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Signal disruptions in small animals during the realization of the Forced Oscillation Technique are a well-known cause of data loss as it leads to non-reliable estimations of the respiratory impedance. In this work, we assessed the effects of removing the disrupted epoch when a 3-seconds input signal composed of one and a half 2-seconds full cycle is used.We tested our hypothesis in 25 SAMR1 mice under different levels of bronchoconstriction due to methacholine administration by iv bolus injections in different doses (15 animals) and by iv continuous infusion in different infusion rates (10 animals). Signal disruptions were computationally simulated as sharp drops in the pressure signal within a short timescale, and signal processing was performed using own developed algorithms.We found that the model goodness of fit worsens when averaging techniques to estimate the input respiratory impedance are not used. However, no statistically significant differences were observed in the comparison between Constant Phase Model parameters of the full 3-s signal and the 2-s non disrupted epoch in all doses or infusion rates for both methacholine delivery strategies.The proposed technique presents reliable outcomes that can reduce animal use in Forced Oscillation Technique realization.

In both 5- and 15-min data, FI was significantly higher in malignant tissues than in benign tissues. The diagnostic accuracy was similar at 5 and 15 min. Therefore, the 5-min FI was enough applying in the further analyses.

In a solution of the copolymer, P(EHMA-APMA), consisting of ethylhexyl methacrylate (EHMA) and the photo-responsive azopyridine methacrylate (APMA), the E form of APMA showed photo-reversible isomerization to the Z form upon UV irradiation. After addition of the cobalt(II) Schiff base (CoS), the copolymer complex, P(EHMA-(E)-APMA)-CoS, was produced, and the (E)-APMA moieties coordinated to CoS no longer underwent photo-induced isomerization. The complexation-sensitive isomerization of (E)-APMA had a large extinction coefficient and the apparent equilibrium constant (Kapp) for the coordination reaction of (E)-APMA with CoS in a dilute solution was calculated to be 4.4 × 104 M−1 ([APMA moiety] = 0.05 mM) and 1.0 × 105 M−1 ([APMA moiety] = 0.003 mM) at 25 °C. The resulting concentration-dependent large Kapp values were due mainly to a micro-heterogeneous solution environment, consisting of a micro-suspension with a large solvent phase and a small polymer-domain phase caused by the extreme dilution, in addition to the thermodynamic stabilization of the five-coordinate CoS via the local concentration effect of the coordinating polymeric APMA ligands located only in the polymer domain.

Snoring is a problem that affects a large part of the population and is usually associated with or indicative of other diseases, several of them are linked to sleep disorders such as apnea. Tools that automatically identify snoring, providing information to the patient and to the medical professional are very useful since it is possible to identify the problem and follow the progress of someone undergoing anti-snoring treatment. One of the tasks that this tool must perform is the identification of sound events. One technique that can be used for this involves the use of an adaptive threshold over a predefined length of the audio itself. This paper aimed to identify the behavior of the sound events identification (snoring and non-snoring) by varying the length of the audio chosen to calculate the threshold. When using small windows, a large number of events are detected. This value drops exponentially by increasing the size of the window until it reaches a plateau. Furthermore, not only the number of events that are not snoring are impact, but even the number of real snoring, which leads to the loss of the solution’s sensitivity., XII SIMPÓSIO DE ENGENHARIA BIOMÉDICA - IX SIMPÓSIO DE INSTRUMENTAÇÃO E IMAGENS MÉDICAS

Hyperuricemia is closely associated with insulin resistance. Xanthine oxidoreductase (XOR), a key enzyme known to catalyze purines to uric acid, is expressed in ubiquitous tissues. In addition, XOR expression is upregulated in obesity. Therefore, we speculated that XOR may exacerbate insulin resistance. But, the effects of XOR on insulin sensitivity have not been fully elucidated. Febuxostat is a selective XOR inhibitor. In this study we investigated the effect of suppression of XOR using febuxostat on insulin sensitivity in vivo and in vitro. Male Wistar rats were fed with 60% high fat diet containing with either febuxostat or not, for 4 weeks. Euglycemic-hyperinsulinemic clamp studies were performed after an 8-h fast. Differentiated C2C12 cells were incubated with 0 or 10 μM febuxostat. For Xor silencing experiments, we used the Xor RNAi adenovirus. The glucose infusion rate and insulin stimulated-glucose disposal rate were significantly increased by 12% (P In conclusion, our findings demonstrated that suppression of XOR had beneficial effects on skeletal muscle insulin sensitivity in an insulin resistant state. The upregulation of XOR in skeletal muscle might cause the insulin resistance. Disclosure C.T. Moriya: None. H. Satoh: None. S. Kakehi: None. H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited.

We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand,Xdhexpression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereasXdhexpression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreasedXdhexpression in 3T3-L1 adipocytes. DPP-4 treatment significantly increasedXdhexpression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreasedXdhmRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressingXdhexpression in epididymal adipose tissue of obese subjects.

Hyperuricemia is closely associated with various metabolic disorders such as diabetes, hypertension, dyslipidemia, and cardiovascular diseases. Xanthine oxidoreductase (XOR) is a key enzyme known to catalyze purines to uric acid. Febuxostat is an orally-active, potent, non-purine, selective XOR inhibitor. However, the effect of febuxostat on glucose and insulin metabolism has not been fully elucidated. Therefore, we investigated the effect of febuxostat on insulin sensitivity in male Wistar rats. Insulin sensitivity was evaluated by the hyperinsulinemic-euglycemic glucose clamp studies (at 25 mU/kg/min insulin infusion rate) after an 8-hour fast. Male Wistar rats were 60% high fat diet containing with either febuxostat (∼4 mg/kg/day) or not, for 4 weeks. The glucose infusion rate and insulin-stimulated glucose disposal rate were significantly increased by 12% and 17%, respectively. But hepatic glucose output was no significant change between two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt and AMPK were significantly increased by 90% and 53%, respectively, only in skeletal muscle of febuxostat treated rats. Next, to investigate whether this effect is direct or indirect, we examined the effect of febuxostat in the differentiated C2C12 cells. The treatment of 10 μM febuxostat for 48 hours significantly increased the phosphorylation of Akt and AMPK by 65% (P=0.017) and 43% (P=0.028) in the differentiated C2C12 cells, respectively. These results suggest that this effect of febuxostat is direct. In conclusion, these findings indicate the possibility that febuxostat acts directly on the skeletal muscle and improves insulin resistance. Disclosure C.T. Moriya: None. H. Satoh: None. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.

While it has been reported that G0/G1 switch gene 2 (G0S2) inhibited the lipolytic activity of adipose triglyceride lipase, previously, we demonstrated that hepatic G0S2 promotes hepatic insulin resistance by the exacerbation of hepatic steatosis in the high fat diet (HF) fed male Wistar rats. However, the physiological role of hepatic G0S2 is still unknown. Estrogen suppresses gluconeogenesis and de novo lipogenesis in the liver and a decrease in serum estrogen levels in menopause is closely associated with the insulin resistance. These findings indicated that postmenopausal hepatic steatosis and insulin resistance are strongly associated with reductions in estrogen levels. To investigate the involvement of hepatic G0S2 in postmenopausal insulin resistance, we studied the effect of G0S2 on insulin sensitivity in HF-fed ovariectomized female Wistar rats by overexpressing G0S2 protein using an adenovirus (Ad). Six weeks female Wistar rats were ovariectomized (OVX) or sham operated (OVI), and maintained on 60% HF for a total of 8 weeks. Ad-G0S2 or control Ad-GFP were injected to these rats after 7 weeks diet challenge. On day 7 post Ad injection, euglycemic-hyperinsulinemic clamp studies were performed after a 12-hour fast. During the clamp studies on the OVI rats, the glucose infusion rate (Ginf), the insulin stimulated glucose disposal rate (IS-GDR), and the insulin suppression of HGO were not significantly different between the G0S2 and GFP groups. On the other hand, the OVX-G0S2 rats exhibited increased clamp HGO (∼36%) and decreased suppression of HGO (∼43%) but no significant change in ISGDR compared to OVX-GFP rats. Consist with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly decreased only in the liver of OVX-G0S2 rats. In conclusion, hepatic G0S2 exacerbates hepatic insulin resistance only in the estrogen deficient status. The expression level of hepatic G0S2 could affect the development of hepatic insulin resistance in the postmenopausal stage. Disclosure H. Satoh: None. Y. Sugaya: None. C.T. Moriya: None. T. Miyatsuka: Research Support; Self; Eli Lilly and Company, Japan Society for the Promotion of Science, Daiichi Sankyo Company, Limited, Novartis Pharma K.K., Astellas Pharma Inc., MSD K.K., Takeda Pharmaceutical Company Limited. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.

O objetivo desse artigo é apresentar experiências de formação docente no Ensino Superior, no âmbito do Programa Graduação Inovadora da UNESP. Para atender a demanda de formação docente na universidade, o programa tem como objetivo contribuir para o desenvolvimento de estratégias inovadoras. De 2015 a 2016, foram ofertados cinco cursos com tutoria para os docentes da UNESP, discentes de pós-graduação e corpo técnico. Por meio de uma análise quanti-qualitativa observou-se que a formação continuada do professor da Educação Superior pode suscitar uma perspectiva de transformação na prática docente e a mudança da visão dos envolvidos no processo ensino e aprendizagem. Em 2017, pretende-se dar continuidade à análise dos dados registrados no Ambiente Virtual de Aprendizagem (AVA) no intuito de consolidar um amplo estudo sobre a construção de uma cultura de inovação na Educação Superior.Palavras-chave: Inovação. Ensino superior. Formação de professores.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients’ outcomes.

To cite this article: Hosoya K, Satoh T, Yamamoto Y, Saeki K, Igawa K, Okano M, Moriya T, Imamura O, Nemoto Y, Yokozeki H. Gene silencing of STAT6 with siRNA ameliorates contact hypersensitivity and allergic rhinitis. Allergy 2011; 66: 124–131. Abstract Background: Silencing of genes using small interfering RNA (siRNA) is a recently developed strategy to regulate the synthesis of target molecules. Signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity. Methods: To elucidate the therapeutic potential of using siRNA to inhibit STAT6 in allergic reactions, we determined the nucleotide sequences of siRNA specific for STAT6. Results: The selected sequences of STAT6 siRNA specifically inhibited the generation of STAT6 synthesis in dermal fibroblasts and eotaxin (CCL11) production in response to IL-4/TNF-αin vitro. Local administration of STAT6 siRNA in vivo alleviated contact hypersensitivity responses to chemical haptens. This was accompanied by reduced local production of IL-4, IL-13, eotaxin (CCL11), TARC (CCL17) and MDC (CCL22). Similarly, consecutive intranasal instillation of STAT6 siRNA markedly inhibited inflammatory cellular infiltration of mucosal tissues in allergic rhinitis responses in association with reduced IL-4 and IL-5 production from regional lymph node cells. Immediate responses, such as sneezing and nasal rubbing behaviors, were also improved by STAT6 siRNA. Conclusions: Local administration of STAT6 siRNA is thus a promising therapeutic strategy for both Th2-mediated cutaneous diseases and allergic rhinitis.

As awareness of next-generation networks in the telecommunications industry increases, the possibilities of novel services for integrating web applications in the Internet and new IP-based telecommunication networks are gaining attention. However, the industry is still seeking an ideal application programming interface design to publish telecommunication functions with web service technology. The industry is also unsure whether supplying not only APIs but SDKs is really necessary, even though there is a vague consensus that SDKs enable programmers to create novel web-telecom applications. Therefore, we conducted a quantitative experiment with human participants to investigate the productivity of web-telecom application programming with Parlay X and an SDK. From the results, we discuss the inevitable problem that web-telecom APIs and SDKs, in handling stateful and asynchronous communication with web service technologies, confuse programmers.

The use of diffractive optics having surface appearance like diffraction grating or Fresnel lens, which consist of a number of microgrooves with various shapes is analyzed. One of them is flat-end microgrooves having no slope at the end. The existence of a slope limits the design of microgrooves and causes unnecessary diffraction of light and losses. Thus, the slope must be eliminated. The study deals with the creation of curved V-shaped microgrooves with two flat-ends on a curved surface by using 6-axis control non-rotational cutting tools. The proposed method shows the effectiveness in creating flat-ended curved microgrooves on curved surfaces.

The aetiology of ulcerative colitis is inadequately understood, and drug therapy has been empirical rather than based on sound understanding of disease aetiology. This has been a major factor for refractoriness and adverse drug effects as additional complications. However, ulcerative colitis by its very nature is exacerbated and perpetuated by inflammatory cytokines, which are released by peripheral granulocytes and monocytes as well. Additionally, active ulcerative colitis is often associated with elevated peripheral granulocytes and monocytes with activation behaviour and are found in vast numbers within the colonic mucosa. Hence, from the clinicopathologic viewpoint, granulocytes and monocytes are appropriate targets for therapy in ulcerative colitis. Based on this thinking, an Adacolumn has been developed for depleting excess granulocytes and monocytes by adsorption.By colonoscopy, biopsy and histology, we investigated the impact of granulocyte and monocyte adsorption (GMA) on the mucosal level of granulocytes and monocytes in patients with active ulcerative colitis. Forty-five patients (26 steroid naïve and 19 steroid-dependent), mean age 44.7 yr, were included. Twenty patients had total colitis and 25 had left-sided colitis. Each patient was given up to 11 GMA sessions over 12 weeks. No patient received additional medications within 4 weeks (steroid) to 8 weeks (other immunosuppressants) prior to entry or during the GMA course. Colonoscopy together with biopsy was done at entry and within 2 weeks after the last GMA session.At entry, the mean clinical activity index was 12.6; range 10-16. A total of 400 colonic biopsies were examined, which revealed massive infiltration of the colonic mucosa by granulocytes, and GMA was associated with striking reduction of granulocytes in the mucosa. At week 12, 33 of 45 patients (73.3%, P0.01) had achieved clinical remission (the mean clinical activity indexor= 4). Colonoscopy revealed that most non-responders had deep colonic ulcers and extensive loss of the mucosal tissue. The response rate in steroid naïve subgroup was 22 of 26 patients (84.6%, P0.005) and in steroid-dependent was 11 of 19 (57.9%, P0.05 and P=0.02154 for steroid naïve vs. steroid-dependent). Patients who achieved remission could continue with their salicylates. On average, remission was sustained for 7.8 months in all 33 responders.This is the first report showing a striking difference in clinical response to GMA between steroid naïve and steroid-dependent patients. Further, patients with deep colonic ulcers together with extensive loss of the mucosal tissue are not like to respond to GMA.

Even with the standard first-line chemotherapy, advanced non-small cell lung cancer (NSCLC) recurs in most cases. The purpose of this study is to develop a new chemotherapeutic regimen for patients with NSCLC that has relapsed or was refractory to previous chemotherapy. Patients with proven NSCLC refractory or recurrent after previous single-regimen chemotherapy, PS of 0-2, age of 15 years or older, adequate organ functions and measurable lesions were treated with irinotecan at 60 mg/m(2) and cisplatin at 25 mg/m(2) with 1000 ml hydration on day 1. This administration, considered as one cycle, was repeated every week without rest unless encountering defined skip and dose-reduction criteria. The treatment was administered for six cycles over a 49-day period, both median values, to 48 patients, with a response rate of 26%, progression free and median survival times of 3 and 11 months, respectively, and a 1-year survival rate of 46%. The most frequent grade 3 or 4 toxicities were neutropenia, anaemia and nausea, which were manageable. Subset analyses suggested that the response rate was independent of response to the first-line chemotherapy. In conclusion, second-line chemotherapy of weekly irinotecan and cisplatin with minimum hydration seemed effective, with tolerable toxicity, and is potentially useful irrespective of the outcome of previous chemotherapy.

Small animals such as mice are generally used in experiments that study the behavior of the respiratory system under the influence of drugs, and accurate gas flow measurements are necessary due to the small volumes involved. Based on this need, a mechanical ventilator for small animals was developed using a linear actuator coupled with a 3ml precision glass syringe controlled by a driver. A mechanical load representing a mouse’s respiratory system consisting of a rigid plastic cylinder with internal volume of 78ml was ventilated by the machine, and its measured resistance and elastance parameters were compared to values obtained with theoretical mathematical models. A 12.7% maximum deviation was found in the model’s elastance in comparison with the predicted value, and the measured resistance did not assume the expected behavior of a linear system, decreasing sharply with the increase of frequency.

Respiratory impedance provides us a consider-able amount of information about respiratory diseases and is an important tool in medical diagnosis. One useful technique for determining the respiratory impedance is the Forced Oscil-lation Technique (FOT), consisting in applying a known flow or volume signal in the study component and measuring its resulting pressure. Our interest is in the wavetube method, which consists of using a loudspeaker to generate the oscillato-ry known signal. This speaker is attached to a rigid circular tube, which is then connected to the element that we want to calculate the impedance. To perform this calculation, there are pressure signals, which are acquired with pressure transduc-ers. In this article we focus on developing a bandpass speaker box for the realization of the oscillations for the wavetube method. Based on an absence in studies about the pressure generator for the wavetube method, we compared the bandpass box with a vented box. We conducted a computer simulation of the amplitude response of each box and then collect experimental data of pressure signals generated from each speaker to perform the comparison between the ampli-tude responses generated by each box. We concluded that the use of a bandpass speaker is an interesting alternative for the realization of the FOT. However, the use of a vented speaker box is not totally invalid, as predicted by the computer simula-tions.

We have synthesized various main-chain fluorinated polymers and studied base-resin properties, such as transparency at 157 nm, solubility in a standard alkaline developer, and lithographic performance. Main-chain-fluorinated polymers were synthesized by copolymerization of tetrafluoroethylene (TFE) with cyclic monomers, especially newly synthesized norbornene derivatives. We studied the correlation between pKa(OH) and the solubility of the copolymers of TFE and functional (fluoroalkyl alcohol group) norbornenes. Their solubility depends on the pKa value of the fluoroalkyl alcohol groups. We studied the impact of the polymerization initiators on base-resin properties. High transparency was obtained by using the fluorocarbon initiator. It was also confirmed that the monocyclic component improves dry-etch resistance and that fluorination at the terminal groups improves alkaline solubility. In addition, we found that the development characteristics of TFE/norbornene copolymers were significantly improved by the stereoselective (endo versus exo) partial protection of the hydroxyl groups in the fluoroalkyl alcohol moiety attached to norbornene unit. The polymer protected only in the exo position of the norbornene unit in the copolymer had a higher Rmax and a higher contrast. Positive-working resists based on these fluoropolymers were developed and 55 nm dense lines could be delineated by exposure at 157 nm wavelength with an alternating phase shift mask on a 0.9 NA 157 nm exposure tool.

Main-chain-fluorinated base-resins, using the copolymer of tetrafluoroethylene and functional (hexafluoroisopropanol (HFA) group) norbornene, were synthesized. Partial protection of its hydroxyl group as ethoxymethyl group was achieved by two methods, by copolymerization (Method A) or by polymer reaction (Method B). The partial protection by copolymerization was conducted by copolymerizing TFE with the mixture of protected and unprotected monomers (Method A, copolymerization). The partial protection was also carried out by reacting hydroxyl group of the polymer, which is composed of TFE and unprotected monomers with ethoxymethyl chloride in the presence of an amine (Method B). In the polymer reaction, only exo position of the norbornene unit was protected. Their fundamental properties, such as transparency at 157 nm and solubility in a standard alkaline developer, were characterized and studied. A high transparency, i.e., absorbance of less than 0.4 µm -1 , was achieved in both methods. However, the polymer prepared by the polymer reaction (Method B) was deprotected more quickly. And this polymer had a higher dissolution rate and development contrast than the polymer prepared by copolymerization (Method A). The Positive-working resists based on this fluororesins were developed and 55 nm dense lines could be delineated by the exposure at 157 nm wavelength with alternating phase shift mask on a 0.9 NA 157 nm exposure tool. Keywords: 157-nm lithography, resist, fluoropolymer, tetrafluoroethylene, norbornene, exo, polymer reaction

Tetrafluoroethylene-based copolymers with functional norbornenes were synthesized and their fundamental properties, such as transparency at 157 nm and solubility in a standard alkaline developer, were characterized. A high transparency, i.e., absorbance of less than 0.5 μm-1, was achieved by optimizing the polymerization conditions with a variety of functional norbornene monomers. Positive-working resists formulated by the fluororesins were developed and showed good transparency of less than 1 μm-1 at 157 nm, and good developability without any swelling behavior in a standard alkaline solution of 0.26-N tetramethylammonium hydroxide, and an acceptable dry-etching resistance as good as ArF resists. And fine patterns of 65-nm dense lines and spaces could be delineated by the exposure at 157-nm wavelength.

1. Histological and histochemical profiles of Musculus pectoralis (PT, type IIB fibres), M. iliotibialis lateralis (ITL, types IIA + IIB fibres) and M. puboischiofemoralis pars medialis (PIF, type I fibres) were compared in carbon dioxide (37%, 70 s) and electrically (14 V, 5 s) stunned male chickens. 2. Muscle materials were taken at 0, 4 and 24 h from carcases dressed and cooled with ice-water mixture for 30 min. Glycogen and fat contents, and adenosine triphosphatase and reduced nicotinamide adenine dinucleotide dehydrogenase activities of fibres were measured. 3. In PT muscle at 0 h, gas stunned chickens showed many fibres with high glycogen content but those electrically stunned contained few such fibres. Fibres from gas stunned birds had lost almost all their glycogen after 24 h of cold storage. 4. In the ITL muscle of gas stunned chickens at 0 h residual glycogen was observed in type IIB fibres. In contrast, in the electrically stunned birds it was in type IIA, showing the different effects of the stunning methods. During cold storage, glycogen disappeared earlier in type IIB than IIA fibres. 5. In PIF muscle with fibres of low glycogen content, the gas stunned chickens maintained a good fibre structure for 4 h or more, but the electrically stunned had already lost intact fibre structure at 4 h. 6. These results indicated that the carbon dioxide stunning was a better method for chicken welfare and meat quality than electrical stunning.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) accompanied with hypoxaemia may induce net protein catabolism and hypoxaemia could be an important trigger of a systemic catabolic response. The aim of this study was to examine the anabolic effects of recombinant human insulin-like growth factor-I (IGF-1) in rats exposed to hypoxia. Although acute hypoxia is usually accompanied with a decrease in dietary intake, the usual nitrogen intake was maintained in this study. Sprague-Dawley rats were maintained by continuous infusion of solution for total parenteral nutrition for 6 days. The animals were then randomly assigned to a normoxic (N) or a hypoxic (H) group. During the last 3 days of the experiment N and H rats were randomised to receive either IGF-I or vehicle. Exposure to hypoxia caused a decrease in body-weight gain accompanied by a negative nitrogen balance, which was mainly due to increased urinary nitrogen excretion. No effect of recombinant human IGF-I treatment on body weight was observed during exposure to hypoxia, although nitrogen balance normalised. The co-infusion of recombinant human insulin-like growth factor-1 and total parenteral nutrition has a significant net anabolic effect, as demonstrated by nitrogen retention and reduction in urine protein excretion observed in rats. Insulin-like growth factor-1 may help to ameliorate the protein catabolism observed under hypoxic conditions.

This article describes Honda’s concept for fuel cell vehicle development and the positioning of fuel cell vehicles compared with various power plant types, as well as the recent development status, features and issues for fuel cell vehicles.

Oxidation behavior of a series of Cu–Ta alloys prepared by co-deposition of RF sputtered pure copper and tantalum was studied in air. Alloy composition, oxidation temperature and relative humidity (RH) ranges examined were 5–69 at.% Ta (alloys with 22–69 at.% Ta were amorphous), 40–85°C and 20–70%, respectively. Although Cu–58at.%Ta alloy showed no apparent change, some of the alloys exposed to an air at 70°C and RH=70% for 60 h showed change in color. The Cu–5at.%Ta alloy showed bright blue, and alloys with 10–30 at.% Ta were all turned to reddish color by oxidation. Among the alloys examined, Cu–24at.%Ta alloy showed the highest oxidation rate under the above condition. The in-depth profiles of Cu–24at.%Ta alloy specimens oxidized for 6–60 h in the air of 70°C and RH=70% indicated existence of metallic Cu-layer on the top of Ta-rich oxide layer and Cu-enriched alloy layer under the oxide film. The metallic copper layer must be caused by diffusion of metallic copper from the Cu-enriched alloy layer to the top of the surface similarly to the oxidation of Cu–Zr alloys at room temperature in a laboratory air. Even Cu–Ta alloys which show very high corrosion resistance in HCl solutions does not always have high corrosion resistance to oxidation in air because of difference in surface film formation process and the resulting compositions and film structure.

Background: Epithelial-mesenchymal transition (EMT) is considered a possible mechanism of distant metastasis or resistance of cancer cells to anticancer drugs. Several reports suggest that eribulin methylate (eribulin) promotes mesenchymal-epithelial transition (MET) both in vitro and in vivo and have shown its inhibition of distant metastasis of engrafted carcinoma. However, no reports have examined the effects of eribulin in a clinical setting. The EXPECT-study investigates EMT/MET markers in metastatic breast cancer (MBC) patients using pleural effusion as a method of liquid biopsy. Objectives: In MBC patients with malignant pleural effusion, we attempted to establish EMT/MET markers using the cancer cells in the pleural effusion, to assess the efficacy and safety of eribulin monotherapy, and to verify the EMT/MET markers as biomarkers in eribulin monotherapy. Study design and eligibility criteria: The EXPECT study is a multicenter, open-label, single-arm phase 2 translational study. Eribulin will be administered at 1.4 mg/m2 on Days (D) 1 and 8 for a 3-week cycle (C), and to obtain the cancer cells from the pleural effusion before and after eribulin administration, paired chest drainage will be performed on C1D1 and C1D8. MBC patients, regardless of their subtype, with pleural effusion are eligible for enrollment, and eribulin monotherapy in the study will be administered based on clinical practice. Therefore, there are no special inclusion/exclusion criteria except for the requirement that all patients be naïve to eribulin. Methods: Spun-down cancer cells in the plural effusion will be processed via the cell block method and embedded in paraffin. An immunohistochemical analysis will be performed using candidate antibodies for EMT/MET markers, such as E-cadherin, cytokeratin (CK) 19, and 34betaE12 (CK1, CK5, CK10, CK14) as epithelial markers and N-cadherin, vimentin, Snail, Slug, Twist-1, ZEB1, ZEB2, ALDH1, and HIF-1alpha as mesenchymal markers, which are all concurrently being assessed in another confirmatory study. The changes in EMT/MET marker expression between pre- and post-treatment will be measured, and the relationship between these changes and the clinical outcome, such as the clinical benefit rate (CBR), progression-free survival, and overall survival, will be assessed. Present and target accrual: The study was just approved by the institutional review board in March 2016 and is open for enrollment. The target accrual is 48 patients total, or 4 patients per month. The sample size calculation was not based on statistical consideration, such as power or type I error. As an illustration for the analysis, the relationship between the changes in the EMT/MET markers and the clinical outcome may be investigated by comparing the CBRs in the two groups with substantial and small changes in the marker expression. If we demonstrate CBRs of 38% and 13% in each group, respectively, then statistical significance will be demonstrated with a 0.10 significance level (2-sided). Citation Format: Watanabe J, Ohtani S, Ikeda M, Takahashi M, Moriya T. A phase II, open-label, multicenter, translational study for biomarkers of eribulin mesylate: Evaluation of the utility of monitoring epithelial-to-mesenchymal transition (EMT) markers on tumor cells in the malignant plural effusion of patients with metastatic breast cancer (EXPECT-study) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-01.

The magnetization M p of proximity-effect-induced superconducting Cu (PEISC) in multifilamentary NbTi/Cu composite conductors has been measured in transverse fields B e smaller than B c1 of the NbTi filament at 4.2 K. The conductors were designed specifically to subtract out the magnetization of the NbTi filaments from magnetization of the conductors. The filament spacing is 1.38 μm and the width of the regular hexagonal filament is 7.60 μm. Twist pitches are 6.9, 13, 20, 94 and 189 mm. M p was investigated as a function of the twist pitch l p and the field amplitude B m . The first penetration field B c1p of the magnetic flux, the decoupling field B dp of the filament coupling, and the width of the M p at a given field are directly proportional to the twist pitch. M p magnetization loops intersect each other for B c1p ⩽ B m ⩽ B dp and decrease suddenly at B dp . The critical current density J cp of PEISC is proportional to B e −2 and its value is 10 kA/m 2 at 7 mT.

In this paper, a macro-level scheduling method is developed to provide high-level planning support for factories with multiple coordinating cells. To model the problem with manageable complexity, detailed operations of a product within a cell are aggregated as a single operation whose processing time is related to the amount of resources allocated. "Overload variables" are introduced and penalized in the objective function. The goal is to properly allocate resources, efficiently handle complicated process plans, and coordinate cells to ensure on-time delivery, low working-in-process inventory, and small resource overload. The formulation obtained is "separable" and can be effectively decomposed by using Lagrangian relaxation. A combined backward and forward dynamic programming (BFDP) method is developed to solve a product sub-problem after a novel transformation of its process plan. The BFDP is further simplified and solved approximately.

The fatigue crack growth behavior of γ-based titanium aluminides (TiAl) with a fine duplex structure and lamellar structure has been investigated by scanning electron microscope (SEM) in situ observation in vacuum at 750°C and room temperature. For the duplex structured material the fatigue crack growth rates are dominated by the maximum stress intensity, particularly at 750°C. The threshold stress intensity range for fatigue crack growth at 750°C is lower than that at room temperature for any corresponding stress ratio. The fatigue crack growth rate at 750°C is affected by creep deformation in front of the crack tip. The severe crack blunting occurs when the stress ratio is 0.5. For the lamellar structured material the scatter of fatigue crack growth data is very large. Small cracks propagate at the stress intensity range below the threshold for long fatigue crack growth. The effects of microstructure on fatigue crack growth are discussed.

The only practical method to visualize electrical trees formed in organic insulating materials has been to section a specimen with a microtome or a diamond cutter, especially in translucent or opaque materials. In our experiment, a 25 MHz ultrasonic transducer was used to scan a specimen within which an electrical tree had been formed. Ultrasonic echo signals reflected from the treeing region were detected by the same transducer and fed to a electronic measuring system. By determining the horizontal coordinates at which each echo signal from the tree was detected, two-dimensional ultrasonic images were obtained for various types of electrical trees in polyethylene. Furthermore, three-dimensional ultrasonic images of bush-type trees were obtained by means of a new detection or measurement method developed by the authors. These images agree well with those obtained microscopically by sectioning the specimen with a microtome.