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Diurnal variations of the oxidative stress condition of cyanobacteria were measured by field observations and laboratory experiments. In the field experiment, on clear summer days, transparent bottles, filled with surface water, were set up near the water surface, and several depths to 1 m deep. One bottle from each depth was collected every three hours together with the measurement of the photosynthetically active radiation (PAR). In the laboratory experiment, two cyanobacterial species were exposed to gradually increasing then decreasing light intensities. The samples were analyzed with the hydrogen peroxide (H2O2) concentration, the catalase activities (CAT), protein and chlorophyll a (Chl-a) contents. Regardless of difference in cyanobacterial species, similar diurnal trends were obtained. Protein contents did not change for one day experiments. Biologically generated H2O2 increased following the PAR intensity variation, with the delay of a few hours. The H2O2 concentration per protein was given as an increasing function of the exposure period (T) to the PAR. The amount of Chl-a content declined with the H2O2 per protein value. The model was developed to estimate the H2O2 per protein value, elucidating that the effect of the cyanobacterial biomass and the surface layer mixing on the oxidative stress and mortality.

Software clustering is important in program comprehension, and it is applied to architecture recovery and software visualization to analyze the actual software system structure. The detection of omnipresent modules, programs used by many parts of the system such as utility classes, is a well-known issue in software clustering. Omnipresent modules obscure the system structure. The detection and removal of omnipresent modules have been studied for years. However, traditional approaches based on the number of the caller classes remove too many classes, including important domain model classes. In this study, we introduce a method to detect omnipresent modules by calculating a metric called usage equality; it represents the equality in the usage of a class by its caller classes based on the dedication score, which is a weight calculated for inter-class dependency defined in the literature. The developed method was evaluated and compared with traditional methods using real examples. The results show that our method identified omnipresent modules more moderately than the traditional methods to avoid the essential domain classes.

Runt-related transcription factor 1 (RUNX1) is generally considered to function as a tumor suppressor in the development of leukemia, but a growing body of evidence suggests that it has pro-oncogenic properties in acute myeloid leukemia (AML). Here we have demonstrated that the antileukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Increased expression of other RUNX family members, including RUNX2 and RUNX3, compensated for the antitumor effect elicited by RUNX1 silencing, and simultaneous attenuation of all RUNX family members as a cluster led to a much stronger antitumor effect relative to suppression of individual RUNX members. Switching off the RUNX cluster using alkylating agent–conjugated pyrrole-imidazole (PI) polyamides, which were designed to specifically bind to consensus RUNX-binding sequences, was highly effective against AML cells and against several poor-prognosis solid tumors in a xenograft mouse model of AML without notable adverse events. Taken together, these results identify a crucial role for the RUNX cluster in the maintenance and progression of cancer cells and suggest that modulation of the RUNX cluster using the PI polyamide gene-switch technology is a potential strategy to control malignancies.

Technology that facilitates rapid modification of existing business applications is necessary and it has been reported that making the system more adaptable to change is the strongest driver for legacy system modernization. There has been considerable interest in service-oriented architectures or microservices which enables the system to be quickly changed. Refactoring and, in particular, re-modularization operations can be performed to repair the design of a software system. Various approaches have been proposed to support developers during the re-modularization of a software system. The common problem in these efforts is to identify from monolithic applications the candidates of microservices, i.e., the programs or data that can be turned into cohesive, standalone services; this is a tedious manual effort that requires analyzing many dimensions of software architecture views and often heavily relies on the experience and expertise of the expert performing the extraction. To solve this problem, we developed a method that identifies the candidates of microservices from the source code by using software clustering algorithm SArF with the relation of "program groups" and "data" which we defined. Our method also visualizes the extracted candidates to show the relationship between extracted candidates and the whole structure. The candidates and visualization help the developers to capture the overview of the whole system and facilitated a dialogue with customers. We report two case studies to evaluate our results in which we applied our method to an open source application and an industrial application with our results reviewed by developers.

Software clustering techniques have been studied and applied to analyze and visualize the actual structure of legacy applications, which have used program information, e.g., dependencies, as input. However, business data also play an important role in a business system. Revealing which programs actually use data in the current system can give us a key insight when analyzing a long-lived complicated system. In this paper, we calculate indexes indicating how a data entity is used, making use of software clustering, which can be used to detect problematic or characteristic parts of the system. The developed technique can reveal the characteristics of a data entity; i.e., it is used like master data. We applied this technique to two business systems used for many years and found that our technique can help us understand the systems in terms of business data usage. Through case studies, we evaluated the validity of the indexes and showed that software visualization with the indexes can be used to investigate a system in an exploratory way.

ent-Kaurene is a tetracyclic diterpene hydrocarbon and a biosynthetic intermediate of the plant hormone gibberellins. In flowering plants, ent-kaurene is biosynthesized from geranylgeranyl diphosphate (GGDP) by two distinct cyclases, ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS). Recently, the moss Physcomitrella patens ent-kaurene biosynthetic gene was cloned and functionally characterized. The bifunctional ent-kaurene synthase [P. patens CPS/KS (PpCPS/KS)] produces both ent-kaurene and 16α-hydroxy-ent-kaurane from GGDP via ent-copalyl diphosphate. Here, we cloned and analyzed the function of a cDNA encoding bifunctional ent-kaurene synthase from the liverwort Jungermannia subulata [J. subulata CPS/KS (JsCPS/KS)]. JsCPS/KS catalyzes the cyclization reaction of GGDP to produce ent-kaurene but not 16α-hydroxy-ent-kaurane, even though the PpCPS/KS (881 amino acids) and JsCPS/KS (886 amino acids) sequences share 60% identity. To determine the regions and amino acids involved in 16α-hydroxy-ent-kaurane formation, we analyzed the enzymic functions of JsCPS/KS and PpCPS/KS chimeric proteins. When the C-terminal region of PpCPS/KS was exchanged with the JsCPS/KS C-terminal region, the chimeric cyclases produced only ent-kaurene. The replacement of PpCPS/KS Ala710 with Met or Phe produced a JsCPS/KS-type cyclase that converted GGDP to ent-kaurene as the sole product. In contrast, replacing Ala710 with Gly, Cys or Ser did not affect the PpCPS/KS product profile as much as replacement of Cys of JsCPS/KS by Ala. Thus, the hydrophobicity and size of the side chain residue at the PpCPS/KS amino acid 710 is responsible for quenching the ent-kauranyl cation by the addition of a water molecule.

Software clustering techniques have been used to analyze the reality of software structure. The visualization of the detected clusters has also been studied. However, the features implemented by the detected clusters are not obvious and understanding them is a crucial part of the industrial use of software clustering. In this study, we examined the existing information retrieval method and found three major issues it has. We developed technical solutions for each of them: using hierarchical labeling, weighing the words likely representing the feature by considering an architectural convention, and modifying the idf score by the scale of the cluster. The effectiveness of our approach is validated through case studies using actual software products including a COBOL business application. Also, we faced two additional practical problems: effectiveness of the method words and plural and conjugated forms of the words. We found the method name words were less useful than the class name words, and lemmatization was successfully used to normalize the form of the words even in the case of program identifiers.

In this paper, a circular polarization switchable microstrip antenna with a double balanced multiplier that consists of four diodes in a star form is proposed. A 90 deg. phase difference condition of two orthogonal excitation modes on a patch is produced by a didoes' nonlinear coupling of the multiplier. A circular polarization switching (LHCP and RHCP) capability by a bias polarity for diodes is experimentally confirmed.

The influence of plating additives on lattice defects in electrolytic copper made with various amount of plating additives has been investigated by positron annihilation technique. The results show that the copper plated with no leveler and normal amount of brightener includes vacancy clusters corresponding to positron lifetime of about 330 ps. On the other hand, the other samples have no remarkable vacancy clusters. These suggest that plating additives influence not only on the copper surface morphology but also on the formation of the microscopic lattice defects.

Epidermal growth factor receptor (EGFR) is a promising target for anticancer therapy for non-small lung cancer (NSCLC). Mitogen-inducible gene 6 (Mig6) is known to be a negative feedback regulator of EGFR. Mig6 inhibits EGFR kinase activity and promote wild-type EGFR trafficking to the degradation pathway. Down-regulation of Mig6 is found in poor prognostic NSCLC. Previous gene array analysis results suggested that Mig6 is downregulated by runt-related transcription factor 1 (RUNX1), yet the detailed relationship between RUNX1 and Mig6 in NSCLC has not been elucidated. Herein we demonstrate that RUNX1 inhibition is effective for wild-type EGFR NSCLC. Tet-inducible shRNA mediated RUNX1 knockdown in wild-type EGFR cell line LU99A led to the increased expression of Mig6 and decreased expression of phosphorylated form of EGFR as well as deactivation of EGFR/ERK pathway. RUNX1 knockdown subsequently induced apoptosis in LU99A cells. Silencing of Mig6 in LU99A cells promoted the proliferation of these cancer cells and increased expression of phosphorylated form of EGFR, highlighting the importance of this EGFR signaling cascade in the maintenance of wild-type EGFR NSCLC. Indeed, RUNX1 overexpression promoted cell proliferation and decreased expression of Mig6 and increased phosphorylated form of EGFR. Notably Mig6 knockdown in RUNX1 knockdown LU99A cells increased their proliferation rates, indicating that Mig6 plays an important role in RUNX1-mediated pro-oncogenic pathway. We next examined the efficacy of a novel small molecule which specifically binds and inhibits the RUNX1 (We named it as CM). CM was drastically effective for wild-type EGFR NSCLC cell lines A549 and LU99A which are naturally resistant to EGFR Tyrosine kinase inhibitor: gefitinib. In addition, CM suppressed tumor growth of xeno-transplanted A549 cells in immune-deficient mice in vivo. Our study underscores the importance of RUNX1 inhibition therapy in the management of gefitinib-resistant NSCLC patients. Citation Format: Akihiko Matsuo. RUNX1 controls EGFR signaling pathway in non-small cell lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3516. doi:10.1158/1538-7445.AM2017-3516

The participation of tumor necrosis factor-alpha (TNF-alpha) in a IgE-mediated cutaneous reaction in WBB6F1-W/Wv (W/Wv), mast cell deficient, mice and the effect of prednisolone on this cutaneous reaction were investigated. Mice were passively sensitized by an intravenous injection of monoclonal anti-dinitrophenol (DNP) IgE, and their ears challenged epicutaneously with dinitrofluorobenzene 24 h later. The cutaneous reaction estimated by ear thickness reached a peak 48-72 h after the antigen challenge. A monoclonal anti-tumor necrosis factor (TNF)-alpha antibody inhibited the IgE-mediated cutaneous reaction. An increase of TNF-alpha mRNA was demonstrated 4 h after the application of antigen by the reverse transcriptase-polymerase chain reaction. The injection of recombinant murine TNF-alpha induced a cutaneous reaction which peaked at 24 h in nonsensitized mice. Prednisolone at doses of 3 to 10 mg/kg clearly inhibited the IgE-mediated cutaneous reaction, however, it did not affect the expression of TNF-alpha-mRNA. Prednisolone at doses of 1 to 10 mg/kg clearly inhibited the TNF-alpha-induced cutaneous reaction. These results suggest that TNF-alpha plays a role in the IgE-mediated cutaneous reaction in W/Wv mice and that prednisolone inhibits the cutaneous reaction at least in part by inhibiting the action of TNF-alpha.

Due to the inhibition of 5-lipoxygenase-activating protein (FLAP), BAY x1005 is a new selective inhibitor of leukotriene synthesis. The effects of BAY x1005 on the antigen- and bacterial lipopolysaccharide (LPS)-induced airway hyperresponsiveness in guinea pigs were investigated. Six times provocation of aeroantigen caused biphasic increases in airway resistance which peaked at 1 hr (immediate phase reaction) and 4 hrs (late phase reaction). It also caused airway hyperreactivity to acetylcholine. BAY x1005 at doses of 10mg/kg and 30mg/kg significantly inhibited antigen-induced increase in respiratory resistance (Rrs) at 1 and 4 hrs after the last antigen challenge. Simultaneously, BAY x1005 inhibited the antigen-induced airway hyperresponsiveness at doses of 10 and 30mglkg and airway eosinophilia (bronchoalveolar lavage study) at a dose of 30 mg/kg. In addition, BAY x1005 at a dose of 30mg/kg inhibited bacterial LPS-induced airway hyperreactivity to acetylcholine. In this model, BAY x1005 did not affect the increase of the number of leukocytes in bronchoalveolar lavage fluid. These results suggest that BAY x1005 is a potent anti-asthmatic agent with an inhibitory action to airway hyperreactivity.

To facilitate understanding the architecture of a software system, we developed SArF Map technique that visualizes software architecture from feature and layer viewpoints using a city metaphor. SArF Map visualizes implicit software features using our previous study, SArF dependency-based software clustering algorithm. Since features are high-level abstraction units of software, a generated map can be directly used for high-level decision making such as reuse and also for communications between developers and non-developer stakeholders. In SArF Map, each feature is visualized as a city block, and classes in the feature are laid out as buildings reflecting their software layer. Relevance between features is represented as streets. Dependency links are visualized lucidly. Through open source and industrial case studies, we show that the architecture of the target systems can be easily overviewed and that the quality of their packaging designs can be quickly assessed., Comment: 10 pages, 16 figures, 2 tables. This is the accepted version of a paper presented at the 21st IEEE International Conference on Program Comprehension (ICPC2013), San Francisco, CA, USA, May 2013, pp.43-52

The effects of a novel leukotriene (LT) C 4 D 4 antagonist, BAY-x-7195 on experimental allergic reactions in airway and skin were compared to that of ONO-1078. BAY-x-7195 showed an antagonistic action to LTD4-induced bronchoconstriction in vitro and in vivo. In in vitro experiments, BAY-x-7195 inhibited LTD4-induced contraction of isolated guinea pig tracheal muscle (pA2=8.03). BAY-x-7195 at doses of 3 – 30 mg/kg clearly inhibited LTD4-induced increases in respiratory resistance (Rrs) in guinea pigs. In contrast, BAY-x-7195 inhibited significantly U-46619-induced increases in Rrs at a dose of 30 mg/kg in guinea pigs. BAY-x-7195 at doses of 3 — 30 mg/kg inhibited the aerosolized antigen-induced biphasic increase in Rrs in guinea pigs. Moreover BAY-x-7195 inhibited repeated aeroantigen-induced airway hyperreactivity in guinea pigs. In mice, aeroantigen-induced airway inflammation were clearly inhibited by BAY-x-7195. These results show the efficacy of BAY-x-7195 against the antigen-induced increase in airway resistance and antigen-induced airway hyperreactivity in guinea pigs and mice, probably due to anti-LTD4 antagonistic action and the inhibition of antigen-induced airway inflammation.

The effect of a novel thromboxane A2 receptor antagonist, BAY-u-3405, on experimental allergic airway and skin reactions was studied in vivo. At doses of 3-30 mg/kg BAY-u-3405 clearly inhibited the U-46619-induced increase in respiratory resistance (Rrs) in guinea pigs. BAY-u-3405 at doses of 3 and 30 mg/kg inhibited the aerosolized antigen-induced biphasic increase in respiratory resistance in guinea pigs. Moreover, BAY-u-3405 inhibited repeated aeroantigen-induced airway hyperactivity and airway inflammation in mice. In IgE antibody-mediated biphasic skin reactions in mice, both immediate and late-phase reactions were inhibited by 10 mg/kg of BAY-u-3405. These results demonstrate the efficacy of BAY-u-3405 on the antigen-induced late-phase reactions in the airway and skin in guinea pigs and mice, and antigen-induced airway hyperactivity in mice.

Along with the rapid evolution of cloud computing, outsourcing service has also changed significantly. One of the main concerns for cloud computing is security. In particular, it becomes more important to handle client data securely in such a consulting service. In this paper, we present the design and implementation of Software as a Service (SaaS) application framework using Information Gateway that enables cloud service while maintaining data confidentiality. By setting up Information Gateway in the client environment, the executing location is dynamically controlled according to whether the data contains confidential information or not, and only secured data is routed to the SaaS application in the cloud. Therefore, if the data policy is registered by the client administrator beforehand, the user is able to use the cloud service appropriately without being aware of it. Moreover, we also describe that existing applications can be easily ported into the SaaS application because our framework allows application developers to define complicated routing logic briefly.

In this study, we propose a novel technique to generate the test data for COBOL programs using an SMT solver. The proposed technique can consider the comparison between a character string and a numerical value. The technique can also consider the significant figures for each variable. With the experiment, we confirmed that our technique can correctly generate test data for COBOL programs of a real enterprise system.

Software clustering is one of the important techniques to comprehend software systems. However, presented techniques to date require human interactions to refine clustering results. In this paper, we proposed a novel dependency-based software clustering algorithm, SArF. SArF has two characteristics. First, SArF eliminates the need of the omnipresent-module-removing step which requires human interactions. Second, the objective of SArF is to gather relevant software features or functionalities into a cluster. To achieve them, we defined the Dedication score to infer the importance of dependencies and utilized Modularity Maximization to cluster weighted directed graphs. Two case studies and extensive comparative evaluations using open source and industrial systems show that SArF could successfully decompose the systems fitting to the authoritative decompositions from a feature viewpoint without any tailored setups and that SArF was superior to existing dependency-based software clustering studies. Besides, the case studies show that there exist measurable authoritativeness limits and that SArF nearly reached the limits., Comment: 10 pages, 9 figures, 7 tables. This is the accepted version of a paper presented at the 28th IEEE International Conference on Software Maintenance (ICSM2012), Riva del Garda, Trento, Italy, Sep 2012, pp.462-471

Semantic web service is proposed to support the automation of service discovery, composition and invocation. However, it is still difficult for common users to compose semantic web services or generate them from web services. In order to alleviate such pains, in this paper we present Flow Editor: a visual semantic web service composition tool based on OWL-S specification. It has several advantages, including visual service composition by drag-and-drop, semi-automatic semantic web service generation, visual control construct supports and so on. In practice, the tool is already applied to help users solve realistic problems by creating and exporting new on-demand services.

Atherosclerosis is characterised by unusual growth of vascular smooth muscle cells (VSMCs) in the intima. We examined the effects of histamine on human VSMCs and the VSMC-derived cell line, ISS10. Histamine enhanced phosphoinositide hydrolysis, increased cytoplasmic Ca z+ level and stimulated the transcription of c-fos protooncogene, which resulted in DNA synthesis and the enhancement of proMMP-1 expression. These results indicate that histamine may play some roles in the pathological process of atherosclerosis and raise the possibility that mast cells migrating into the atherosclerotic foci are involved in the process of atherosclerogenesis.

In software maintenance, both product metrics and process metrics are required to predict faults effectively. However, process metrics cannot be always collected in practical situations. To enable accurate fault prediction without process metrics, we define a new metric, ImpactScale. ImpactScale is the quantified value of change impact, and the change propagation model for ImpactScale is characterized by probabilistic propagation and relation-sensitive propagation. To evaluate ImpactScale, we predicted faults in two large enterprise systems using the effort-aware models and Poisson regression. The results showed that adding ImpactScale to existing product metrics increased the number of detected faults at 10% effort (LOC) by over 50%. ImpactScale also improved the predicting model using existing product metrics and dependency network measures.

Web services technology is mainly designed for the interoperability among machines, whose inputs and outputs are defined in the form of XML schema without presentation information, hence it is unable to present the execution results of Web services to human beings directly and friendly. To address this problem, an ontology-based method and a rendering engine are proposed in this paper. In the method, domain ontology is utilized to annotate the types of inputs and outputs of a Web service. Templates are generated and stored according to each type described in the ontology. When rendering, the rendering engine first finds out the type of the execution results, and then retrieves corresponding templates with the URL of the type, finally recursively renders the execution results with the templates. In addition, a management interface is proposed for managing the templates.

Three new gymnomitrane sesquiterpenoids have been isolated from the liverwort Marsupella emarginata var. patens together with the known (−)-gymnomitrene and (−)-ar-curcumene. Their structures and absolute configurations have been determined on the basis of chemical and spectroscopic evidence as well as from the results of an X-ray analysis of a derivative. We also describe the ring expansion reaction of the gymnomitrane framework and the chemosystematics of the genus Marsupella.

Momilactones A (1) and B (2), which have been identified as phytoalexins in rice, were isolated from extracts of the moss Hypnum plumaeforme. This is the first isolation and identification of momilactones as allelochemicals from a bryophyte. H. plumaeforme produces considerable amounts of momilactones (isolated yield: 8.4 mg/Kg plant for 1; 4.2 mg/Kg for 2). EtOAc extracts from H. plumaeforme and 2 showed growth inhibitory activity against angiosperms, moss, and liverwort plants. On the other hand, the growth of H. plumaeforme was insensitive to its extract and 2. Our finding suggests that momilactones play an important role as allelochemicals in this moss.

A cell suspension culture of the liverwort Jungermannia subulata was established from callus tissue induced by culturing spores. From the suspension culture, three new ent-kaurane-type diterpenoids were isolated together with three previously reported ent-kaurane-type diterpenoids. Five ent-kaurane-type diterpenoids were isolated from the intact J. subulata, two of which were new compounds. Their structures were determined by spectroscopic methods, chemical reaction, and X-ray crystallographic analysis.

This paper introduces a variable classification technique to support the maintenance of COBOL application systems. It classifies program variables according to what domain entities they represent. It supports various types of software maintenance. In a system modification, it is necessary to identify the source code related to the problem at hand properly. This maintenance phase, called the impact analysis, involves significant costs in large-scale business application systems. The variable classification presented supports finding all variables to be checked and modified. In a system restructuring, the variable classification is needed to restructure data declarations. The behavior of the classification can be changed interactively with several parameters. This paper also presents these parameters and how to set them for each type of maintenance task.

We propose a new method to support the maintenance of large scale business application systems, and discuss its implementation. Large scale business applications handle huge numbers of data items. To improve the maintenance of business application systems, our method proposes integrating the following features: (1) a high level control flow diagram which displays an unstructured program in a structured form; (2) a data dependency diagram which is essential in understanding business rules; and (3) ripple effect analysis functions to find the side effects of program modification. This paper also describes an execution path model and a repository which enable us to efficiently implement the above features. The system has been developed to reflect the discussions with software maintainers.

Production of IgE caused by repeated topical application of 2,4-dinitrofluorobenzene (DNFB) to the ears of BALB/c mice was investigated. Ear thickness increased in proportion to the number of applications. Eczematous changes of the skin included marked infiltration of neutrophils, eosinophils, and monocytes and hypertrophy of the epidermis. Ear thickness due to inflammation reached a maximum 24 hours after the second, third, fourth, and fifth applications. The strong expression of interferon-γ and IL-2 messenger RNA (mRNA) in the skin lesions indicated the participation of Th1 type helper T cells in the delayed-type hypersensitivity reaction. After the fifth application, the mice showed an immediate cutaneous reaction in addition to the delayed-type hypersensitivity reaction. The immediate reaction appeared within 1 hour of application. Hapten-specific IgE also was detected in serum from the mice, and the expression of germline and productive Ce mRNA was detected in cervical lymph nodes, whereas productive Ce mRNA was detected in the spleen. These results indicate that five topical applications of DNFB to the ear produce local eczematous dermatitis and increase serum hapten-specific IgE level in mice. Eczematous dermatitis is mainly caused by Th1 type T cells, and IgE production is mediated by Th2 type T cells in the cervical lymph nodes. In addition, IgE class switching occurs in the cervical nodes and IgE production occurs in both lymph nodes and spleen. (J Allergy Clin Immunol 1997;100:S39-44.)