Financial integration in East Asia

This paper examines the degree of integration into world financial markets and the impacts on several key macroeconomic variables of selected East Asian economies, and draws policy implications. According to our analysis, the degrees of integration into world financial markets in those economies are increasing. Regarding the impacts of increasing integration into world financial markets on several macroeconomic variables, we find three results. First, casual two-way plots among macroeconomic variables do not support the theoretical prediction of reduction in relative consumption volatility. Second, the saving-investment correlation is higher than those of in Euro area economies. Third, the degrees of smoothing of idiosyncratic shock by cross-holding of financial assets are lower than Euro area economies. Those results suggest two policy implications. First, there's some room for improvement in welfare gains in those economies by further risk sharing. Second, holding all other conditions given, the increasing integration into world financial markets alone is unlikely to provide a sound ground for a currency union in East Asia at this stage.

Financial Integration in East Asia

This paper examines the degree of integration into world financial markets and the impacts on several key macroeconomic variables of selected East Asian economies, and draws policy implications. According to our analysis, the degrees of integration into world financial markets in those economies are increasing. Regarding the impacts of increasing integration into world financial markets on several macroeconomic variables, we find three results. First, casual two-way plots among macroeconomic variables do not support the theoretical prediction of reduction in relative consumption volatility. Second, the saving-investment correlation is higher than those of the euro area economies. Third, the degrees of smoothing of idiosyncratic shock by cross-holding of financial assets are lower than the euro area economies. These results suggest two policy implications. First, there is some room for improvement in welfare gains in those economies by means of further risk sharing. Second, holding all other conditions equal, the increasing integration into world financial markets alone is unlikely to provide a sound ground for a currency union in East Asia at this stage.Exchange rate regime, financial integration, risk sharing

Glucose transport in interlobular ducts isolated from rat pancreas

Pancreatic duct cells express Na+-dependent glucose transporter, SGLT1 and Na+-independent glucose transporters, GLUT1, GLUT2, and GLUT8. We examined transepithelial glucose transport by pancreatic duct. Interlobular ducts were isolated from rat pancreas. During overnight culture both ends of the duct segments sealed spontaneously. The lumen of the sealed duct was micropunctured and the luminal fluid was replaced by HEPES-buffered solution containing 10.0 mM or 44.4 mM glucose. The bath was perfused with HEPES-buffered solution at 37℃ containing 10.0 or 44.4 mM glucose. Transepithelial differences in osmolality were balanced with mannitol. Glucose transport across ductal epithelium was measured by monitoring changes in luminal volume. When the lumen was filled with 44.4 mM glucose, with either 10.0 or 44.4 mM glucose in the bath, the luminal volume decreased to 65～70% of the initial volume in 15 min. Luminally-injected phlorizin, an inhibitor of SGLT1, abolished the decrease in luminal volume. With 10.0 mM glucose in the lumen and 44.4 mM glucose in the bath, the luminal volume did not change significantly. Luminal application of phlorizin under identical condition led to an increase in luminal volume. The data suggest that both active and passive transport mechanisms of glucose are present in pancreatic ductal epithelium

Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia.

BACKGROUND: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL. METHODS: Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain 3 (BH3) profiling to identify BH3 peptides responsible for treatment resistance in MLL-leukaemia. FINDINGS: Src family kinases (SFKs) and Fms-like tyrosine kinase 3 (FLT3) signaling pathway were over-represented in MLL-ALL cells. PDX-models of infant MLL- ALL recapitulated GC-resistance in vivo but RK-20449, an inhibitor of SFKs and FLT3 eliminated human MLL-ALL cells in vivo, overcoming GC-resistance. Further, we identified BCL-2 dependence as a mechanism of treatment resistance in MLL-ALL through BH3 profiling. Furthermore, MLL-ALL cells resistant to RK-20449 treatment were dependent on the anti-apoptotic BCL-2 protein for their survival. Combined inhibition of SFKs/FLT3 by RK-20449 and of BCL-2 by ABT-199 led to substantial elimination of MLL-ALL cells in vitro and in vivo. Triple treatment combining GCs, RK-20449 and ABT-199 resulted in complete elimination of MLL-ALL cells in vivo. INTERPRETATION: SFKs/FLT3 signaling pathways are promising targets for treatment of treatment-resistant MLL-ALL. Combined inhibition of these kinase pathways and anti-apoptotic BCL-2 successfully eliminated highly resistant MLL-ALL and demonstrated a new treatment strategy for treatment-resistant poor-outcome MLL-ALL. FUNDING: This study was supported by RIKEN (RIKEN President\u27s Discretionary Grant) for FI, Japan Agency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report

CFTR Functions as a Bicarbonate Channel in Pancreatic Duct Cells

Pancreatic duct epithelium secretes a HCO3−-rich fluid by a mechanism dependent on cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane. However, the exact role of CFTR remains unclear. One possibility is that the HCO3− permeability of CFTR provides a pathway for apical HCO3− efflux during maximal secretion. We have therefore attempted to measure electrodiffusive fluxes of HCO3− induced by changes in membrane potential across the apical membrane of interlobular ducts isolated from the guinea pig pancreas. This was done by recording the changes in intracellular pH (pHi) that occurred in luminally perfused ducts when membrane potential was altered by manipulation of bath K+ concentration. Apical HCO3− fluxes activated by cyclic AMP were independent of Cl− and luminal Na+, and substantially inhibited by the CFTR blocker, CFTRinh-172. Furthermore, comparable HCO3− fluxes observed in ducts isolated from wild-type mice were absent in ducts from cystic fibrosis (ΔF) mice. To estimate the HCO3− permeability of the apical membrane under physiological conditions, guinea pig ducts were luminally perfused with a solution containing 125 mM HCO3− and 24 mM Cl− in the presence of 5% CO2. From the changes in pHi, membrane potential, and buffering capacity, the flux and electrochemical gradient of HCO3− across the apical membrane were determined and used to calculate the HCO3− permeability. Our estimate of ∼0.1 µm sec−1 for the apical HCO3− permeability of guinea pig duct cells under these conditions is close to the value required to account for observed rates of HCO3− secretion. This suggests that CFTR functions as a HCO3− channel in pancreatic duct cells, and that it provides a significant pathway for HCO3− transport across the apical membrane

膠原病で検出された160kDaタンパクに対する自己抗体の抗原解析

膠原病では抗核抗体および疾患特異的自己抗体が高率に検出される。それぞれの自己抗体は臨床的特徴を有している。我々は免疫沈降法による自己抗体のスクリーニングにて160kDa蛋白に対する新規自己抗体を検出した。MS解析にて抗原蛋白はscaffold attachment factor Bと判明した。抗SAFB抗体は全身性強皮症や多発性筋炎、皮膚筋炎、間質性肺疾患の患者で認められ、レイノー現象や爪上皮出血点を有していた。抗SAFB抗体は間質性肺疾患に関連した新規膠原病自己抗体であると考えた。Antinuclear antibodies (ANAs) are a hallmark of autoimmune connective tissue diseases(CTD).The CTD-related autoAbs are associated with specific clinical features.During the screening process using immunoprecipitation assays in sera, we found several sera that occasionally reacted with a protein with a molecular weight of 160 kDa. Using a series of biochemical and molecular analyses, the autoantigen targeted by this Ab specificity was identified as scaffold attachment factor B (SAFB).The anti-SAFB Ab was detected in a small number of patients with systemic sclerosis,　polymyositis/dermatomyositis and interstitial lung disease (ILD).Patients with anti-SAFB Ab had Raynaud’s phenomenon and nail fold punctate hemorrhage.Anti-SAFB Ab is a novel CTD-related autoAb possibly associated with ILD.研究課題/領域番号:17K16331, 研究期間(年度):2017-04-01 - 2019-03-31出典：研究課題「膠原病で検出された160kDaタンパクに対する自己抗体の抗原解析」課題番号17K16331（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17K16331/17K16331seika/)を加工して作

統計教育ツールとしての jamovi / Introducing jamovi as a tool for education in statistics.

オープンソースの統計ソフトウェアである jamovi が有償ソフトウェアに比べて，統計教育のためのツールとして何がどのように優れているかを論じ，jamovi による統計分析の例を解説した。/ We proposed that open-source statistical software “jamovi” is a successful candidate of educational tool in statistics, because it has a user-friendly GUI and is based on powerful statistical programming language R. In this paper, we argued the potential benefits of “jamovi” and introduced how it works with typical statistical testing

Successful Second Microsurgical Replantation for Amputated Penis

Summary:. Penile amputation is a rare emergency, but the best method for its repair is required due to the organ’s functional and societal role. Since the first successful microsurgical replantation of the amputated penis, microsurgical techniques have matured and become the standard treatment for the penile replantation. However, the successful second microsurgical replantation for amputated penis has been rarely reported. We present the case of a 40-year-old man with schizophrenia who had a past history of penile self-mutilation and successful replantation at another hospital 2 years ago. After stopping oral medication for schizophrenia, he again cut his penis with a kitchen knife. We successfully replanted the amputated penis by anastomosing both circumflex arteries, the superficial dorsal vein, and the deep dorsal vein using microsurgical techniques. Postoperatively, the foreskin of the replanted penis gradually developed partial necrosis, requiring surgical debridement. The aesthetic and functional results were satisfactory and retrograde urethrography showed no evidence of leakage and stricture of the urethra. Although skin necrosis after penile replantation has been reported as an unavoidable process owing to the nature of injury, the rate would be higher after secondary replantation because of scar formation due to the previous operation. Therefore, our case of successful secondary replantation suggests that skin necrosis would be a predictable postoperative complication and the debridement timing of the devitalized foreskin should be closely monitored, and also secondary amputation is not a contraindication of replantation