Thermodynamic limit of the Nekrasov-type formula for E-string theory

We give a proof of the Nekrasov-type formula proposed by one of the authors for the Seiberg-Witten prepotential for the E-string theory on R^4 x T^2. We take the thermodynamic limit of the Nekrasov-type formula following the example of Nekrasov-Okounkov and reproduce the Seiberg-Witten description of the prepotential. The Seiberg-Witten curve obtained directly from the Nekrasov-type formula is of genus greater than one. We find that this curve is transformed into the known elliptic curve by a simple map. We consider the cases in which the low energy theory has E_8, E_7+A_1 or E_6+A_2 as a global symmetry.Comment: 19 pages. v2: title and footnote 1 changed, typos corrected, version to appear in JHE

A case of oncocytic papillary cystadenocarcinoma of the parotid gland—Pathological and molecular features of a rare tumor

AbstractWe present histological, immunohistochemical and molecular features of oncocytic papillary cystadenocarcinoma, a rare neoplasm of the salivary and parotid glands, in an 82-year-old Japanese man. The resected tumor was solid nodular mass with fibrous capsule. The tumor was composed of papillary proliferation of tall columnar cells with thin vascular cores. The cytoplasm of the tumor cells was granular and eosinophilic. The tumor cells showed clear positive reaction for mitochondria and androgen receptor. GCDFP15 and HER2 were negative. Electron microscopy demonstrated numerous mitochondria in the cytoplasm of the tumor cells. Ki-67 index was 30%. Most of the tumor cells were positive for TP53, and single nucleotide polymorphism was found at codon 151. The invasion into the lymphatic spaces and capsule was noted. Although recurrence and metastasis were not noted at one and a half years after the resection, the patient needs to be followed up under careful observation

Sorafenib Prevents Escape from Host Immunity in Liver Cirrhosis Patients with Advanced Hepatocellular Carcinoma

Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200–800 mg/day for 4 weeks. Blood samples were collected before and after treatment. Results. Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. Conclusions. These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC

Stent-Related Adverse Events as Related to Dual Antiplatelet Therapy in First- vs Second-Generation Drug-Eluting Stents

[Background] There are limited data on the long-term stent-related adverse events as related to the duration of dual antiplatelet therapy (DAPT) in second-generation (G2) drug-eluting stents (DES) compared with first-generation (G1) DES. [Objectives] This study sought to compare the long-term stent-related outcomes of G2-DES with those of G1-DES. [Methods] The study group consisted of 15, 009 patients who underwent their first coronary revascularization with DES from the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) Registry Cohort-2 (first-generation drug-eluting stent [G1-DES] period; n = 5, 382) and Cohort-3 (second-generation drug eluting stent [G2-DES] period; n = 9, 627). The primary outcome measures were definite stent thrombosis (ST) and target vessel revascularization (TVR). [Results] The cumulative 5-year incidences of definite ST and TVR were significantly lower in the G2-DES group than in the G1-DES group (0.7% vs 1.4%; P < 0.001; and 16.2% vs 22.1%; P < 0.001, respectively). The lower adjusted risk of G2-DES relative to G1-DES for definite ST and TVR remained significant (HR: 0.53; 95% CI: 0.37-0.76; P < 0.001; and HR: 0.74; 95% CI: 0.68-0.81; P < 0.001, respectively). In the landmark analysis that was based on the DAPT status at 1 year, the lower adjusted risk of on-DAPT status relative to off-DAPT was significant for definite ST beyond 1 year in the G1-DES stratum (HR: 0.42; 95% CI: 0.24-0.76; P = 0.004) but not in the G2-DES stratum (HR: 0.66; 95% CI: 0.26-1.68; P = 0.38) (Pinteraction = 0.14). [Conclusions] G2-DES compared with G1-DES were associated with a significantly lower risk for stent-related adverse events, including definite ST and TVR. DAPT beyond 1 year was associated with a significantly lower risk for very late ST of G1-DES but not for that of G2-DES

Physiological and Ultrastructural Studies on the Origin of Activator Calcium in Body Wall Muscles of Spoon Worms

To examine the origin of activator Ca and its translocation during contraction in body wall muscles (BWM) of spoon worms, Urechis unicinctus , physiological and ultrastructural studies, including cytochemistry, were performed. The potassium (K-) contracture tension was significantly reduced by the removal of external Ca, and by the application of Mn, La and verapamil. On the other hand, caffeine induced a prolonged contraction. The removal of Ca and Mg from the external solution, and the rapid cooling caused an irregular or oscillatory contraction. These results suggested that, in BWM fibers, the activator Ca is supplied partially from both external solution and intracellular Ca-accumulating structures. Ultrastructural observations revealed that the muscle fibers contain a relatively large amount of sarcoplasmic reticulum (SR). The fractional volume of the SR relative to the fiber volume was 2~5% in all fibers of three muscle layers. To demonstrate the Ca localization, the muscle fibers were fixed by pyroantimonate (PA) methods at resting and contracting states. In the resting fibers, the PA precipitates were exclusively localized in the SR and the inner surface of plasma membrane. On the other hand, in the contracting fibers, they were diffusely distributed in the central regions of myoplasm, and had disappeared from the SR and plasma membrane. X-ray microanalysis revealed that the PA precipitates contain Ca. With the results of physiological experiments, these results indicate that the activator Ca originates not only from the external solution, but also from the intracellular Ca-accumulating structures, the SR and the inner surface of plasma membrane.Full-Length Pape

ソウキ ノ ゼンシン ステロイド リョウホウ ニヨリ キドウ ノ ハンコン キョウサク オ カイヒ デキタ キカンシ ケッカク ノ 1ショウレイ

35歳男性.入院約6週前より喀痰,咳嗽出現.数日前に左上肺空洞影指摘,喀痰中抗酸菌(3+)検出され入院.INH,RFP,PZA 及びEB による標準化学療法が開始された.咳嗽,呼吸困難,両肺野狭窄音聴取及び多量排菌持続し,気管支鏡所見上気管&#12316;両側主気管支に隆起性潰瘍病変を認め,気管支結核を確定.高度の呼吸器症状遷延のため中等量のステロイド点滴投与を開始し,症状ならびに気道粘膜病変は改善した.高率に気管・気管支瘢痕収縮へ移行しうる気道粘膜像であったが,中等量の全身ステロイド療法により回避された.気道瘢痕狭窄回避のため,気管支結核活動性病変には中等量以上の全身ステロイド療法を考慮すべきと考えられた.A 35-year-old man admitted to the hospital because of acavitary lesion in the lung and acid-fast bacilli (AFB) (3+) in a sputum specimen, a polymerase-chain-reaction ofwhich revealed positive for M. tuberculosis. He had beenwell until approximately 6 weeks before admission, whenproductive cough developed. He also had temperature of upto 38 ℃, hoarseness, and shortness of breath couple of daysbefore. Intractable cough, dyspnea, wheeze in both lungfields, and numerous AFB in a sputum sustained, despiteprompt introduction of conventional chemotherapy containingINH, rifampicin, pyrazinamide, and ethambutol. Diagnosisof EBTB was confirmed by fibroptic bronchoscopy,which revealed granulomatous ulceration in the mucosa oftrachea and both main bronchi. Accordingly, intravenousmedium-dose methylprednisolone was administered, resultingrelief from serious respiratory manifestation and avoidanceof cicatricial stenosis of trachea and bronchi. This outcomesuggested that the current early intervention withglucocorticoid should be considered in serious active lesionof tracheal and bronchial mucosa in patients with EBTB

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target