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Abstract Neoadjuvant therapy with nivolumab improves event‐free survival (EFS) in patients with resectable non‐small cell lung cancer, and a pathological complete response is a predictor of longer EFS. We assessed metabolic responses using 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) before and after neoadjuvant treatment to explore its surrogacy for pathological complete response (pCR). We describe three patients with squamous cell lung carcinoma who underwent neoadjuvant therapy with nivolumab plus chemotherapy, followed by surgery. In Cases 1 and 2, preoperative tumour response were PR per RECIST and demonstrated marked metabolic response on FDG‐PET after neoadjuvant therapy, with both resected tumours showing a pCR. On the other hand, Case 3 showed a tumour response before surgery (PR per RECIST), however, the tumour, maintained FDG uptake (19.5 → 15.1), and the resected tumour remained residual cells (RVT, 15%). Thus, reduction of FDG uptake on FDG‐PET can predict the pathological response to neoadjuvant therapy with nivolumab.

Gold-catalyzed propargylic substitution of propargylic alcohols 1 with 1,3-dicarbonyl compounds 2 followed by cycloisomerization in ionic liquid enables the environmentally friendly synthesis of polysubstituted furans 3 in good-to-high yields. The reaction proceeds via the hydrated propargylic substitution product 3″aa. The gold catalyst can be recycled at least three times.

To prepare high-performance copper-based composites, Y2O3/W multiphase reinforced copper-based composites were synthesized through mechanical alloying and spark plasma sintering, and the mole ratio of W and Y2O3 was explored. It is found that the incorporation of W inhibited the growth of copper particle during ball milling, and facilitated the refinement of Y2O3. Compared to conditions without W addition, the Y2O3 particle diameter reduced from 97.96 nm to 33.4 nm when same mole W was added. Furthermore, copper grains were refined, resulting in a higher tensile strength of 305 MPa and elongation of 15.6 %. At 400 °C, the 5:5 sample exhibited a higher thermal conductivity of 299 W/(m·K). Nano-scale particles were uniformly distributed within the copper matrix, and the interaction between W and Y2O3 inhibited nanoparticle coarsening, leading to the formation of a more stable Y2WO6 phase during sintering, which is also better for the purification of the copper matrix.

Abstract The standard treatment for resectable non‐small cell lung cancer (NSCLC) located in the superior sulcus is neoadjuvant chemoradiotherapy followed by highly invasive resection. Based on the results of the CheckMate 816 trial, which showed a marked improvement in the efficacy of neoadjuvant chemo‐immunotherapy, we report a case of minimally invasive resection after neoadjuvant nivolumab plus chemotherapy for superior sulcus NSCLC, resulting in a pathologic complete response. The patient was a 76‐year‐old man with a 65‐mm right superior sulcus tumour diagnosed as squamous cell carcinoma with 95% PD‐L1. After two courses of neoadjuvant nivolumab plus chemotherapy, the tumour was completely resected through an 11‐cm right lateral thoracotomy with second rib resection and first rib preservation. No residual tumour cells were observed in the specimen, and the patient had a pathologic complete response. This report represents a new treatment option for superior sulcus tumours.

A research facility for neutron irradiation effect on superconducting materials has been installed at Oarai center in Tohoku University in 2012 as part of a post irradiation experiment. It consists of a 15.5 T superconducting magnet, a variable temperature insert and a data acquisition and control system. Since the sample holder is cooled by thermal conduction with G-M refrigeration, there is a small temperature difference between positive and negative electrodes and the sample temperature rises during the critical current test due to joule heating. To evaluate the temperature rise precisely, a new data acquisition system with a sampling rate of 50 Hz has been installed. By measuring the temperatures of both electrodes and the voltage at the center of the sample, the temperature of the sample was estimated and the measured critical current (IC) was converted to the current at 4.2 K with a critical surface equation. The comparison of IC at different conditions including neutron irradiated samples was implemented and the neutron irradiation effect on superconductivity of Nb3Sn wire is discussed based on the 4.2 K superconductivity. This paper will describe the outline of the new data acquisition system and some results of neutron irradiated Nb3Sn wires.

Two types of Cu composites containing 3 wt% Y2O3, with and without a process control agent (PCA), were fabricated using mechanical alloying (MA) and hot isostatic pressing (HIP). The results showed that the addition of PCA effectively inhibited the growth of MA powders. This was attributed to the PCA forming a lubricating film on the MA powders, preventing adhesion between the powders. However, residual PCA after heat treatments contained C impurities, which had a significant impact on thermal conductivity. The lubricating film weakened the binding force between MA powders during sintering, resulting in poor mechanical performance. Additionally, the lubricating film slowed down the MA process by eliminating the frictional stress caused by oblique collision. Frictional stress plays a crucial role in the dissolution of Y into the Cu matrix due to the tearing of Y-rich particles and the fracture of MA powders. Therefore, it is necessary to explore an optimum PCA that can be easily removed before sintering, slow down the growth of MA powders, and avoid reducing the efficiency of the MA process during the synthesis of Cu-Y2O3 composites by mechanical alloying.

One-pot synthesis of (E)-5-[bromo(phenyl)methylene]-4-phenyl-2-(p-tolyl)-4,5-dihydrooxazole (9) from propargylic alcohol 5 and p-toluamide (6) was achieved via gold(III)-catalyzed propargylic substitution, followed by gold(III)-catalyzed bromocyclization. The structure of 9 was confirmed by an X-ray crystallographic analysis.

Abstract Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N-formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.5 Å apart unlike canonical FAD-dependent oxidoreductases. One site could accommodate glycine and the other glycinothricin or glycylthricin. Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. The chain length of nucleophilic acceptors vies with bond cleavage sites at either N–O or O–S accounting for N-formimidoylation or N-iminoacetylation. The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species.

Bacteria-derived polycationic homopoly(amino acid)s are reported for the first time to directly penetrate cell membrane and deliver proteins of interest into cells, representing a new type of cell penetrating peptides for intracellular delivery.

Abstract A 72‐year‐old man was diagnosed with hypercalcaemia 13 years ago. He was diagnosed with hyperparathyroidism associated with a parathyroid tumour and surgery was performed. Postoperatively, his serum calcium levels, which had once normalized, rose again. Medical treatment for hypercalcaemia failed to control the condition. A chest computed tomography showed multiple pulmonary nodules which were diagnosed as pulmonary metastases of parathyroid carcinoma. The tumour was considered to be the cause of the hypercalcaemia and volume reduction surgery was performed. Immediately after surgery, the patient presented with hypocalcaemia and required calcium correction with Calcium Gluconate Hydrate. Since then, the serum calcium level has stabilized and the patient has progressed without medical treatment. Parathyroid carcinoma is rare. This is a valuable case in which the serum calcium level was controlled by surgery. The patient also developed post‐operative hypocalcaemia, which should be reported.

Objectives Descending necrotizing mediastinitis (DNM) is a poor prognosis disease. This study aims to examine the patient background and treatment of DNM and to identify more effective treatments for DNM.

The treatment of N-tosylpropargyl amines 1 with 1,3-dicarbonyl compounds 2 in the presence of AuBr3 (5 mol%) and AgOTf (15 mol%) afforded poly-substituted furans 3 in good-to-high yields via the gold-catalyzed cleavage of the sp3 carbon–nitrogen bond.

MgB2 represents a hexagonal superconductive material renowned for its straightforward composition, which has facilitated the development of cost-effective practical wires. Its capacity to function at temperatures as low as liquid hydrogen (LH2) has made it a prominent candidate as wire material for the coils of next-generation fusion reactors. Much like other superconducting wires, a prevalent issue arises when these wires are employed in coils, wherein electromagnetic forces induce tensile stress and strain within the wire. This, in turn, diminishes the critical current, which is the maximum current capable of flowing within the generated magnetic field and strain. The techniques and methods for accurately measuring the actual strain on the filaments are of paramount importance. While strain measurements have been conducted with synchrotron radiation and neutrons for other practical wires in the past, no such measurements have been undertaken for MgB2. Presumably, this lack of measurement is attributed to its relatively greater thickness, making it less suitable for synchrotron radiation measurements. Additionally, the high absorption cross-section of the included boron-10 poses challenges in obtaining elastic scattering data for neutron measurements. In response, we fabricated a wire enriched with boron-11, an isotope with a smaller neutron absorption cross-section. We then embarked on the endeavor to measure its strain under tensile loading using pulsed neutrons. Consequently, we succeeded in obtaining changes in the lattice constant under tensile loading through Rietveld analysis. This marks the inaugural instance of strain measurement on an MgB2 filament, signifying a significant milestone in superconductivity research.

By strategic use of the valence difference between hard gold(III) and soft gold(I) catalysts, one-pot synthesis of (Z)-5-benzylidene-4-phenyl-2-(p-tolyl)-4,5-dihydrooxazole (15) from propargylic alcohol (9) and p-toluamide (13) was achieved via gold(III)-catalyzed propargylic substitution followed by gold(I)-catalyzed cyclization. The structure of 15 was confirmed by X-ray crystallographic analysis.

To refine the dispersive Y2O3 particles and to explore the optimum Y2O3 content, reducing the Y2O3 addition from 1.5 wt% to 0.5 wt% for Cu6Y sourced Cu-Y2O3 was investigated. It was found that reducing the Y2O3 addition had little influence on the number density, while reducing the size of the Y2O3 particles. Compared with the Y2O3 addition, the nucleation point is expected to be more important for the number density of the Y2O3 by the in-situ fabrication method. Moreover, reducing the Y2O3 addition indeed thinned the prior particle boundaries with O enrichment and contamination, thereby improving the mechanical performance and thermal conductivity. It was calculated that dispersion strengthening made great a contribution to the increment of the yield strength for ODS-Cu. While, the large particles with contamination on the prior particle boundaries induced the dimples and the premature micro-cracks, deteriorating the tensile performance. Therefore, the performance of Cu6Y sourced ODS-Cu can be improved once further reduces the introduction of contamination and suppresses the growth of MA powders during MA process.

Abstract Pulmonary nocardiosis is a rare disease that is often difficult to cure because of its tendency to recur. Here, we report a case of refractory localized pulmonary nocardiosis caused by Nocardia mexicana. A 60‐year‐old Japanese woman had recurring pulmonary nocardiosis four times previously and each time she was treated with antibiotics for a sufficient duration; nevertheless, the disease continued to recur, probably because of resistance to antibiotics. As a fifth treatment, we performed middle lobe resection and pre‐ and post‐operative antimicrobial therapy for 6 months. The combination of medication and surgery was useful for treating refractory localized pulmonary nocardiosis

Four V-Ta-4Cr-4Ti quaternary alloys containing different quantities of Ta were investigated to determine the effect of Ta content on the Charpy impact properties. Five button-shaped ingots of the V-4Cr-4Ti ternary alloy and V-xTa-4Cr-4Ti quaternary alloys (x = 3, 9, 15, and 22 wt.%) were fabricated on a laboratory scale by using non-consumable arc-melting in an argon atmosphere. Charpy impact tests were conducted at temperatures ranging from 77 K to 293 K using an instrumented impact tester. Both the upper shelf energy and the ductile–brittle transition temperature increased with increasing Ta content. The addition of 3 wt.% Ta resulted in solid solution strengthening without any degradation of the Charpy impact properties. Thus, the addition of 3 wt.% Ta (V-3Ta-4Cr-4Ti) is an appropriate amount to use in blanket structural materials for nuclear fusion reactors. The spectra of TEM-EDS for V-3Ta-4Cr-4Ti quaternary alloy indicate that there is no significant enrichment of Ta in the matrix as compared with that in the precipitate. However, thermal aging may result in the formation of the Laves phase, causing the degradation of Charpy impact properties. The characterization of precipitates, thermal aging, and creep tests of the V-3Ta-4Cr-4Ti quaternary alloy need to be investigated to determine the optimum Ta content.

Abstract A 71‐year‐old man, who was found to have a posterior mediastinal tumour, was referred to our hospital. Contrast‐enhanced computed tomography (CT) showed a 15‐cm soft tissue shadow in the posterior mediastinum, with many affected areas and a gradually increasing pattern. We also detected oligemic areas with poor contrast‐filling. There was no invasion into the adjacent vertebral body and the blood vessels penetrating the interior were intact. Positron emission tomography–CT revealed a high maximum standardized uptake level of 4.53 in the mediastinal masses. We performed thoracoscopic surgery for the biopsy. Histological findings showed lymphoplasmacytic infiltration in the fibrous stroma as well as storiform fibrosis. Immunohistochemical examination revealed abundant infiltration of immunoglobulin G4 (IgG4)‐positive plasma cells and 40% IgG4/IgG‐positive plasma cells. Postoperative serum examinations showed a high serum IgG4 level (570 mg/dl). Accordingly, we diagnosed the patient with IgG4‐related fibrosing mediastinitis, a rare manifestation of IgG4‐related disease.

Abstract The occurrence of lipoma in the thoracic cavity is relatively rare, and it is clinically difficult to distinguish it from liposarcoma. We report a case of intrathoracic lipoma that was pathologically diagnosed and differentiated from liposarcoma after minimally invasive thoracoscopic tumour resection. A 35‐year‐old male patient without any symptoms was referred to our hospital due to an abnormal shadow on chest x‐ray. Computed tomography showed a low‐attenuated round‐shaped mass of 3.6 cm × 2.3 cm in diameter in the left chest wall. On magnetic resonance imaging, the mass was displayed as a high, high and low signal mass on T1‐weighted imaging (WI), T2WI and T2WI with fat suppression, respectively. We suspected a chest wall‐type lipoma, but because it appeared in a relatively short period of time and we thought it could be liposarcoma, we performed minimally invasive thoracoscopic surgery for diagnosis and treatment. The tumour was a stalked tumour with a capsule, contiguous to the wall pleura with only a single cord‐like structure. The majority of the tumour was found free in the pleural cavity. The tumour was diagnosed as a lipoma by histopathological examination.

Abstract A 63‐year‐old woman was diagnosed with tuberculous bronchial stenosis of the left main bronchus following recurrent pneumonia. She underwent airway dilatation and stenting for long and severe stenosis. Initially, a Dumon Y‐stent was implanted, but repeated granulation occurred at the distal end of the stent. The granulation reappeared repeatedly despite cauterization and stent replacement. An attempt at stent removal led to worsening of scar stenosis; therefore, it was reinstalled. Finally, two self‐expandable metallic stents were implanted sequentially, and she remained asymptomatic for 14 months. After this, she presented with fever and a computed tomography showed obstructive pneumonia due to associated granulation at the distal end of the stent. She was then started on tranilast to treat the granulation with the stent in situ. Granulation almost completely disappeared after 4 months and no recurrence was noted at 12 months since the start of tranilast.

Functional ceramic coatings have been investigated for several decades to mitigate tritium permeation through structural materials in a fusion reactor blanket. For the establishment of a liquid blanket system, the coatings require not only tritium permeation reduction but also the tolerance to irradiation damage induced by neutrons and corrosion by liquid tritium breeders. In this study, deuterium permeation measurements under exposure to liquid lithium–lead were performed for a heavy-ion-irradiated zirconium oxide coating sample to elucidate the synergy of irradiation and corrosion on hydrogen isotope permeation. The irradiated coating decreased the deuterium permeation flux under lithium–lead exposure by more than two orders of magnitude in comparison with the unirradiated one. Each activation energy of permeation and diffusion of the coating sample was larger than that of the unirradiated one at around 450 °C and decreased to the level of the unirradiated one at 600 °C. The results indicated that the voids formed by ion irradiation aggregated in grain boundaries of the coating, resulting in an increase in the energy barrier of diffusion at low temperatures and then a decrease due to the defect recovery at high temperatures. Besides, a corrosion product layer formed on the coating during lithium–lead exposure increased the energy barrier of solution. The synergy of irradiation and corrosion on permeation was developed at lower temperatures before the defect recovery.

Abstract Capillary haemangioma is a rare condition that is difficult to diagnose preoperatively because of its rarity and nonspecific imaging findings. In this report, we describe a case of capillary haemangioma diagnosed by robot‐assisted thoracic surgery (RATS). A 72‐year‐old man was incidentally found to have an anterior mediastinal tumour on chest computed tomography. The preoperative imaging findings were indicative of thymoma, and surgical treatment by RATS was selected. The intraoperative findings suggested that the tumour was a haemangioma originating from the pericardiophrenic vein. The pathological findings revealed a well‐defined tumour with capillaries in a vascular‐like structure and some thrombus formation. The pathological diagnosis was capillary haemangioma. The patient was discharged unaided at 7 days postoperatively and no recurrence was observed at 16 months postoperatively.

Abstract A 72‐year‐old man was diagnosed as having myasthenia gravis (MG). He underwent computed tomography which revealed an anterior mediastinal tumour. Laboratory examination revealed elevated levels (106.3 U/ml) of carbohydrate antigen (CA) 19‐9 in serum. However, no malignant disease was detected on fluorodeoxyglucose‐positron emission tomography. A diagnosis of thymoma associated with MG was considered and an extended thymectomy was performed. Histopathologically, thymoma was categorized as stage I based on the Masaoka classification, and as type AB according to the World Health Organization classification. Immunohistochemistry was positive for CA 19‐9. The serum levels returned to the normal range post‐operatively (16.7 U/ml). Herein, we report an extremely rare case of thymoma with raised levels of CA 19‐9.

We recently disclosed that the biosynthesis of antiviral γ-poly-D-2,4-diaminobutyric acid (poly-D-Dab) in Streptoalloteichus hindustanus involves an unprecedented cofactor independent stereoinversion of Dab catalyzed by PddB, which shows weak homology to diaminopimelate epimerase (DapF). Enzymological properties and mechanistic details of this enzyme, however, had remained to be elucidated. Here, through a series of biochemical characterizations, structural modeling, and site-directed mutageneses, we fully illustrate the first Dab-specific PLP-independent racemase PddB and further provide an insight into its evolution. The activity of the recombinant PddB was shown to be optimal around pH 8.5, and its other fundamental properties resembled those of typical PLP-independent racemases/epimerases. The enzyme catalyzed Dab specific stereoinversion with a calculated equilibrium constant of nearly unity, demonstrating that the reaction catalyzed by PddB is indeed racemization. Its activity was inhibited upon incubation with sulfhydryl reagents, and the site-directed substitution of two putative catalytic Cys residues led to the abolishment of the activity. These observations provided critical evidence that PddB employs the thiolate-thiol pair to catalyze interconversion of Dab isomers. Despite the low levels of sequence similarity, a phylogenetic analysis of PddB indicated its particular relevance to DapF among PLP-independent racemases/epimerases. Secondary structure prediction and 3D structural modeling of PddB revealed its remarkable conformational analogy to DapF, which in turn allowed us to predict amino acid residues potentially responsible for the discrimination of structural difference between diaminopimelate and its specific substrate, Dab. Further, PddB homologs which seemed to be narrowly distributed only in actinobacterial kingdom were constantly encoded adjacent to the putative poly-D-Dab synthetase gene. These observations strongly suggested that PddB could have evolved from the primary metabolic DapF in order to organize the biosynthesis pathway for the particular secondary metabolite, poly-D-Dab. The present study is on the first molecular characterization of PLP-independent Dab racemase and provides insights that could contribute to further discovery of unprecedented PLP-independent racemases.

Dispersion-strengthened (DS) copper alloys with Y2O3 particles are known as high strength and high thermal conductivity materials having potential for heat sink materials of fusion devices. In the previous study on mechanical alloying (MA) and hot isostatic pressing (HIP) processing of DS-Cu alloys, the MA powders showed various morphology and size distribution which influenced the properties of the MA-HIP samples. In this study, the MA alloyed powders with 3 wt% Y2O3 particles were classified by their size and characterized. The particles ranged from fine particles of under 46 μm to coarse particles of 212 μm over, and a wide particle size distribution was confirmed. The peeled Cu-O fragments from coarser MA powders are the main source of finer grain with 46 μm. The finer grains had oxide-like behavior as microstructural and mechanical properties. On the other hand, the coarser powder having over 212 μm had metal-like behavior as microstructural and mechanical properties. We thought that the classification of the MA powder before HIP process was one of the suitable process to optimize the microstructure and several properties of ODS-Cu alloy.

For the establishment of liquid tritium breeding concepts, static lithium-lead corrosion tests for single-layer erbium oxide coatings and erbium oxide-metal multi-layer coatings were carried out, followed by deuterium permeation measurements. Grain boundary corrosion of erbium oxide coatings was confirmed by the static immersion tests at 550 and 600 °C. An erbium oxide-iron two-layer coating sustained its structure after lithium-lead immersion at 600 °C for up to 3000 h. The results of gas-driven deuterium permeation measurements for multi-layer coatings immersed at 550 and 600 °C indicated that crystallization and grain growth of erbium oxide would sufficiently occur during the immersion at 600 °C, and then the sample showed lower permeabilities in the first measurements at lower temperature. On the other hand, permeation reduction factors of the sample immersed at 550 °C were estimated to be 100‒200 in the temperature range of 400‒550 °C. A corrosion layer formed on the coating surface might work as an additional diffusion barrier after the permeation test at 600 °C. Keywords: Lithium-lead, Tritium permeation barrier, Corrosion, Erbium oxide

Abstract Although the incidence of hepatobiliary enzyme abnormality increased immediately after the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident, longer-term trends remain unclear. The aims of this study were to determine longer-term trends in hepatobiliary enzyme abnormality and to elucidate lifestyle factors associated with such changes among residents of a nuclear-disaster-affected area. This longitudinal survey enrolled 20,395 adults living in the vicinity of Fukushima Daiichi Nuclear Power Plant. Data were obtained from the records of annual health checkups of adults aged ≥40 years between 2011 and 2012. Follow-up examinations were conducted from June 2013 to March 2014. Associations were assessed between changes in hepatobiliary enzyme abnormality immediately and 3–4 years after the disaster and lifestyle factors. The overall prevalence of hepatobiliary enzyme abnormality significantly decreased over the study period, from 29.9% to 27.1%. Multivariate logistic regression analysis revealed significant associations between improved hepatobiliary enzyme abnormality and improvements in daily physical activity and frequency of breakfast consumption. The results suggest that improvements in daily physical activity and frequency of breakfast consumption significantly reduced the incidence of hepatobiliary enzyme abnormality 3–4 years after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident.

We previously reported that the lifestyle of evacuees significantly increased the prevalence of polycythemia compared with non-evacuees at an average of 1.6 years (2011–2012) from the previous annual health checkup before the Great East Japan Earthquake (GEJE). Here we analyzed how the prolonged evacuation affected the prevalence of polycythemia an average of 2.5 years (2013–2014) after the previous data. Subjects were individuals aged 40–90 years living in the vicinity of the Fukushima Daiichi Nuclear Power Plant in Fukushima Prefecture who had attended the annual health checkups since 2008. The prevalence of polycythemia and changes in its defining factors of red blood cell count (RBC), hemoglobin (Hb) level, hematocrit (Ht) level were compared between before and after the GEJE in 7713 individuals (3349 men and 4364 women) receiving follow-up examinations both 2011–2012 and 2013–2014. RBC, Hb levels and Ht levels in 2011–2012 were higher among evacuees than non-evacuees in both men and women. However, all levels in 2013–2014 were on the decline from those in 2011–2012. On the other hand, among evacuees, Hb and Ht levels continued to be higher than before the GEJE in both men and women evacuees. The prevalence of polycythemia, which was diagnosed if one of the defining factors was beyond the standard value, was significantly higher among evacuees than non-evacuees regardless of the presence or the absence of overweight/obesity, smoking, and hypertension. Therefore, prolonged evacuation is a cause of polycythemia even 3 to 4 years after the GEJE and regular health management of evacuees is important.

Purpose: Hormesis is a phenomenon of growth stimulation at low doses and inhibition at higher doses. In cancer treatment, little is known about how hormesis affects cancer cell proliferation. We evaluated the hormetic dose–response relationship of paclitaxel using surgically resected breast cancer specimens on the basis of histoculture drug response assay (HDRA). Methods: We used surgically resected fresh tumor specimens from 22 patients with breast cancer: 17 invasive ductal, 3 mucinous, and 2 other “special-type” cancers. All patients were female, ranging in age between 40 and 86 (median 60) years. Small pieces of viable cancer tissue were placed on collagen gel and cultured for 7 days with paclitaxel. Inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose–response curve. Results: Hormesis was observed in 9 of the 22 cases; ED 50 of cytotoxic effect was significantly higher ( P = .0036) in hormesis (H) group (44.6 ± 4.2 µg/mL) than in nonhormesis (N) group (26.7 ± 3.5 μg/mL). Conclusion: We evaluated hormesis in breast cancer tissue using HDRA for the first time although previously confirmed in cultured cells. Hormesis seems to occur in patients undergoing treatment with anticancer agents, especially in a metastatic setting. Meanwhile, tumor growth may be stimulated in patients who are resistant to paclitaxel.

A new high strength bonding method between Tungsten (W) and Oxide Dispersion Strengthening copper (ODS-Cu) using vanadium (V) and gold (Au) inserts was investigated and the resulting joints were characterized with SEM, micro-hardness and four point bending test. For the joints using thick Au inserts (300µm), a hardened reaction layer was observed in the V/Au interface region. On the other hand, the joints using thin Au inserts (0.7µm) exhibited a serrated interface layer having homogeneous hardness profiles. In this case, the observed behavior is a reflection of degradation of melting point by inter-diffusion between Au and Cu. Room temperature bending test of the joints with and without 0.7µm inserts at interface between V and ODS-Cu exhibited yielding behavior with the strength of approximately 300MPa which is close to that of ODS-Cu. The joint with the thin Au insert had a serrated interface which implies appearance of liquid phase by reaction between Au and Cu.

Many pharmacologically important peptides are bacterial or fungal in origin and contain nonproteinogenic amino acid (NPA) building blocks. Recently, it was reported that, in bacteria, a cyclopropane-containing NPA 1-aminocyclopropanecarboxylic acid (ACC) is produced from the L-methionine moiety of S-adenosyl-L-methionine (SAM) by non-canonical ACC-forming enzymes. On the other hand, it has been suggested that a monomethylated ACC analogue, 2-methyl-ACC (MeACC), is derived from L-valine. Therefore, we have investigated the MeACC biosynthesis by identifying a gene cluster containing bacterial MeACC synthase genes. In this gene cluster, we identified two genes, orf29 and orf30, which encode a cobalamin (B12)-dependent radical SAM methyltransferase and a bacterial ACC synthase, respectively, and were found to be involved in the MeACC biosynthesis. In vitro analysis using their recombinant enzymes (rOrf29 and rOrf30) further revealed that the ACC structure of MeACC was derived from the L-methionine moiety of SAM, rather than L-valine. In addition, rOrf29 was found to catalyze the C-methylation of the L-methionine moiety of SAM. The resulting methylated derivative of SAM was then converted into MeACC by rOrf30. Thus, we demonstrate that C-methylation of SAM occurs prior to cyclopropanation in the biosynthesis of a bacterial MeACC (norcoronamic acid).

Lead lithium alloy (Pb-17Li) is one of the candidate tritium breeders of fusion reactors. Lead bismuth eutectic alloy (LBE) is one of the candidate materials for the coolant of fast reactors and the target of accelerator driven systems. The functional layers such as an anti-corrosion layer and a tritium permeation barrier have been developed to be applied in these liquid metal systems. Zirconium oxide (ZrO2) are considered to be the candidate material of the functional layers due to its excellent chemical stability. The online monitoring of oxygen potential in the liquid metals is essential technology. The development of in-situ analysis technique for the layer properties in the liquid metals at high temperature is important issue. The purpose of the present study is to develop the on-line monitoring system for the oxygen potential and the layer properties both by the solid electrolyte (SE) oxygen sensor and the electrochemical impedance spectroscopy (EIS). The YSZ type SE sensor and the ZrO2/Zr specimen for the EIS were simultaneously immersed to liquid Pb at 698-898K. The responses of the oxygen sensor and the EIS were successfully obtained, and these signals indicated that the ZrO2 oxide layer is thermodynamically stable in liquid Pb. The EIS response was evaluated based on some equivalent circuit models as the oxide layer had a lot of horizontal cracks in its structure. The influence of the cracks on the capacitance is larger than that on the electrical resistance, when the covering ratio of the cracks in the layer is low. The influence on the electrical resistant becomes larger when the ratio is close to 100%.

We report a case of primary clear-cell sarcoma (CCS) in the mediastinum. In October 2011, a 63-year-old man was admitted to our hospital for surgical resection. The tumor was completely excised by video-assisted thoracoscopic surgery. The tumor was well encapsulated and did not invade the pleura. Histological examination led to a final diagnosis of primary CCS in the mediastinum. The patient remains alive without evidence of recurrence at 15 months after surgery.

Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4–6 months of age) and late phase (7–12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.

A 62-year-old woman with breast cancer received neoadjuvant chemotherapy followed by breast-conserving surgery and sentinel node biopsy. During adjuvant endocrine therapy with aromatase inhibitor, she developed multiple bone metastases. Thereafter, she received tamoxifen and zoledronate therapy. In May 2011, she developed a tongue deviation and was diagnosed as having meningeal carcinomatosis. The tongue deviation disappeared 3 weeks after taking capecitabine (2,400 mg/day). Magnetic resonance imaging of the brain showed regression of meningeal carcinomatosis. Levels of tumor markers CEA and CA15-3 changed from 96.0 IU/ml and 3.5 ng/ml to 47.0 IU/ml and 1.5 ng/ml, respectively. Progression-free survival with capecitabine monotherapy was 5 months.

Background and study aims: Despite the clinical advantages of colorectal endoscopic submucosal dissection (ESD), an effective training system, especially for Western endoscopists, has been challenging to establish. Herein, we propose a novel training program using ex vivo animal models and evaluate the learning curve of colorectal ESD trainees without gastric ESD experience. Patients and methods: A total of 80 colorectal lesions were prospectively collected and removed by two novice operators. Before human ESD procedures, they received ESD training using an ex vivo porcine “proximal colon” model, which simulates a lumen with many folds and flexions. To assess the validity of our training system, the self-completion and en bloc R0 resection rates, the operation time, and prevalence of complications were compared between the first and latter period. Moreover the factors associated with prolonged operation time were evaluated. Results: The overall rates of self-completion and en bloc R0 resection were 98 % (78/80) and 100 % (80/80), respectively. The operation time during the first period was significantly longer than that during the latter period (86 ± 50 minutes vs. 60 ± 36 minutes, P = 0.01). Regarding complications, only two cases of perforations and delayed hemorrhage were observed during the first period; however, all of the complications were successfully managed endoscopically. The presence of fibrosis was identified as a significant independent predictor of a prolonged operation time during the first period (coefficient, 5.90; 95 %CI, 2.36 – 9.44, P = 0.002). Conclusions: Our trainees achieved high rates of self-completion and R0 resection without severe complications even during the first 20 cases, suggesting that our training programs using ex vivo animal models are useful for trainees without gastric ESD experience. Study registration: UMIN000013566

The surface of a Fe-Ni-Cr Alloy (SUS316L) plate was electrochemically nitrided in molten LiF-KF salt including Li3N at 873K. The crystal structure changed from fcc structure to bct structure with nitrogen introduction. The Nitrogen diffusion layers were predominately formed at nitrogen concentration of 23 at%. The nitriding process drastically also changed its magnetic property from non-magnetic to ferromagnetic. The magnetic field of 20 kOe saturated the magnetic moment with its magnetization of 81 emu/g at 10K. The anisotropic magnetization is ascertained. Based on CrN formation and Cr extraction from the original Fe-Ni-Cr system, the induced ferromagnetism was discussed.

We studied sound generated by a diagonally arranged fin in a uniform flow. We set 2-dimensional computational model which neglected spanwise effect of the fins, and performed direct simulation of aerodynamic sound for two types of fins whose difference is the width of the back section with the finite-difference lattice Boltzmann method. Conditions of numerical results in which strong resonance occurred consisted with experimental results and Parker type resonance appeared. When the resonance occurred, the frequency of Kármán vortex shedding from the trailing edges of the fins agreed with the natural frequency of air columns which correspond the space between neighbouring fins. The phase differences between the neighbouring columns were completely “anti-phase” and the same was true for the vortex shedding. We also show the temporal and spacial variations in far sound field which are caused by the asymmetric arrangement of the fins. We also noted that the radiations of sounds of two different frequency existed for high speed flow range.

BACKGROUND: Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD). METHODS: Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis. RESULTS: Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004). CONCLUSIONS: Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.

Many clinically useful pharmaceuticals are semi-synthesized from natural products produced by actinobacteria and fungi. The synthetic protocols usually contain many complicated reaction steps and thereby result in low yields and high costs. It is therefore important to breed microorganisms that produce a compound most suitable for chemical synthesis. For a long time, desirable mutants have been obtained by random mutagenesis and mass screening. However, these mutants sometimes show unfavorable phenotypes such as low viability and low productivity of the desired compound. Fusicoccin (FC) A is a diterpene glucoside produced by the fungus Phomopsis amygdali. Both FC and the structurally-related cotylenin A (CN) have phytohormone-like activity. However, only CN exhibits anti-cancer activity. Since the CN producer lost its ability to proliferate during preservation, a study on the relationship between structure and activity was carried out, and elimination of the hydroxyl group at position 12 of FC was essential to mimic the CN-like activity. Based on detailed dissection of the biosynthetic machinery, we constructed a mutant producing a compound without a hydroxyl group at position 12 by gene-disruption. The mutant produced this compound as a sole metabolite, which can be easily and efficiently converted into an anti-cancer drug, and its productivity was equivalent to the sum of FC-related compounds produced by the parental strain. Our strategy would be applicable to development of pharmaceuticals that are semi-synthesized from fungal metabolites.