Exact WKB analysis of confluent hypergeometric differential equations with a large parameter (Exponential Analysis of Differential Equations and Related Topics)

"Exponential Analysis of Differential Equations and Related Topics". October 15～18, 2013. edited by Yoshitsugu Takei. The papers presented in this volume of RIMS Kôkyûroku Bessatsu are in final form and refereed.Voros coefficients of the confluent hypergeometric differential equations (the Kummer equation or the Whittaker equation) with a large parameter are defined and explicit forms of them are obtained

Physical, functional and conditional interactions between ArcAB and phage shock proteins upon secretin-induced stress in Escherichia coli

The phage shock protein (Psp) system found in enterobacteria is induced in response to impaired inner membrane integrity (where the Psp response is thought to help maintain the proton motive force of the cell) and is implicated in the virulence of pathogens such as Yersinia and Salmonella. We provided evidence that the two-component ArcAB system was involved in induction of the Psp response in Escherichia coli and now report that role of ArcAB is conditional. ArcAB, predominantly through the action of ArcA regulated genes, but also via a direct ArcB–Psp interaction, is required to propagate the protein IV (pIV)-dependent psp-inducing signal(s) during microaerobiosis, but not during aerobiosis or anaerobiosis. We show that ArcB directly interacts with the PspB, possibly by means of the PspB leucine zipper motif, thereby allowing cross-communication between the two systems. In addition we demonstrate that the pIV-dependent induction of psp expression in anaerobiosis is independent of PspBC, establishing that PspA and PspF can function as a minimal Psp system responsive to inner membrane stress

Protein kinase Cγ negatively regulates the intrinsic excitability in zebrin-negative cerebellar Purkinje cells

Protein kinase C γ (PKCγ), a neuronal isoform present exclusively in the central nervous system, is most abundantly expressed in cerebellar Purkinje cells (PCs). Targeted deletion of PKCγ causes a climbing fiber synapse elimination in developing PCs and motor deficit. However, physiological roles of PKCγ in adult mouse PCs are little understood. In this study, we aimed to unravel the roles of PKCγ in mature mouse PCs by deleting PKCγ from adult mouse PCs of PKCγfl/fl mice via cerebellar injection of adeno-associated virus (AAV) vectors expressing Cre recombinase under the control of the PC-specific L7-6 promoter. Whole cell patch-clamp recording of PCs showed higher intrinsic excitability in PCs virally lacking PKCγ [PKCγ-conditional knockout (PKCγ-cKO) PCs] than in wild-type (WT) mouse PCs in the zebrin-negative module, but not in the zebrin-positive module. AAV-mediated PKCγ re-expression in PKCγ-deficient mouse PCs in the zebrin-negative module restored the enhanced intrinsic excitability to a level comparable to that of wild-type mouse PCs. In parallel with higher intrinsic excitability, we found larger hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in PKCγ-cKO PCs located in the zebrin-negative module, compared with those in WT mouse PCs in the same region. However, pharmacological inhibition of the HCN currents did not restore the enhanced intrinsic excitability in PKCγ-cKO PCs in the zebrin-negative module. These results suggested that PKCγ suppresses the intrinsic excitability in zebrin-negative PCs, which is likely independent of the HCN current inhibition

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

Botulinum Neurotoxin for Pain Management: Insights from Animal Models

The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models

緊急事態宣言時における武庫川女子大学子育てひろばの取り組み

　本研究の目的は，緊急事態宣言時における武庫川女子大学子育てひろばの取り組みを紹介することである。2020 年3月3 日～5 月29 日の期間，武庫川女子大学子育てひろばは新型コロナウイルス感染症予防や政府の緊急事態宣言のため臨時休館した。臨時休館中は地域の子育て家庭は来館できないため，武庫川女子大学子育てひろばは，地域の子育て家庭に向けて，①子育てひろば利用者への手紙の発送，②子育てひろば職員による電話での子育て相談，③SNS（Facebook）を通じた支援，を実施した。今後の課題として，①これらの取り組みの効果検証の実施，②再び休館した際のさらなる取り組みの検討，③子育てひろば再開後の事業展開のあり方，が挙げられた

在留外国人の健康維持に必要な災害時の支援

　近年，全国各地で自然災害が起こっているが，在留外国人はコミュニケーション・ギャップなどにより，災害弱者になりやすいとされている。しかし，彼らが災害時に居住する地域で心身の健康を維持するために必要な支援について，明らかになっていない。そこで，本研究は，災害時に在留外国人にどのような支援が必要かを明らかにすることを目指す。まず，岡山県内の在留外国人（国籍別にベトナム27名，インドネシア12名，中国11名，その他34名）を対象に質問紙調査を行った。さらに，質問紙回答者の内３名に対し，半構造化面接による調査を行った。その結果，災害時の物資について，在留外国人特有の要望は認められなかった。しかし，医療サービスへのアクセスに不安を持ち，多言語対応の医療情報などを強く求めていることが明らかになった。また，相談できる病院がないという回答は57.1％にのぼり，災害時の医療支援については70.2％が，災害マニュアルの存在については83.3％が認識していなかった。これらの調査の結果から，医学生が理解しなければならないことが明らかになった。まず，在留外国人には，災害時の支援の情報収集に課題があることである。国際社会における医療の現状と課題の理解は，『医学教育モデル・コア・カリキュラム』の「国際社会への貢献」の項目に示されているものである。次に，災害時に医療サービスを円滑に提供するために，平時から外国人医療について理解しなければならないことである。そのためには，患者の文化的背景を尊重し，異なる言語や価値観に対応した医療を提供するための素養を身に付けることが必要となる。これらを実践するためには，医学部のカリキュラムとして，大学全体で地域の在留外国人の診療や災害時の支援に関する学修を行う必要があると考える。　Recently, Japan has faced various natural disasters throughout the country, and foreign residents have tended to be vulnerable victims due to factors such as the communication gap. Nevertheless, disaster assistance for maintaining their health at their residential areas has not been adequately discussed. This study aims to determine the assistance needed to maintain foreign residents\u27 health at the time of a disaster. A questionnaire survey was administered to foreign residents in Okayama Prefecture (27 Vietnamese, 12 Indonesians, 11 Chinese, and 34 other nationals), and then semistructured interviews were conducted with three persons among the above-stated participants. The results showed that foreign residents were concerned about the access to medical services and that they had a strong need for multilingual medical information, whereas no relief supplies needed particularly by foreign residents was identified. It was also revealed that 57. 1 percent of the participants did not have any medical institution to consult with during a disaster, 70.2 percent did not have information about disaster-related medical support, and 83.3 percent were not aware of disaster guidelines. These findings suggest two issues that medical students need to be aware of. First, foreign residents have problems in collecting disaster assistance information. We maintain that medical students should understand such situations, as the importance of understanding the current medical situation and issues in the global society are discussed in the section “Contribution to the Global Society" in the Model Core Curriculum for Medical Education in Japan. It is also suggested that medical doctors need to have sufficient knowledge on healthcare for foreigners under any circumstance and need to be able to provide medical services smoothly during a disaster. In order to do so, they should be equipped with an attitude and knowledge for practicing medicine that respects the patients\u27 cultural background and accommodates diverse languages and values. The curriculum for medical education should offer opportunities to learn about community health care including foreign patients and disaster assistance

An Excellent Monitoring System for Surface Ubiquitination-Induced Internalization in Mammals

Background. At present, it is difficult to visualize the internalization of surface receptors induced by ubiquitination that is taken place at the plasma membrane in mammals. This problem makes it difficult to reveal molecular basis for ubiquitinationmediated internalization in mammals. Methodology/Principle Findings. In order to overcome it, we have generated T-REx-c-MIR, a novel mammalian Tet-on B cell line using a constitutively active E3 ubiquitin ligase, c-MIR, and its artificial target molecule. By applying the surface biotinylation method to T-REx-c-MIR, we succeeded to monitor the fate of surface target molecules after initiation of ubiquitination process by doxycycline (Dox)-induced c-MIR expression. Target molecules that preexisted at the plasma membrane before induction of c-MIR expression were oligo-ubiquitinated and degraded by Dox-induced c-MIR expression. Dox-induced c-MIR expression initiated rapid internalization of surface target molecules, and blockage of the internalization induced the accumulation of the surface target molecules that were newly ubiquitinated by c-MIR. Inhibition of the surface ubiquitination by down-regulating ubiquitin conjugating enzyme E2 impaired the internalization of target molecules. Finally, a complex of c-MIR and target molecule was detected at the plasma membrane. Conclusions/ Significances. These results demonstrate that in T-REx-c-MIR, surface target molecule is ubiquitinated at the plasma membrane and followed by being internalized from the plasma membrane. Thus, T-REx-c-MIR is a useful experimental tool t

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements