Information-Technology Promotion Agency

Ketamine is metabolized by cytochrome P450 (CYP) leading to production of pharmacologically active products and contributing to drug excretion. We identified the CYP enzymes involved in the N-demethylation of ketamine enantiomers using pooled human liver microsomes and microsomes from human B-lymphoblastoid cells that expressed CYP enzymes. The kinetic data in human liver microsomes for the (R)- and (S)-ketamine N-demethylase activities could be analyzed as two-enzyme systems. The K(m) values were 31 and 496 microM for (R)-ketamine, and 24 and 444 microM for (S)-ketamine. Among the 12 cDNA-expressed CYP enzymes examined, CYP2B6, CYP2C9, and CYP3A4 showed high activities for the N-demethylation of both enantiomers at the substrate concentration of 1 mM. CYP2B6 had the lowest K(m) value for the N-demethylation of (R)- and (S)-ketamine (74 and 44 microM, respectively). Also, the intrinsic clearance (CL(int): V(max)/K(m)) of CYP2B6 for the N-demethylation of both enantiomers were 7 to 13 times higher than those of CYP2C9 and CYP3A4. Orphenadrine (CYP2B6 inhibitor, 500 microM) and sulfaphenazole (CYP2C9 inhibitor, 100 microM) inhibited the N-demethylase activities for both enantiomers (5 microM) in human liver microsomes by 60 to 70%, whereas cyclosporin A (CYP3A4 inhibitor, 100 microM) failed to inhibit these activities. In addition, the anti-CYP2B6 antibody inhibited these activities in human liver microsomes by 80%, whereas anti-CYP2C antibody and anti-CYP3A4 antibody failed to inhibit these activities. These results suggest that the high affinity/low capacity enzyme in human liver microsomes is mediated by CYP2B6, and the low affinity/high capacity enzyme is mediated by CYP2C9 and CYP3A4. CYP2B6 mainly mediates the N-demethylation of (R)- and (S)-ketamine in human liver microsomes at therapeutic concentrations (5 microM).

Recent methylome analyses of the entire Arabidopsis thaliana genome using various mutants have provided detailed information about the DNA methylation pattern and its function. However, information about DNA methylation in other plants is limited, partly because of the lack of mutants. To study DNA methylation in rice (Oryza sativa) we applied homologous recombination-mediated gene targeting to generate targeted disruptants of OsDRM2, a rice orthologue of DOMAINS REARRANGED METHYLASE 1 and 2 (DRM1/2), which encode DNA methyltransferases responsible for de novo and non-CG methylation in Arabidopsis. Whereas Arabidopsis drm1 drm2 double mutants showed no morphological alterations, targeted disruptants of rice OsDRM2 displayed pleiotropic developmental phenotypes in both vegetative and reproductive stages, including growth defects, semi-dwarfed stature, reductions in tiller number, delayed heading or no heading, abnormal panicle and spikelet morphology, and complete sterility. In these osdrm2 disruptants, a 13.9% decrease in 5-methylcytosine was observed by HPLC analysis. The CG and non-CG methylation levels were reduced in RIRE7/CRR1 retrotransposons, and in 5S rDNA repeats. Associated transcriptional activation was detected in RIRE7/CRR1. Furthermore, de novo methylation by an RNA-directed DNA methylation (RdDM) process involving transgene-derived exogenous small interfering RNA (siRNA) was deficient in osdrm2-disrupted cells. Impaired growth and abnormal DNA methylation of osdrm2 disruptants were restored by the complementation of wild-type OsDRM2 cDNA. Our results suggest that OsDRM2 is responsible for de novo, CG and non-CG methylation in rice genomic sequences, and that DNA methylation regulated by OsDRM2 is essential for proper rice development in both vegetative and reproductive stages.

Euglena gracilis (E. gracilis) has been proposed as one of the most attractive microalgae species for biodiesel and biomass production, which exhibits a number of shapes, such as spherical, spindle-shaped, and elongated. Shape is an important biomarker for E. gracilis, serving as an indicator of biological clock status, photosynthetic and respiratory capacity, cell-cycle phase, and environmental condition. The ability to prepare E. gracilis of uniform shape at high purities has significant implications for various applications in biological research and industrial processes. Here, we adopt a label-free, high-throughput, and continuous technique utilizing inertial microfluidics to separate E. gracilis by a key shape parameter-cell aspect ratio (AR). The microfluidic device consists of a straight rectangular microchannel, a gradually expanding region, and five outlets with fluidic resistors, allowing for inertial focusing and ordering, enhancement of the differences in cell lateral positions, and accurate separation, respectively. By making use of the shape-activated differences in lateral inertial focusing dynamic equilibrium positions, E. gracilis with different ARs ranging from 1 to 7 are directed to different outlets.

Abstract Acetylene semihydrogenation is a key technology for producing polymer‐grade ethylene from crude ethylene. Ni‐based catalysts are promising alternatives to noble‐metals for this process. However, achieving high catalytic activity and selectivity remains a big challenge. We report a novel catalyst design based on high‐entropy intermetallics (HEI), which provide thermally stable isolated Ni without excess counterpart metals and achieve exceptionally high performance. Intermetallic NiGa was multi‐metalized to a (NiFeCu)(GaGe), where the Ni and Ga sites were partially substituted with Fe/Cu and Ge, respectively, without altering the parent CsCl‐type structure. The NiFeCuGaGe/SiO 2 HEI catalyst completely inhibited ethylene overhydrogenation even at complete acetylene conversion, and exhibited five‐times higher activity than other 3d‐transition‐metal‐based catalysts. The DFT study showed that the surface energy decreased by multi‐metallization, which drastically weakened ethylene adsorption.

As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Since 2015, three IL-17 inhibitors of secukinumab and ixekizumab, anti-IL-17A antibodies, and brodalumab, an anti-IL-17 receptor antibody, and two anti-IL-23p19 antibodies of guselkumab and risankizumab, have also been launched. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors and patient background factors, sharing such information with patients. The following can be listed as points to be considered for the selection of biologics: drug effects (e.g. strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g. infections, administration-related reactions and relationships with other comorbidities), convenience for patients (e.g. hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration) and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors.

Purpose A significant amount of empirical research has been conducted on the socio‐economic (sociological, psychological, economic) aspects of information security, such as the phenomenon of individuals who are willing to take security measures, but often do not. There is a growing body of research relating to individual behaviour and decision making and the purpose of this paper is to analyze a survey on the behaviour of individuals who implement information security measures. Design/methodology/approach To promote effective information security measures, this paper refers to research on the psychology of persuasion from the field of social psychology. A survey was conducted into determinants for changing attitudes through persuasive messages, and the results were analysed. A questionnaire was used and the authors built a demonstrative experimental environment, which analysed in detail attitudinal changes in an individuals' behaviour. Findings The authors found differences in behaviour regarding the intent to implement measures discovered from the responses to the questionnaire as well as from actual conduct in the demonstrative experiment. Originality/value It is original to adopt a model defined by social psychology, especially Protection Motivation Theory and Elaborative Likelihood Model. The authors conducted both questionnaire survey and the psychological experiment.

Using multiplatform satellite data and 13 typhoon passages from 1998 through 2004, an empirical relationship to assess typhoon‐forced primary production (PP) enhancement in the outer shelf of the East China Sea is introduced. The constructed relationship requires variables of typhoon maximum sustained wind, typhoon transit speed and bottom depth of the location below the typhoon track. As this relationship does not require ocean color data, it enabled us to reconstruct the interannual and interdecadal variations of typhoon‐forced PP enhancement from 2004 back to 1980. Typhoon‐forced PP enhancements and typhoon contributions to summer‐fall new production during El Niño years tended to be higher than those during La Niña years. Typhoon‐enhanced PP also has shown a tendency to be higher during the 1991–2004 period than during the 1980–1990 one. The method we detail in this study is applicable for other tropical cyclone trajectory basins.

Cost estimation is a very crucial field for software developing companies. The acceptance of an estimation technique is highly dependent on estimation accuracy. Often, this accuracy is only determined after an initial application. Possible further steps for improving the underlying estimation model typically do not influence the decision on whether to discard the technique or deploy it. In addition, most estimation techniques do not explicitly support the evolution of the underlying estimation model in an iterative manner. This increases the risk of overlooking some important cost drivers or data inconsistencies. This paper presents an enhanced process for developing a CoBRA® cost estimation model by systematically including iterative analysis and feedback cycles, and its evaluation in a software development unit of Oki Electric Industry Co., Ltd., Japan. During the model improvement cycles, estimation accuracy was improved from an initial 120% down to 14%. In addition, lessons learned with the iterative development approach are described.

In this paper, we propose a highly accurate, automatic malware-classification method, which extracts features by conducting static analysis of malware samples and the structure of malware source code. In the proposed extraction method, the presence and absence of particular pairs of consecutive Application Program Interface function calls (APIs) in the API-sequence graph are compared with those in the executable code for a sample within which malware features have been identified. To determine the degree of similarity between samples, Dice's coefficient is applied. To visualize the grouping of samples with similar features, we use hierarchical cluster analysis based on the extracted features. The results of the analysis are presented as a dendrogram with colored nodes for each family name. To evaluate the proposed method, we set up a malware-analysis system comprising a combination of disassembler, control-flow analyzer, API-sequence extractor, similarity calculator and hierarchical cluster analyzer. We acquired 4,684 malware samples, from 1,821 of which we successfully extracted API sequences to which we applied our proposed classification method. We found that the automatic hierarchical cluster analysis was processed rapidly, with significant clusters of variant groups obtained.

Lymph node (LN) stromal cells (LNSCs) form the functional structure of LNs and play an important role in lymphocyte survival and the maintenance of immune tolerance. Despite their broad spectrum of function, little is known about LNSC responses during microbial infection. In this study, we demonstrate that LNSC subsets display distinct kinetics following vaccinia virus infection. In particular, compared with the expansion of other LNSC subsets and the total LN cell population, the expansion of fibroblastic reticular cells (FRCs) was delayed and sustained by noncirculating progenitor cells. Notably, newly generated FRCs were preferentially located in perivascular areas. Viral clearance in reactive LNs preceded the onset of FRC expansion, raising the possibility that viral infection in LNs may have a negative impact on the differentiation of FRCs. We also found that MHC class II expression was upregulated in all LNSC subsets until day 10 postinfection. Genetic ablation of radioresistant stromal cell-mediated Ag presentation resulted in slower contraction of Ag-specific CD4(+) T cells. We propose that activated LNSCs acquire enhanced Ag-presentation capacity, serving as an extrinsic brake system for CD4(+) T cell responses. Disrupted function and homeostasis of LNSCs may contribute to immune deregulation in the context of chronic viral infection, autoimmunity, and graft-versus-host disease.

Propane dehydrogenation has been a promising method for producing propylene that has the potentials to meet the increasing global demand for propylene. However, owing to the restricted equilibrium conversion caused by the high endothermicity, even the Pt-based catalysts, which exhibit high activity and selectivity, severely suffer significantly from coke formation and/or nanoparticle sintering at realistic reaction temperatures, resulting in a short catalyst lifetime. As a result, few innovative catalysts in terms of catalytic activity, selectivity, and stability, have been produced. In this Review, we focus on the characteristics of single-atom-like Pt sites for PDH and attempt to provide suggestions for developing highly efficient catalysts. First, we briefly describe the fundamental strategies. Following that, the remarkable catalysis is addressed by three different distinct sorts of state-of-the-art single-atom-like Pt catalysts are discussed. Additionally, we present other promising catalyst design approaches that are not based on single-atom-like Pt catalysts, as well as future research challenges in this field.

Analogy-based cost estimation provides a useful and intuitive means to support decision making in software project management. It derives a cost estimate required for completing a project from information about similar past projects, namely the analogues. While on average this method provides a relatively accurate cost estimate there remains a possibility of large estimation errors. In this paper, we empirically tested the hypothesis that "using more homogeneous analogues produces a more reliable cost estimate" using a software engineering data repository established by the software engineering center (SEC), Information-technology Promotion Agency, Japan. This testing showed that low and high homogeneity projects had a large variation in estimation reliability. For instance, the difference was 22.9% (p = 0.021) in terms of percentage to get accurate estimates (better than Median of Magnitude of Relative Error).

BACKGROUND: Loneliness and social isolation are elevated in older adults and associated with a range of detrimental outcomes. Despite this, there has been little research on these phenomena or on similarities and differences in their occurrence or combination in older Japanese adults. The current study aims to (i) determine what factors are associated with social isolation and loneliness among older adults in Japan; and (ii) describe the characteristics of individuals who are socially isolated but not lonely, as well as those who feel lonely but are not socially isolated. METHODS: Data were analysed from 13 766 adults aged ≥65 years who participated in the 2019 wave of the Japan Gerontological Evaluation Study. Poisson regression analysis was used to examine associations. RESULTS: Among older Japanese adults, the attributes of higher age, male gender, lower socioeconomic status, being a welfare recipient, and having depressive symptoms were associated with social isolation, while lower socioeconomic status, unemployment, welfare receipt, and poor physical and mental health were associated with loneliness. In addition, better educated, and mentally and physically healthy people were less likely to feel lonely even when socially isolated, while people who were not working and who had mental or physical health problems were more likely to feel lonely even if they were not socially isolated. DISCUSSION: Our results indicate that in order to reduce unwanted social isolation and loneliness among older Japanese adults, in the first instance the focus should be on those individuals who are socioeconomically disadvantaged and unhealthy.

Amputees usually perceive vivid awareness of their lost body parts after the amputation (phantom limbs). Phantom limb pain (PLP) is intense pain that is felt in the phantom limb. The mechanism of PLP is still unclear, but the major hypothesis is that it is derived from dysfunction of the brain. There are a few neurorehabilitation techniques using a mirror or virtual reality (VR) that present the visual image of a phantom limb to the patients, and this produce the movement perception of their phantom limb. Here, we developed a multimodal (visual, auditory, and tactile) VR system to obtain the perception of voluntary phantom limb movements. We applied this system to five PLP patients for three tactile feedback conditions as a pilot study. In conclusion, four of the five patients reported pain amelioration, up to 86% decrease in the tactile feedback condition. In addition, our results demonstrated that the best suited condition of feedback-sense modalities depends on the patient. These results suggest that this system can be applied to a rehabilitation platform to offer flexible neurorehabilitation regimens for each patient.

SUMMARY Many methods have been proposed to detect intrusions; for example, the pattern matching method on known intrusion patterns and the statistical approach to detecting deviation from normal activities. We investigated a new method for detecting intrusions based on the number of system calls during a user’s network activity on a host machine. This method attempts to separate intrusions from normal activities by using discriminant analysis, a kind of multivariate analysis. We can detect intrusions by analyzing only 11 system calls occurring on a host machine by discriminant analysis with the Mahalanobis’ distance, and can also tell whether an unknown sample is an intrusion. Our approach is a lightweight intrusion detection method, given that it requires only 11 system calls for analysis. Moreover, our approach does not require user profiles or a user activity database in order to detect intrusions. This paper explains our new method for the separation of intrusions and normal behavior by discriminant analysis, and describes the classification method by which

Using daily sea ice data derived from satellite‐borne sensors and atmospheric data, we examined processes controlling the variation of sea ice extent in the Northern Hemisphere. The daily ice motion field was computed from imagery of the Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave Imager (SSM/I) for seven winters (December to April) from 1991/1992 to 1997/1998, by employing the maximum cross‐correlation method. In order to examine mechanisms of the temporal variation of the ice extent, we analyzed 50 specified lines across the daily ice edge. Although a high correlation between the ice motion and the geostrophic wind speed was observed in all the ice edge areas, the degree for correlation between the speed of the ice edge displacement and the wind speed varied with region. The degree for response of the ice edge speed to the wind speed largely depended upon that of the ice edge speed to the ice motion. The following mechanisms controlling the variation of ice extent for regions in the Northern Hemisphere were anticipated. In the Barents Sea, Bering Sea, and the Sea of Okhotsk the ice extent advances by wind‐driven ice advection and the daily scale variation of the ice extent were also controlled by the variation in wind speed. In contrast, the ice extent in the Labrador Sea and the Greenland Sea seemed to be considerably affected by oceanographic factors such as the location of the thermal front and was not related to the variation in wind speed. The regional difference of the variation mechanism was also reflected in the interannual variation in maximum ice extent.

We investigated rapid protection effect by estradiol on corticosterone (CORT)-induced suppression of synaptic transmission. Rapid suppression by 1 μM CORT of long-term potentiation (LTP) at CA3-CA1 synapses was abolished via coperfusion of 1 nM estradiol. N-methyl-D-aspartate (NMDA) receptor-derived field excitatory postsynaptic potential (NMDA-R-fEPSP) was used to analyze the mechanisms of these events. Estradiol abolished CORT-induced suppression of NMDA-R-fEPSP slope. This CORT-induced suppression was abolished by calcineurin inhibitor, and the rescue effect by estradiol on the CORT-induced suppression was inhibited by mitogen-activated protein (MAP) kinase inhibitor. The CORT-induced suppressions of LTP and NMDA-R-fEPSP slope were abolished by glucocorticoid receptor (GR) antagonist, and the restorative effects by estradiol on these processes were mimicked by estrogen receptor α (ERα) and ERβ agonists. Taken together, estradiol rapidly rescued LTP and NMDA-R-fEPSP slope from CORT-induced suppressions. A GR→calcineurin pathway is involved in these suppressive effects. The rescue effects by estradiol are driven via ERα or ERβ→MAP kinase pathway. Synaptic/extranuclear GR, ERα, and ERβ probably participate in these rapid events. Mass-spectrometric analysis determined that acute hippocampal slices used for electrophysiological measurements contained 0.48 nM estradiol less than exogenously applied 1 nM. In vivo physiological level of 8 nM estradiol could protect the intact hippocampus against acute stress-induced neural suppression.

The software projects are considered to be successful if the cost and the duration are within the estimated ones and the quality is satisfactory. To attain project success, the project management, in which the final status of project is estimated, must be incorporated.In this paper, we consider estimation of the final status(that is, successful or unsuccessful) of project by applying Bayesian classifier to metrics data collected from project. In order to attain high estimation accuracy rate, we must select only a set of appropriate metrics to be applied. Here we consider two selection methods: the first method by the experts and the second method by the statistical test.Then we conducted an experiment using 28 project data and 29 metrics data in an organization of a certain company. The result showed that the method by the test gave higher accuracy rates than the method by the experts, and Bayesian classifier with the test method is effective to estimate project success.

Companies increasingly recognize that software and IT play a significant role for their current and future business strategies. Therefore, it is important to align IT/software-related strategies with the business goals across the organization. Currently, little experience exists regarding how to effectively create this missing business-IT link. For this purpose, the GQM+Strategies <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">®</sup> approach was developed to support companies in aligning IT/software-related strategies with business goals through measurement. This paper focuses on facilitating the approach for aligning IT/software projects with an organization's higher-level goals. Lessons learned from applying the approach in the context of the Japanese Information-technology Promotion Agency (IPA), specifically its Software Engineering Center (SEC), are presented. The transparent documentation of goals and strategies, and the collection of key performance indicators were helpful for effectively aligning the projects with overall organizational goals and strategies as well as for evaluating the degree of alignment and the risk of misalignment.

BACKGROUND: Maintaining oral health is one of the global public health challenges. Income and out-of-pocket payments for dental care services are predictors of dental care utilisation. Although public assistance programmes guarantee income security for impoverished people, access barriers other than financial costs may cause unmet dental care needs. We aimed to explore the potential sociodemographic factors determining dental care utilisation among recipients of public assistance in Japan using linkage data of public assistance database and medical assistance claim data administered by municipalities. METHODS: This was a retrospective cohort study involving a sample of public assistance recipients. We extracted the recipients' sociodemographic data (age, sex, household number, employment status, nationality, disability certificates, and long-term care status) in January 2016 and observed them until December 2016 to identify incidences of dental care utilisation as outcomes. We performed a multivariable modified Poisson regression analysis with a robust standard error estimator to calculate the incidence ratio (IR) of dental care utilisation in each variable. RESULTS: We identified a total of 4497 recipients at risk. Among them, 839 recipients used dental care services. Younger age was associated with a higher incidence of dental care utilisation. The female recipients had a higher incidence of dental care utilisation when compared to the male ones (adjusted IR, 1.22; 95% confidence interval [CI], 1.08-1.38). Immigrant recipients had a higher incidence of dental care utilisation than the Japanese ones (IR, 1.53; 95% CI, 1.16-2.01). Recipients with mental disabilities had higher incidences than those without disability certificates (IR, 1.30; 95% CI, 1.08-1.56). CONCLUSIONS: Non-financial sociodemographic inequities in dental care utilisation stemming from age, sex, nationality, and presence of mental disability were found despite minimum income protection and equitable financial dental service access amongst public assistance recipients in Japan. Providing targeted preventive care and treatments for dental care among underserved populations is required to tackle oral health inequities.