Periodic Slow Waves Presenting as Ictal Electroencephalography Findings in Complex Partial Status Epilepticus

The diagnosis of nonconvulsive status epilepticus (NCSE) largely relies on electroencephalography (EEG) findings, but the existing diagnostic criteria for EEG results are sometimes inconsistent. Much debate has centered on periodic epileptic discharges (PEDs) and their relationship with seizures. The recently published Salzburg Consensus Criteria for diagnosis of NCSE, which consider PEDs to be ictal findings under several conditions, have been proven to have high diagnostic accuracy. However, the criteria do not include periodic slow waves (PSWs) and do not consider these as overall ictal electrographic changes. Here, we report 2 cases of complex partial status epilepticus in which routine EEG showed PSWs without epileptiform activity during the clinical ictal phase. Both patients were elderly males who had histories of seizures and presented with impaired consciousness and signs such as aphasia or tongue automatism that indicated a temporal lobe origin. After we administered antiepileptic drugs (AED), the clinical signs and periodic EEG slow waves disappeared. These cases show that PSWs may appear as ictal electrographic changes in NCSE. When PSWs accompany clinical signs suggestive of NCSE, they should be considered ictal findings, and physicians should administer AED

Heerfordt’s Syndrome Associated with a High Fever and Elevation of TNF-α

Heerfordtʼs syndrome is a rare manifestation of sarcoidosis and is defined as a combination of facial palsy, parotid swelling, and uveitis, associated with a low-grade fever. We report a case of Heerfordtʼs syndrome presenting with a high fever and increased serum tumor necrosis factor alpha (TNF-α) levels. The patient had facial palsy, parotid swelling, uveitis, and swelling of the right supraclavicular and hilar lymph nodes. Corticosteroid therapy was initiated, and her symptoms soon resolved completely, in tandem with a decrease in TNF-α serum levels

Costimulatory molecule-deficient dendritic cell progenitors (MHC class II⁺, CD80(dim), CD86^-) prolong cardiac allograft survival in nonimmunosuppressed recipients

We have shown previously that granulocyte-macrophage colony-stimulating factor-stimulated mouse bone marrow-derived MHC class II+ dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD8O) and B7-2 (CD86) can induce alloantigen- specific T-cell anergy in vitro. To test the in vivo relevance of these findings, 2 x 106 B10 (H2(b)) mouse bone marrow-derived DC progenitors (NLDC 145+, MHC class II+, B7-1(dim), B7-2(-/dim)) that induced T-cell hyporesponsiveness in vitro were injected systemically into normal C3H (H2(k)) recipients. Seven days later, the mice received heterotopic heart transplants from B10 donors. No immunosuppressive treatment was given. Median graft survival time was prolonged significantly from 9.5 to 22 days. Median graft survival time was also increased, although to a lesser extent (16.5 days), in mice that received third-party (BALB/c; H2(d)) DC progenitors. Ex vivo analysis of host T-cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed minimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte reactivity. These responses were reduced substantially compared with those of spleen cells from animals pretreated with 'mature' granulocyte- macrophage colony-stimulating factor + interleukin-4-stimulated DC (MHC class II(bright), B7-1+, B7-2(bright)), many of which rejected their heart grafts in an accelerated fashion. Among the injected donor MHC class II+ DC progenitors that migrated to recipient secondary lymphoid tissue were cells that appeared to have up-regulated cell surface B7-1 and B7-2 molecule expression. This observation may explain, at least in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients

Identification of targetable kinases in idiopathic pulmonary fibrosis

Background Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Methods Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). Results Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. Conclusions We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF

TCP/IP スタック ニ オケル チェックサムケイサン ノ GPU オフロード ニ ヨル セイノウ コウジョウ シュホウ

Ethernet Jumbo Frameの登場により、特にデータセンタなどの閉じたネットワーク環境において送受信されるフレームサイズが増大している。フレームサイズの増大に伴い、TCP/IPスタックにおけるチェックサム計算に要するCPU負荷が増大する。本報告では、大きな帯域幅のメモリをもつGraphics Processing Unit (GPU)にチェックサム計算をオフロードすることにより、CPU負荷を削減し、データ転送スループットを向上させる手法を提案する。具体的には、CPU-GPU間のパケット転送効率を向上させるためのパケットキューイング手法、及び、GPU上で複数のパケットを同時処理するためのGPUマルチプロセッサを用いたパケット分散処理手法の2つを提案する。ユーザランドで動作するチェックサム計算の簡易実装により性能を評価し、チェックサム計算のGPUオフロードによって、データ転送性能が最大で13%向上することを示す。The size of ethernet frames is becoming larger and larger due to the utilization of Ethernet Jumbo Frame option, especially in closed network environment such as data center networks. Increasing frame size would cause the large overhead for checksum calculation in TCP /IP protocol processing, that increase the CPU load. In this report we propose the scheme for decreasing CPU load and improving data transmission throughput by offloading checksum calculation to Graphics Processing Unit (GPU). Our scheme consists of the following two methods: packet queueing method to improve the packet transmission throughput between CPU and GPU, and the packet processing method exploiting the advantage of GPU's multiprocessor architecture. We evaluate the performance of the proposed scheme by simple experiments using the user-land implementation and confirm that the proposed scheme can improve the TCP data transmission throughput by 13 %, that is almost the same as the case when the checksum calculation is canceled.坪内佑樹, 長谷川剛, 谷口義明, 中野博隆, 松岡茂登「TCP/IPスタックにおけるチェックサム計算のGPUオフロードによる性能向上手法」『電子情報通信学会技術研究報告』Vol.113, No.244、pp.67-72、電子情報通信学会、201

Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin

X線自由電子レーザーを用いて、光照射によるチャネルロドプシンの構造変化の過程を捉えることに成功. 京都大学プレスリリース. 2021-03-26.Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore

Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease

The transcription factor IRF5 has been implicated as a therapeutic target for the autoimmune disease systemic lupus erythematosus (SLE). However, IRF5 activation status during the disease course and the effects of IRF5 inhibition after disease onset are unclear. Here, we show that SLE patients in both the active and remission phase have aberrant activation of IRF5 and interferon-stimulated genes. Partial inhibition of IRF5 is superior to full inhibition of type I interferon signaling in suppressing disease in a mouse model of SLE, possibly due to the function of IRF5 in oxidative phosphorylation. We further demonstrate that inhibition of IRF5 via conditional Irf5 deletion and a newly developed small-molecule inhibitor of IRF5 after disease onset suppresses disease progression and is effective for maintenance of remission in mice. These results suggest that IRF5 inhibition might overcome the limitations of current SLE therapies, thus promoting drug discovery research on IRF5 inhibitors

Hayabusa2’s superior solar conjunction mission operations: planning and post-operation results

Abstract In late 2018, the asteroid Ryugu was in the Sun’s shadow during the superior solar conjunction phase. As the Sun-Earth-Ryugu angle decreased to below 3°, the Hayabusa2 spacecraft experienced 21 days of planned blackout in the Earth-probe communication link. This was the first time a spacecraft had experienced solar conjunction while hovering around a minor body. For the safety of the spacecraft, a low energy transfer trajectory named Ayu was designed in the Hill reference frame to increase its altitude from 20 to 110 km. The trajectory was planned with the newly developed optNEAR tool and validated with real time data. This article shows the results of the conjunction operation, from planning to flight data.</jats:p