the Full-length cDNA Over-eXpresser (FOX) gene-hunting system. This system is very useful for analyzing various gain-of-function phenotypes from large populations of transgenic plants overexpressing cDNAs of interest and others with unknown or important functions. We collected the plasmid DNAs of 13 980 independent full-length cDNA (FL-cDNA) clones to produce a FOX library by placing individual cDNAs under the control of the maize Ubiquitin-1 promoter. The FOX library was transformed into rice by Agrobacterium-mediated high-speed transformation. So far, we have generated approximately 12 000 FOX-rice lines. Genomic PCR analysis indicated that the average number of FL-cDNAs introduced into individual lines was 1.04. Sequencing analysis of the PCR fragments carrying FL-cDNAs from 8615 FOX-rice lines identified FL-cDNAs in 8225 lines, and a database search classified the cDNAs into 5462 independent ones. Approximately 16.6% of FOX-rice lines examined showed altered growth or morphological characteristics. Three super-dwarf mutants overexpressed a novel gibberellin 2-oxidase gene, confirming the importance of this system. We also show here the other morphological alterations caused by individual FL-cDNA expression. These dominant phenotypes should be valuable indicators for gene discovery and functional analysis.publishersversionPeer reviewe

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI

Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules

Objective: To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA). Method: This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patientyears (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan-Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied. Results: The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE. Conclusions: Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept