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A natural pigment, anthocyanin, extracted from purple sweet potato was complexed with smectite group layered clay minerals, a synthetic saponite and a natural montmorillonite. The resulting biohybrid with the synthetic saponite exhibited a clear color change between blue and pink upon exposure to acidic (HCl) and basic (ammonia) vapors. The color change is similar to that of anthocyanin molecule in solution which is due to the change in the molecular structure of anthocyanin. The response for the color change was within 10 min upon exposure to the vapors and was reversible. The present biohybrid composed of environmentally benign chemically stable and non toxic components is regarded as a possible candidate of environmental sensors and smart pigments.

In LUX-Lung 3, afatinib significantly improved progression-free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation-positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX-Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut-off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P

Purpose New molecular targeted agents are needed for patients with non–small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after ≥ 12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R + T790M, and deletion in exon 19 + T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatment-related AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.

This Phase I study determined the maximum-tolerated dose (MTD) of afatinib (Afatinib is an investigational compound and its safety and efficacy have not yet been established) (BIBW 2992; trade name not yet approved by FDA), an irreversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER)1 and 2, up to a dose of 50 mg/day in advanced non-small cell lung cancer (NSCLC), to establish the recommended dose for Phase II. Patients with advanced NSCLC who had received prior platinum-doublet chemotherapy and/or erlotinib/gefitinib therapy, or who were ineligible for, or not amenable to, treatment with established therapies, received oral afatinib once daily. The MTD was determined based on dose-limiting toxicities (DLTs); other assessments included safety, pharmacokinetic profile, antitumour activity according to response evaluation criteria in solid tumours and EGFR/HER1 mutation analysis where possible. Twelve evaluable patients were treated at doses of 20–50 mg/day. One DLT was observed at 50 mg/day in Course 1 (Grade 3 mucositis). The most frequent drug-related adverse events were diarrhoea, dry skin, stomatitis, rash, paronychia and anorexia; most were Grade 1 or 2. Six out of 12 patients had tumour size reductions; durable stable disease was achieved in three patients including one with EGFR/HER1 exon 19 and T790 M mutations. Peak plasma concentrations of afatinib were reached 3–4 h after administration and declined with a half-life of 30–40 h. Afatinib 50 mg/day was well tolerated with an acceptable safety profile during Phase I. Recommended dose for Phase II was defined as 50 mg/day for Japanese patients; the same as for non-Japanese patients.

Adsorption behavior of water, o-xylene and p-xylene vapor to a series of N,N′-hexamethylalkyldiammonium ions [(CH3)3N+(CnH2n+1)(CH3)3N+; where n = 2,3,6,10] exchanged montmorillonites (Kunipia F from Kunimine Ind. Co., Japan; cation exchange capacity of 119 meq (100 g clay)−1 and BENGEL BLIGHT 11 from Hojun, Japan; cation exchange capacity of 78 meq (100 g clay)−1) was investigated. All the organo-clays examined in the present study adsorbed these gases to show their microporous nature. The adsorbed amounts of water, o-xylene and p-xylene increased as the size of N,N′-hexamethylalkyldiammonium was smaller and as the cation exchange capacity of host was larger, showing possible pore volume engineering.

In this paper, we propose the examination of spur mark evidence on inkjet-printed documents. Spur marks are tool marks created by the spur gears in the paper conveyance system of many inkjet printers. The relationship between printouts and printers were investigated by comparing the spur marks found on printed documents with reference spur marks sampled from known printers. The comparison was based on two characteristics of spur marks: pitch and mutual distance. These characteristics extracted the geometric features of spur marks and provided information on the type of spur gears and their location in the paper conveyance system. The spur marks on a printout matched the reference spur marks within three percent of the measured values. Spur marks were considered to be effective class characteristics to identify certain brands of inkjet printers since spur gears are used in many types of these machines.

The utilization of smectite clay, swelling layered silicate, as scaffolds for designing functional nanostructures was overviewed. Surface modification of smectites with organoammonium ions has given hydrophobic and microporous nature to uptake nonionic organic contaminants from environments. The states of the adsorbed nonionic organic compounds have been altered and varied by the modification of smectites as shown by the controlled release and specific catalytic reactions. Cationic species have been easily concentrated on smectites from aqueous phase and the states (orientation and distribution) have been controlled by the co-adsorption of both cationic and nonionic species. The functions of smectite-organic intercalation compounds derived from the precisely controlled nanostructures were introduced in this review.

A document examiner examines handwriting mainly by a qualitative method based on his/her knowledge and experiences. The qualitative examination, compared with the quantitative examination, possesses less objectivity and is believed to be less reliable. However, an examiner's opinion is, in fact, highly reliable. The knowledge and strategies that a document examiner uses is discussed in this paper. Four kinds of classification experiments where diagram-like 36 handwriting samples written by 6 writers were used as stimuli were done by visual inspection and cluster analysis. Results of the experiments suggested that the examiner utilized his knowledge on writing motion even when the classification target was a diagram drawn by the reconstruction of a handwriting sample.

Quercetin (QUER) and luteolin (LUTE) are dietary flavonoids capable of regulating the production of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). However, their mechanisms of action are not fully understood. In lipopolysaccharide-triggered (LPS)-triggered signaling via Toll-like receptor 4 (TLR4), QUER and LUTE suppresses not only the degradation of the inhibitor of kappaB (IkappaB), with resultant activation of nuclear factor-kappaB (NF-kappaB), but also the phosphorylation of p38 and Akt in bone marrow-derived macrophages that have been stimulated with LPS. We report here that, in TNF-alpha-induced signaling, QUER and LUTE significantly suppressed the production of IL-6 and activation of NF-kappaB. Accumulation of lipid rafts, the initial step in the signaling pathway, was significantly inhibited when macrophages were treated with QUER or with LUTE prior to exposure to LPS. Similarly, the accumulation of lipid rafts was inhibited by the flavonoids when B cells were activated via the membrane IgM and when T cells were activated via CD3. In contrast, QUER and LUTE did not inhibit the activation of phorbol myristate acetate-induced NF-kappaB in macrophages. Our observations suggest that QUER and LUTE interact with receptors on the cell surface and suppress the accumulation of lipid rafts that occurs downstream of the activation of the receptors.

Proton knockout reactions on carbon isotopes, p(9–16C,2p)8‐15B, at 250MeV/A were performed for systematic information on weakly to strongly bound 1p valence protons and deeply bound 1s protons. Various information such as energy gap between 1s and 1p orbits, widths of momentum distributions for 1s and 1p orbits, relative (p,2p) yields are obtained.

International audience; Workflow management systems are now widely deployed for handling administrative and production applications. In order that the workflow management systems keep supporting a larger range of applications, several research works have been launched to improve the workflow technology. This paper reports on the CORVETTE [1] project, an experiment in developing a cooperative workflow management system by integrating a workflow management system commercialised by Hitachi Ltd. with a cooperation technology proposed by INRIA. A cooperative workflow management system is a system gathering workflow management functionalities and having capabilities to manage cooperative behaviours characteristics of creative application processes (e.g. in codesign and coengineering). In this kind of applications, interactions between activities are characterised by being more subtle than in traditional applications (i.e. non-scheduled, unpredictable, dynamic, etc.). More precisely, CORVETTE was targeted to support coordination workflow processes of a virtual team working over the internet.

The relationship between the correct ratio of the writer identification and the construction of the character was investigated. Thirty subjects were asked to write 32 kinds of Chinese characters 6 times. Coordinates of each stroke of the characters were measured. After the standardization of the origin and the size, the writers were classified and identified using multidimensional Euclidean distance. In Experiment 1, the number of strokes had little effect on the correct ratio of the identification. In Experiment 2, the relationship between the arrangement of the components of a character and the correct identification ratio was observed. These results were explained by the investigation into the stroke order, pen direction, and interaction between components along with geometrical construction. The results suggest that the investigation based on the motor aspects of writing motion is necessary to the handwriting examination. >

7524 Background: An unmet medical need exists in NSCLC pts after failure of E or G [reversible EGFR tyrosine kinase inhibitors (TKIs)], particularly in pts with T790M EGFR mutations, the most common mechanism of acquired resistance. Afatinib (A), an irreversible erbB family blocker, has preclinical activity against T790M. A was tested in this phase II study in pts enriched for acquired resistance to E or G. Methods: Pts in Japan with Stage IIIB/IV NSCLC (ECOG PS 0–1) who had progressed according to RECIST after 1–2 lines of chemotherapy and ≥12 wks of E or G received 50 mg A orally qd. The primary endpoint was objective tumor response. Results: Of 62 pts (F:48; M:14), 11.3%, 79% and 9.7% had received prior erlotinib, gefitinib or both, respectively. 65% of pts had achieved a prior response with E/G. Median duration between end of prior treatment with E/G and the start of A was 3 wks. 73% of pts were EGFR mutation-positive in their primary tumors. 82% of pts met the definition of acquired resistance to E/G...