Josephson junction in cobalt-doped BaFe2As2 epitaxial thin films on (La, Sr)(Al, Ta)O3 bicrystal substrates

Josephson junctions were fabricated in epitaxial films of cobalt-doped BaFe2As2 on [001]-tilt (La,Sr)(Al,Ta)O3 bicrystal substrates. 10m-wide microbridges spanning a 30-degrees-tilted bicrystal grain boundary (BGB bridge) exhibited resistively-shunted-junction (RSJ)-like current-voltage characteristics up to 17 K, and the critical current was suppressed remarkably by a magnetic field. Microbridges without a BGB did not show the RSJ-like behavior, and their critical current densities were 20 times larger than those of BGB bridges, confirming BGB bridges display a Josephson effect originating from weakly-linked BGB

DC superconducting quantum interference devices fabricated using bicrystal grain boundary junctions in Co-doped BaFe2As2 epitaxial films

DC superconducting quantum interference devices (dc-SQUIDs) were fabricated in Co-doped BaFe2As2 epitaxial films on (La, Sr)(Al, Ta)O3 bicrystal substrates with 30deg misorientation angles. The 18 x 8 micro-meter^2 SQUID loop with an estimated inductance of 13 pH contained two 3 micro-meter wide grain boundary junctions. The voltage-flux characteristics clearly exhibited periodic modulations with deltaV = 1.4 micro-volt at 14 K, while the intrinsic flux noise of dc-SQUIDs was 7.8 x 10^-5 fai0/Hz^1/2 above 20 Hz. The rather high flux noise is mainly attributed to the small voltage modulation depth which results from the superconductor-normal metal-superconductor junction nature of the bicrystal grain boundary

Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor

Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Base

Combination of panobinostat with ponatinib synergistically overcomes imatinib-resistant CML cells

The major mechanism of imatinib (IM) resistance of CML is the reactivation of ABL kinase either through BCR-ABL gene amplification or mutation. We investigated the cytotoxicity of a pan-ABL tyrosine kinase inhibitor, ponatinib, and a pan-histone deacetylase inhibitor, panobinostat, against IM-resistant CML cells in vitro. Two different IM-resistant cell lines, K562/IM-R1 and Ba/F3/T315I were evaluated in comparison with their respective, parental cell lines, K562 and Ba/F3. K562/IM-R1 overexpressed BCR-ABL due to gene amplification. Ba/F3/T315I was transfected with a BCR-ABL gene encoding T315I-mutated BCR-ABL. Ponatinib inhibited the growth of both K562/IM-R1 and Ba/F3/T315I as potently as it inhibited their parental cells with an IC50 of 2-30 nM. Panobinostat also similarly inhibited the growth of all of the cell lines with an IC50 of 40-51 nM. This was accompanied by reduced histone deacetylase activity, induced histone H3 acetylation, and an increased protein level of heat shock protein 70, which suggested disruption of heat shock protein 90 chaperone function for BCR-ABL and its degradation. Importantly, the combination of ponatinib with panobinostat showed synergistic growth inhibition and induced a higher level of apoptosis than the sum of the apoptosis induced by each agent alone in all of the cell lines. Ponatinib inhibited phosphorylation not only of BCR-ABL but also of downstream signal transducer and activator of transcription 5, protein kinase B, and ERK1/2 in both K562/IM-R1 and Ba/F3/T315I, and the addition of panobinostat to ponatinib further inhibited these phosphorylations. In conclusion, panobinostat enhanced the cytotoxicity of ponatinib towards IM-resistant CML cells including those with T315I-mutated BCR-ABL

Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group

[Background] Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. [Aim] This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. [Methods and results] Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P = .002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P = .006). [Conclusions] The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT

C57BL/KsJ-db/db-ApcMin/+ Mice Exhibit an Increased Incidence of Intestinal Neoplasms

The numbers of obese people and diabetic patients are ever increasing. Obesity and diabetes are high-risk conditions for chronic diseases, including certain types of cancer, such as colorectal cancer (CRC). The aim of this study was to develop a novel animal model in order to clarify the pathobiology of CRC development in obese and diabetic patients. We developed an animal model of obesity and colorectal cancer by breeding the C57BL/KsJ-db/db (db/db) mouse, an animal model of obesity and type II diabetes, and the C57BL/6J-ApcMin/+ (Min/+) mouse, a model of familial adenomatous polyposis. At 15 weeks of age, the N9 backcross generation of C57BL/KsJ-db/db-ApcMin/+ (db/db-Min/+) mice developed an increased incidence and multiplicity of adenomas in the intestinal tract when compared to the db/m-Min/+ and m/m-Min/+ mice. Blood biochemical profile showed significant increases in insulin (8.3-fold to 11.7-fold), cholesterol (1.2-fold to 1.7-fold), and triglyceride (1.2-fold to 1.3-fold) in the db/db-Min/+ mice, when compared to those of the db/m-Min/+ and m/m-Min/+ mice. Increases (1.4-fold to 2.6-fold) in RNA levels of insulin-like growth factor (IGF)-1, IRF-1R, and IGF-2 were also observed in the db/db- Min/+ mice. These results suggested that the IGFs, as well as hyperlipidemia and hyperinsulinemia, promoted adenoma formation in the db/db-Min/+ mice. Our results thus suggested that the db/db-Min/+ mice should be invaluable for studies on the pathogenesis of CRC in obese and diabetes patients and the therapy and prevention of CRC in these patients

Efficacy and safety of garenoxacin tablets on clinically diagnosed atypical pneumonia: Postmarketing surveillance in Japan

We performed a postmarketing surveillance study to determine the efficacy and safety of the oral quinolone antibacterial agent garenoxacin (Geninax R Tablets 200 mg) against atypical pneumonia. Between October 2009 and July 2011, patients with community-acquired pneumonia visited 26 facilities in Japan; we collected survey forms from 105 of these patients who were suspected of having atypical pneumonia based on the Japanese Respiratory Society Guidelines for the Management of Community-Acquired Pneumonia in Adults. We examined the safety in 105 patients and the efficacy in 71 patients. 1. The efficacy rates among patients suspected of having atypical pneumonia and those with a confirmed diagnosis of atypical pneumonia were 94.8% (55/58 patients) and 92.3% (12/13 patients), respectively. The efficacy rate was 4/4 for patients in whom Chlamydophila pneumoniae was detected (including 1 patient with a polymicrobial infection with another bacterial strain) and 90% (9/10 patients) for patients in whom Mycoplasma pneumoniae was detected (garenoxacin was ineffective in 1 of 2 patients with a polymicrobial infection with another bacterial strain). 2. The incidence of adverse drug reactions (including abnormal laboratory tests) was 4.8% (5/105 patients). Among the adverse drug reactions, gastrointestinal disorders, infection and infestation, nervous system disorder, and skin and subcutaneous tissue disorder were observed in 2.9% of patients (3/105), 1.0% (1/105), 1.0% (1/105), and 1.0% (1/105), respectively. In conclusion, garenoxacin showed an efficacy rate of greater than 90% for suspected atypical pneumonia and confirmed atypical pneumonia. Garenoxacin is considered to be useful in daily practice

Formation and morphological change of BaTaO2N perovskite from BaCN2/Ta2O5 mixture

Metal oxynitrides are generally synthesized by heating their component oxides in a flow of ammonia for longer than 20 h. In the present study, pure BaTaO2N oxynitride perovskite powder was obtained by heating a mixture of tetragonal BaCN2 and Ta2O5 in a flow of nitrogen. The BaTaO2N powder synthesized at slightly below the melting point of tetragonal BaCN2 (910 degrees C) was found to consist of coarse aggregates of 300 nm-sized particles based on scanning electron microscopy observations. In contrast, BaTaO2N powder obtained above the melting point of tetragonal BaCN2 contained highly-dispersed particles after washing with acid. This difference is attributed to the dissolution and precipitation of the surfaces of the BaTaO2N grains in the BaCN2 melt to generate grain boundary layers soluble in acid. This work represents the first report of the synthesis of a metal oxynitride using a metal carbodiimide as both the metal and nitrogen source. (C) 2020 Elsevier B.V. All rights reserved

Spark plasma sintering of dielectric BaTaO2N close to the melting point of the BaCN2 additive

The perovskite-type oxynitride BaTaO2N is a promising lead-free relaxor ferroelectric material. However, this material releases a part of its nitrogen during its sintering above 1350 degrees C. Subsequent annealing of the resulting sintered BaTaO2N0.85 ceramics under an ammonia flow is necessary to recover an insulating, stoichiometric BaTaO2N ceramics. Very recently, molten BaCN2 was reported to be a useful flux for the preparation of BaTaO2N microcrystals without the loss of nitrogen. In the present work, BaTaO2N powder was sintered with a BaCN2 additive under mechanical pressure, using a spark plasma sintering system. Nitrogen loss from the BaTaO2N ceramic was avoided during liquid phase sintering at approximately 900 degrees C. The stoichiometric BaTaO2N ceramic product with a relative density of 79.8 % was an electrically insulator and it showed its relative dielectric constants, epsilon(r) in the range from 320 to 650 and a loss tans values from 0.04 to 0.19 at room temperature