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Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up.ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint.Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib.Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.

BackgroundIL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA) and is elevated in serum and synovial fluid of RA patients.Sarilumab (SRL), a human anti-human IL-6 receptor alpha monoclonal antibody that blocks the signaling originated by the IL-6/IL-6R complex like tocilizumab (TCZ),is an effective treatment. Recently, an association between the therapeutic effect of TCZ and neutropenia after TCZ initiation was reported[1]. Neutropenia is a common adverse event of SRL in patients with RA, but the relationship between reduced neutrophil count and clinical response to SRL is still inconclusive. In EULAR 2020, we reported the association between serum soluble gp130 levels before SRL treatment and the efficacy of SRL[2]. It is also unclear whether there is a relationship between IL-6 axis cytokines and SRL-induced neutropenia.ObjectivesThe purpose of this study was to determine whether neutropenia at 1 month by SRL predicts clinical remission within 3 months and whether there is an association between IL-6 axis cytokines levels and SRL-induced neutropenia.MethodsThis research is a retrospective study. We reviewed medical records of RA patients initiating SRL between February 2018 and August 2021 in our hospital. The Clinical Disease Activity Index (CDAI) was evaluated at baseline (before initiating SRL) and 3 months after administration. Clinical remission was defined when CDAI decreased ≤ 2.8. Of the 66 patients treated with SRL, 42 patients with 3 months follow-up, valid CDAI and serum available were enrolled. The ratio of neutrophil counts 1 month after initiating SRL to those at baseline (neutrophil ratio) was also calculated. Serum samples were tested for IL-6 (Human IL-6 Quantikine ELISA Kit, R&D systems), sIL-6R (Human soluble IL-6R alpha Quantikine ELISA Kit, R&D systems) and sgp130 (Human soluble gp130 Quantikine ELISA Kit, R&D systems) using specific ELISAs according to the manufacturer’s instructions. The statistical analyses were performed with EZR 1.55, and p values less than 0.05 were considered significant.ResultsThe median age of patients was 69.0 (IQR: 59.3 - 73.8) years and the median of disease duration was 9.0 (3.0 - 16.0) years. Eighteen (42.9%) patients were biologics and Jakinibs naive. The baseline CDAI was median 16.7 (11.5 - 25.8). When comparing CDAI-remission group (clinical remission: CR) and non-CR group, Patients in the CR group had significantly shorter disease duration, were more Biologic and JAKinib naive, and had greater neutropenia 1 month after starting SRL (0.71 vs 0.94, P=0.0252). There was no significant difference in the baseline serum levels of IL-6, sIL-6R between the CR and non-CR groups, but baseline serum sgp130 levels in the CR group tended to be higher than in the non-CR group (264.9 vs 234.2 ng/mL, P=0.0592). Univariate logistic regression analysis suggested Biologics and JAKinibs naive (odds ratio (OR) 6.68, p = 0.0317), baseline serum sgp130 levels (OR 8.608, P=0.0312) as predictors of CDAI remission treated with SRL at 3 months. Although not significant, neutrophil ratio ≤ 0.8 was associated with achieving remission (OR 6.67, P=0.0537). Univariate logistic regression for neutrophil ratio ≤ 0.8 did not show any relevant factors, including higher baseline serum sgp130 levels (OR 1.25, P=0.782).ConclusionA 20% or greater decrease in neutrophil count after 1 month of SRL treatment and a high baseline serum sgp130 level independently predict clinical remission within 3 months.References[1]Nakajima T, Watanabe R, Hashimoto M, Murata K, Murakami K, Tanaka M, et al. Neutrophil count reduction 1 month after initiating tocilizumab can predict clinical remission within 1 year in rheumatoid arthritis patients. Rheumatol Int. 2021;1rin[2]Yoshikawa T, Furukawa T, Tamura M, Hashimoto T, Morimoto M, Azuma N, et al. FRI0113 THE BASELINE SOLUBLE GP130 IS ASSOCIATED WITH THE RESPONSE OF RHEUMATOID ARTHRITIS PATIENTS TO SARILUMAB. Ann Rheum Dis. 2020;79(Suppl 1):637.1-637.Disclosure of InterestsNone declared

This study evaluated the efficacy and safety of nivolumab treatment beyond progressive disease (PD) in non-small cell lung cancer (NSCLC). Medical records of consecutive patients with advanced NSCLC who received nivolumab between December 2015 and December 2018 were reviewed. Clinical outcomes of three groups of eligible patients who received nivolumab as a second-line treatment after PD were compared based on Response Evaluation Criteria in Solid Tumors v1.1. We conducted subgroup analyses in patients with and without new lesions at first PD. Twenty-eight patients continued nivolumab treatment beyond PD (TBP). Post PD, 46 patients switched to other anti-cancer treatment (OAT), and 21 received no further anti-cancer treatment (NAT). There were no significant differences in overall survival (OS) or survival post progression (SPP) between TBP and OAT groups (OS: 15.6 vs. 13.4 months, P = .40, SPP: 12.2 vs. 9.3 months, P = .42). Subgroup analyses indicated that among patients without new lesions at first PD, SPP was longer in the TBP than in the OAT groups (12.6 vs. 9.3 months, P = .22, HR: 0.64; 95% CI 0.31‒1.31). The frequency of immune-related adverse events leading to discontinuation during nivolumab beyond PD was equivalent to that for pre-PD (10.7 vs. 12.6%). No significant benefits were associated with continuation of nivolumab for advanced NSCLC patients. Continuation of nivolumab beyond PD could be a more useful option in patients without new lesions at first PD. Treatment-related toxicities require attention during nivolumab treatment not only before PD but also beyond PD.

Cardiovascular surgery is a highly invasive intervention that is often performed in elderly patients at risks of complications because of malnutrition and reduced immunity. This study investigated nutritional factors that affected length of hospital stay in patients undergoing cardiovascular surgery. Among 68 patients who underwent surgery at the Department of Cardiovascular Surgery of Gifu Municipal Hospital between April 2013 and March 2015, 55 with complete data were included in the analysis. Data on serum albumin (ALB), transferrin (Tf), pre-albumin (PA) and retinol binding protein (RBP) levels were collected. The median length of hospital stay was 29 days (stays of ≥30 days were considered long-term hospitalization). Multivariate analysis (multiple logistic regression) included age (≥ 65 years), sex (female), and ALB (≤ 3.0 g/dL), Tf (≤ 150.0 mg/dL), PA (≤ 10.0 mg/dL) and RBP (≤ 1.5 mg/dL) levels. ALB [odds ratio (OR) 10.37, 95% CI (confidence interval): 1.185-90.80

Background:Mac-2 binding protein is a cell-adhesive glycoprotein of the extracellular matrix secreted as a ligand of galectin-3 (Mac-2). Recently, a Wisteria floribunda agglutinin positive-M2BP (M2BP) assay developed using a lectin-antibody sandwich immunoassay has shown promise as a new fibrotic marker in liver fibrosis and interstitial lung disease (ILD) to detect unique fibrosis-related glycoalteration.Objectives:The aim of this study is to evaluate the utility of serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels in patients with rheumatic diseases (RD).Methods:We retrospectively measured serum M2BPGi levels in 68 patients with RD and 16 healthy controls (HC). There were no patients of cirrhosis and active hepatitis. Serum levels of M2BPGi were measured using HISCL M2BP glycosylation isomer Assay Kit. We examined the relationship between serum M2BPGi levels and clinical parameters in patients with RD.Results:In patients with RD, the median age was 62.0 years and 79.4% of them were female.Serum M2BPGi levels were significantly higher in patients with RD than in HC (median 0.98 cutoff index [COI], 0.32 COI, respectively; P < 0.00001). Patients with SLE tended to have higher serum M2BPGi levels than other rheumatic diseases.In patients with RD, a significant correlation was not found between serum M2BP levels and inflammation markers such as CRP or ferritin. However, serum M2BPGi levels were significantly correlated with B cell activation markers such as immunoglobulin free light chain and IgG (r = 0.588, 0.504) and T cell activation marker such as sIL-2R (r = 0.408).Conclusion:Most of the rheumatic diseases in this study were considered to be type I interferonopathy diseases such as rheumatoid arthritis, Sjogren’s syndrome, inflammatory myositis, scleroderma and SLE.Serum M2BPGi was reported to have a significant correlation with SLE disease activity [SS Ahn et al. Lupus. 2018; 27: 771], and also to have a significant correlation with Gakectin-9, a novel biomarker for IFN signiture [Lucas L van den Hoogen et al. Ann Rheum Dis. 2018; 77: 1810].So, it was suggested that serum M2BPGi may be a novel biomarker that indirectly indicates how much IFN is activated in rheumatic diseases.Disclosure of Interests:None declared

This paper concerns the applicability of the Weibull stress approach, instead of toughness scaling model approach, for prediction of brittle fracture initiated at defects existing at the weld terminations. Beam-to-diaphragm joint models, which were designed to represent a connection of an I-section beam to RHS column member with through diaphragms, were tested under cyclic loads. Complete joint penetration groove welds were used for the connection between the beam flange and the diaphragm. Specimens had those discontinuities at the roots of welds to the beam bottom flanges, which were created by inserting copper plates into the grooves before welding or by using wire electrical discharge machining. The prediction of brittle fracture with a variety of defect sizes by using the FE analysis was conducted. The fracture moment predicted by using the critical Weibull stress accorded with the test results of specimen with defects such as the blowhole.

Background Immune checkpoint inhibitors (ICI) have been established as a novel strategy for non-small cell lung cancer (NSCLC). However, definitive biomarkers that can predict response to ICI therapy remains established. Some prostate factors are suggested, Neutrophile-lymphocyte ratio (NLR), advanced lung cancer inflammation index (ALI), Lung Immune Prognostic Index (LIPI), then we investigate their efficiency. Methods The medical records of consecutive 296 patients with NSCLC who were treated with nivolumab at Kinki-chuo Chest Medical Center between December 17, 2015 and December 31, 2018 were collected. Nivolumab was the only ICI validated for advanced NSCLC in a second-line treatment setting. We investigated the relationship between median progression free survival (PFS) and already known prognostic factors (NLR, ALI, LIPI and so on). Results The median age was 70 (range, 40-90) years. 206 patients were male, and 224 patients were good PS group (PS 0-1). The median PFS was 3.0 months in all patients. The median PFS was 4.7 (NLR Conclusion NLR, ALI and LIPI score have the potential to be predictive factors of ICI response in NSCLC patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure A. Tamiya: Research grant / Funding (self): Taiho; Research grant / Funding (self): pfizer; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Ono pharmaceutical; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Chugai pharmaceutical; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): MSD; Research grant / Funding (self): Kissei. S. Atagi: Research grant / Funding (self): Ono pharamaceutical; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Taiho; Research grant / Funding (self): Chugai pharmaceutical; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Yakult pharmaceutical; Research grant / Funding (self): MSD. All other authors have declared no conflicts of interest.

Background Nivolumab is one of immune checkpoint inhibitors, which is reported to have efficacy in previously treated patients with advanced non-small cell lung cancer (NSCLC) in checkmate 017 / 057 / 078. It is suggested nivolumab treatment beyond progression disease (PD) may be associated with improved survival in patients with melanoma and renal cell carcinoma. However, the efficacy of beyond PD in patients with NSCLC is still unclear. Methods To evaluate the efficacy of beyond PD about nivolumab, we retrospectively reviewed the continuous patients with advanced NSCLC, who received nivolumab as 2nd line treatment in our institution between February 2016 and February 2019. The patients were eligible if they had been diagnosed PD using RECIST v1.1 by 28 February 2019. Baseline characteristics, overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), the period between RECIST v1.1 PD and clinical PD, post-PD OS, and safety were evaluated on 26 July 2019. Results Of the 144 advancer NSCLC patients treated with 2nd line nivolumab, 95 patients were eligible. Post-PD OS was 12.2 months (95% confidence interval [CI]: 5.8–26.6) in 28 patients continuing nivolumab beyond PD, 9.3 months (95% CI: 6.4–13.8) in 46 patients switching to other anti-cancer therapy, and 0.7 months (95% CI: 0.4–1.7) in 21 patients receiving no further therapy. The median period between RECIST v1.1 PD and clinical PD was 3.8 months (95% CI: 2.8–6.6) in 28 patients continuing nivolumab beyond PD. During nivolumab beyond PD, one patient died due to acute liver involvement and interstitial lung disease, one patient stopped to receive nivolumab due to grade 3 diarrhea, and one patient stopped to receive nivolumab due to grade 2 interstitial lung disease. Conclusion Post-PD OS trended to be longer in patients continuing nivolumab beyond PD than in patients switching to other anti-cancer therapy. Within the limitations of this retrospective analysis, this study suggests nivolumab treatment beyond PD may have efficacy and safety in patients with advanced NSCLC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Although inflammatory markers, such as the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and local immune markers have been shown to have prognostic utility, limited information is available regarding inflammatory and pre-existing tumour-infiltrating lymphocyte density and their association with prognosis in patients with hypopharyngeal squamous cell carcinoma. We investigated the prognostic ability of inflammatory markers and tumour-infiltrating lymphocyte density in stage III and stage IV hypopharyngeal squamous cell carcinoma patients receiving definitive treatment.Retrospective cohort study.Kurume University Hospital.Ninety-six stage III or stage IV hypopharyngeal squamous cell carcinoma patients treated at the Kurume University Hospital between 2000 and 2014.Inflammatory markers and pre-treatment tumour-infiltrating lymphocyte density were examined from recorded haematologic data and immunohistochemical analysis.Multivariate analyses showed that the CD8Higher pre-treatment CD8

A number of beam-to-RHS column connections with various weld defects are modeled numerically. The weld defects are the same as those observed during the Kobe Earthquake and in the past full-scale tests. Focusing on fractures from weld defects, a procedure to evaluate fracture moments of beam-to-column connections is proposed based on a series of numerical analyses. Matrices showing the fracture moments as a function of the size and location of weld defects and the material toughness are presented. In addition, the rotation capacity of the beams in the beam-to-column assemblies is presented based on the past extensive test results and FE analyses.

Brittle fractures in steel can have devastating effects during its use, such as the collapse of buildings during earthquakes. This paper describes the effects of cyclic loading on the occurrence of brittle fracture and presents a brittle fracture prediction method. Notched specimens of steels with low and high fracture toughness were tested under monotonic and cyclic loading. A cumulative ductility estimation method was developed to predict the occurrence of brittle fracture using the Coffin–Manson law and Miner's rule. This method is based on the empirical relationship between the ductility amplitude or Weibull stress and the number of cycles at brittle fracture. Cumulative damage theory was also used to consider different cyclic amplitudes. The proposed approach can be employed to predict cumulative ductility at brittle fracture and showed a relatively high correlation coefficient between the calculated and experimental results. In addition, this approach can be used to predict brittle fracture using data from samples with different toughness and notch shapes in a unified manner, unlike many previous methods.

Objective:Superoxide anions are recognized as mediators of intracellular signaling cascades and are known to participate in cardiovascular diseases such as arteriosclerosis and hypertension. Previous studies reported that the production of superoxide is modulated by many factors including Ang II - A

Lentogenic Newcastle disease viruses (NDVs), circulating among waterfowl, have the potential to become highly pathogenic by replication in chickens. The pathological studies that compare NDV infections in chickens and waterfowl are rare. The virulent 9a5b mutant NDV isolate was generated by passaging the lentogenic Goose/Alaska/415/91 NDV isolate in chickens. The pathogenesis of the virulent 9a5b mutant isolate is unknown in both chickens and waterfowl. In this study, the virulent 9a5b mutant NDV isolate was inoculated intranasally in 32-day-old specific pathogen-free white Leghorn chickens and Japanese commercial ducks. Unlike ducks, which remained clinically normal throughout the study, chickens had depression, gasping, oral discharges, and greenish-white soft feces. Gross and histologic lesion patterns as well as viral replication supported the differing clinical outcome. Ducks had slight inflammation mainly in respiratory and digestive tracts, whereas slight nonpurulent encephalitis, necrotizing pancreatitis, tubulointerstitial nephritis, and mild inflammation in respiratory and digestive tracts were detected in chickens. In agreement, interferon-beta (IFN-β)–immunopositive signals were more intense in lung tissue of ducks than that of chickens, and NDV replications were detected intensively in chicken tissues. These results suggest that the 9a5b mutant NDV isolate is more virulent in chickens, and slight histological lesions were induced in ducks even with virulent NDVs.

It is well-known that a reduction in thicknesses of soft magnetic materials is one of effective methods to reduce an eddy current loss, and soft magnetic thin ribbons are widely used for high-frequency driven electric machines. Typical soft magnetic thin ribbons are produced by rapid quenching methods, and their thicknesses are approximately 20 $\mu \text{m}$ . In present study, we proposed a novel fabrication method of soft magnetic thin ribbons $( using an electroplating method, and evaluated the ac magnetic properties of the thin ribbons.

Recently, we have reported Fe-Ni films electroplated in Deep-Eutectic-Solvent-based plating bath, and confirmed that the DES-based bath shows high current efficiency (> 90 %) [1]. In our previous studies, we did not use any additives for improvement in levelling and brightness of the films. As studies on additives in DES-based baths are not enough, we focus on phenanthroline, which is used as complex agent [2]–[3], as an additive. In this study, we investigated the effect of the phenanthroline compounds to improve surface roughness and soft magnetic properties.

Fe-Ni-Co ternary alloys are attractive soft magnetic materials, and we have reported a flux gate sensor with an electroplated Fe-Ni-Co film [1]. For improvement in robustness of the sensor output against the temperature variation, an increase in Co content of the film are effective since the Curie temperature increases with increasing the Co content. In the present study, we electroplated Fe-Ni-Co films focusing on the Co content, and evaluated the magnetic and the structural properties.

Deep Eutectic Solvents (DES) are expected as a new solution for plating bath. It is well-known that the bath temperature is one of dominant factors to determine film properties such as surface roughness and magnetic properties. In order to investigate the effect of the bath temperature on film properties, we plated Fe 22 Ni 78 films in the DES-based baths with various temperatures.

Recently, we reported magnetic Fe films plated in Deep-Eutectic-Solvent-based plating baths, and clarified that a DES is one of attractive solvents due to high plating rate (approx. $120 \mu \text{m}/\text{h}$ ) and high current efficiency (> 90 %) [1]. In order to further increase the plating rate, we focused on the current density during the plating. In the present study, we investigated the effect of the current density on plating rate, magnetic properties and surface roughness of the Fe film.

The iliac muscle is an important skeletal muscle related to ambulatory function. The muscles related to ambulatory function are the psoas major and iliac muscles, collectively defined as the iliopsoas muscle. We have proposed an automated recognition method of the iliac muscle. Muscle fibers of the iliac muscle have a characteristic running pattern. Therefore, we used 20 cases from a training database to model the movement of the muscle fibers of the iliac muscle. In the recognition process, the existing position of the iliac muscle was estimated by applying the muscle fiber model. To generate an approximation mask by using a muscle fiber model, a candidate region of the iliac muscle was obtained. Finally, the muscle region was identified by using values from the gray value and boundary information. The experiments were performed by using the 20 cases without abnormalities in the skeletal muscle for modeling. The recognition result in five cases obtained a 76.9% average concordance rate. In the visual evaluation, overextraction of other organs was not observed in 85% of the cases. Therefore, the proposed method is considered to be effective in the recognition of the initial region of the iliac muscle. In the future, we will integrate the recognition method of the psoas major muscle in developing an analytical technique for the iliopsoas area. Furthermore, development of a sophisticated muscle function analysis method is necessary.

Proximal femoral bone mineral density (BMD) can be measured by dual energy X-ray absorptiometry method in the neck, trochanter, intertrochanter, total and Ward's triangle area. Ward's triangle area of the proximal femur is a smaller area to measure than the others, and the position varies, depending on the status of inner rotation of the target leg. In this study, the measurements of the proximal femoral BMD in women were carried out on the neck, trochanter, intertrochanter, total and Ward's triangle area with the, subjects' legs turned 15 degrees toward the inside. The Ward's BMD were measured using Ward's cognitive method, in which the measured BMD were compared among age groups of 50-59, 60-69, 70-79 and 80-89 to determine whether this process could reveal decreased femoral BMD in elderly women. The correlation between BMD and age was tested using the Pearson correlation coefficient. In all measured parts, the BMD of women age 50-59 were significantly higher than those of women age 80-89. The correlations between BMD and age were negative in all measured parts, and the most negative correlation was between age and Ward's BMD. The study using Ward's cognitive method showed an inverse correlation between Ward's BMD and age in women.

K. Yamashiro, M. Tagami, K. Azuma, A. Nakamura, O. Kato, K. Taira, M. Azuma, H. Takeda and H. Suzuki Cytodiagnosis through use of a z-axis video by volunteer observers: a promising tool for external quality assessment Objective: This study examined whether cytological diagnosis through the use of a video, which shows the changing depth of focus in the microscopic field, described as a z-axis video, is useful compared with a still image. Methods: From 17 cytology preparations of fine needle aspiration of the breast, we made six z-axis videos per case. A frame exhibiting the characteristic features was then extracted from each video and saved as a representative still image. One hundred and twenty-eight volunteer cytotechnologists were randomly divided into two groups of video observers and still image observers. The participants were asked to make a diagnosis of benign, indeterminate, suspicious or malignant without having any clinical information other than the age of the patient. Diagnoses were categorized as ‘recommended’ or ‘unacceptable’ according to degree of correlation with histology. Results: The number of definitive diagnoses of ‘benign’ or ‘malignant’ were increased in video observers, and indeterminate or suspicious categories were decreased (P = 0.013). The distribution of diagnostic categories in three of the 17 cases was significantly different; the distribution in the remaining cases was similar between the two groups. The z-axis video observers may have selected the definite diagnoses with confidence because they observed valuable microscopic findings by ‘focusing through observation’. The average number of ‘recommended’ diagnoses by individual observers was significantly higher in the video observer group than in the still image observer group (P = 0.016). In contrast, the average number of ‘unacceptable’ diagnoses was significantly lower (P = 0.019). Conclusions: A z-axis video is easy to obtain and is therefore expected to become a powerful diagnostic modality for the external quality assessment of clinical cytology and even in the field of primary cytodiagnosis.

We compare the mutual interactions between the top-and bottom-gate fields in a dual-gate structure for amorphous InGaZnO4 (a-IGZO) and hydrogenated amorphous silicon (a-Si:H) thin-film transistors (TFTs). We find that a-IGZO TFTs show more significant mutual interactions than a-Si:H TFTs. By using a wide variety of a-IGZO TFTs with varying thicknesses of a-IGZO and gate-insulator layers, we have investigated, on the basis of a conventional fully depleted n-channel silicon-on-insulator model, the mechanism behind parallel shifts in transfer characteristics caused by negative top-gate voltages. Experimental results, even for relatively thick (over 150 nm) a-IGZO layers, are in good agreement with the fully depleted model. This fact may be related to the nonexistence of hole accumulation in a-IGZO, which is an intrinsic property of oxide semiconductors. In contrast, for the a-Si:H TFTs, there is a considerable discrepancy between the experimental results and the model. This discrepancy probably results from the limited penetration of band bending into the a-Si:H layer, as well as from the hole accumulation at the top interface. Such analysis of a-IGZO TFTs is of practical importance in device applications because many issues related to the fabrication and structure of a-IGZO TFTs may be resolved with a better understanding of dual-gate performance.

Recent studies have shown that bone marrow transplantation reduces hyperglycaemia in a mouse model of diabetes induced by streptozotocin. However, the essential factors for the improvement of hyperglycaemia by bone marrow transplantation have not been fully elucidated. The aim of this study was to search for such factors.We investigated the effect of irradiation to whole body, to abdomen alone or to whole body excluding abdomen, followed by infusion or no infusion of bone marrow cells. We also investigated the effect of bone marrow transplantation on beta cell-specific vascular endothelial growth factor-A gene (Vegfa) knockout mice.Bone marrow transplantation improved streptozotocin-induced hyperglycaemia and partially restored islet mass. This change was associated with increased islet vascularisation. Among the other methods investigated, low-dose irradiation of the whole body without infusion of bone marrow cells also improved blood glucose level. In streptozotocin-treated beta cell-specific Vegfa knockout mice, which exhibit impaired islet vascularisation, bone marrow transplantation neither improved hyperglycaemia, relative beta cell mass nor islet vascularisation.Our results indicate that whole body irradiation is essential and sufficient for restoration of beta cell mass after streptozotocin treatment independent of infusion of bone marrow cells. Vascular endothelial growth factor-A produced in beta cells is also essential for this phenomenon.

Based on the phase-modulated excimer laser annealing method, an advanced crystallization technology called the “pseudo-single-nucleus lateral crystallization method” has been reported recently. Arrays of large rectangular Si grains of almost 6 μm × 5 μm in size were successfully grown by the new method with a sufficiently wide process window. The characterization of crystallized film was investigated by electron backscattering pattern (EBSP) method, Raman spectra and AFM, and it was confirmed that the two-dimensionally large Si grain had a good crystallinity. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Ectopic activation of hedgehog (HH) signalling in pancreas induces various abnormal morphogenetic events in the pancreas. This study analysed the dose-dependent requirement of patched homologue 1 (PTCH1), a negative regulator of HH signalling on pancreatic development. We used a recessive spontaneous mutant mouse denoted as mes which carries a mutated Ptch1 resulting in deletion of the most carboxy-terminal cytoplasmic domain of the PTCH1 protein. In this study, we analysed pancreatic morphology in Ptch1 +/+ , Ptch1 +/mes , Ptch1 +/−, Ptch1 mes/me s and Ptch1 −/mes mouse embryos, as well as the islet mass in adult Ptch1 +/+, Ptch1 +/mes and Ptch1 +/− mice. Until embryonic day (E) 12.5, no obvious abnormality of pancreas was observed in any of the Ptch1 mutants. The levels of PDX1 and glucagon were also not evidently different among the mice genotypes studied. Thereafter, morphological abnormalities appeared in the Ptch1 mutant mice. The beta, alpha and exocrine cell masses decreased at E18.5 in parallel with increased HH signalling, with beta cell mass showing the highest sensitivity to HH signalling with a significant decrease even in Ptch1 +/mes mice. Adult Ptch1 +/− mice also showed a significant decrease in beta cell mass compared with wild-type mice. Our findings indicate that the carboxy-terminal domain of Ptch1 is essential for pancreatic development. In addition, the loss of Ptch1 function decreases both the endocrine and exocrine cell mass in a dose-dependent manner, with beta cells particularly sensitive to changes in HH signalling.

We report a novel method to construct a two-dimensional network of gold nanoparticles and metal complex molecules. Terpyridine derivatives having a thiol group are adsorbed on a gold nanoparticle surface through formation of a gold-sulfur bond. A monolayer of nanoparticles is then formed on the water surface, then transferred onto a Si/SiO 2 substrate. The introduction of Fe 2+ from a Fe(BF 4 ) 2 solution forms an iron(II) bis(terpyridine) complex, which simultaneously forms a network where the complex molecules interlink adjacent nanoparticles. The conductivity of the network, formed by the conjugated terpyridine derivative, is 4 or 5 orders of magnitude higher than that of non-conjugated derivatives. Conductivity is modulated by gate voltage when a conjugated derivative is used but not when a non-conjugated derivative is used.

Characteristics of combustion control with direct methanol injection in homogeneous charge compression ignition (HCCI) combustion were investigated over a wide operating range under several conditions including different compression ratios and three main fuels with different octane numbers. The operating range of HCCI combustion is limited by knocking at one extreme and misfire at the other. On the knocking side, moderate methanol injection is shown to be effective at preventing knock. In addition, a lower compression ratio can delay the onset of both low- and high-temperature oxidations and suppress rapid combustion due to the lower in-cylinder gas temperature while not directly affecting the quantity of heat released during low-temperature oxidation. To extend the misfire limit, a lower octane number fuel yields a greater low-temperature heat release, increasing the temperature in the interval between the low- and high-temperature oxidation, which prevents misfiring. Therefore, a combination of lower compression ratio and lower octane number fuel assisted by a direct methanol injection can expand the operating load range envelope as the low-temperature oxidation can be controlled flexibly by varying the quantity of methanol injection with the operating condition. It was concluded that the ignition suppression effect of methanol in HCCI combustion is much stronger than those of other fuels with a similar octane number.