Search results for: Hiroaki Watanabe
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 45

Search results for: Hiroaki Watanabe

15 Waste Management in a Hot Laboratory of Japan Atomic Energy Agency – 3: Volume Reduction and Stabilization of Solid Waste

Authors: Masaumi Nakahara, Sou Watanabe, Hiromichi Ogi, Atsuhiro Shibata, Kazunori Nomura

Abstract:

In the Japan Atomic Energy Agency, three types of experimental research, advanced reactor fuel reprocessing, radioactive waste disposal, and nuclear fuel cycle technology, have been carried out at the Chemical Processing Facility. The facility has generated high level radioactive liquid and solid wastes in hot cells. The high level radioactive solid waste is divided into three main categories, a flammable waste, a non-flammable waste, and a solid reagent waste. A plastic product is categorized into the flammable waste and molten with a heating mantle. The non-flammable waste is cut with a band saw machine for reducing the volume. Among the solid reagent waste, a used adsorbent after the experiments is heated, and an extractant is decomposed for its stabilization. All high level radioactive solid wastes in the hot cells are packed in a high level radioactive solid waste can. The high level radioactive solid waste can is transported to the 2nd High Active Solid Waste Storage in the Tokai Reprocessing Plant in the Japan Atomic Energy Agency.

Keywords: high level radioactive solid waste, advanced reactor fuel reprocessing, radioactive waste disposal, nuclear fuel cycle technology

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14 Analysis of Brain Activities due to Differences in Running Shoe Properties

Authors: Kei Okubo, Yosuke Kurihara, Takashi Kaburagi, Kajiro Watanabe

Abstract:

Many of the ever-growing elderly population require exercise, such as running, for health management. One important element of a runner’s training is the choice of shoes for exercise; shoes are important because they provide the interface between the feet and road. When we purchase shoes, we may instinctively choose a pair after trying on many different pairs of shoes. Selecting the shoes instinctively may work, but it does not guarantee a suitable fit for running activities. Therefore, if we could select suitable shoes for each runner from the viewpoint of brain activities, it would be helpful for validating shoe selection. In this paper, we describe how brain activities show different characteristics during particular task, corresponding to different properties of shoes. Using five subjects, we performed a verification experiment, applying weight, softness, and flexibility as shoe properties. In order to affect the shoe property’s differences to the brain, subjects run for ten min. Before and after running, subjects conducted a paced auditory serial addition task (PASAT) as the particular task; and the subjects’ brain activities during the PASAT are evaluated based on oxyhemoglobin and deoxyhemoglobin relative concentration changes, measured by near-infrared spectroscopy (NIRS). When the brain works actively, oxihemoglobin and deoxyhemoglobin concentration drastically changes; therefore, we calculate the maximum values of concentration changes. In order to normalize relative concentration changes after running, the maximum value are divided by before running maximum value as evaluation parameters. The classification of the groups of shoes is expressed on a self-organizing map (SOM). As a result, deoxyhemoglobin can make clusters for two of the three types of shoes.

Keywords: brain activities, NIRS, PASAT, running shoes

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13 Total and Leachable Concentration of Trace Elements in Soil towards Human Health Risk, Related with Coal Mine in Jorong, South Kalimantan, Indonesia

Authors: Arie Pujiwati, Kengo Nakamura, Noriaki Watanabe, Takeshi Komai

Abstract:

Coal mining is well known to cause considerable environmental impacts, including trace element contamination of soil. This study aimed to assess the trace element (As, Cd, Co, Cu, Ni, Pb, Sb, and Zn) contamination of soil in the vicinity of coal mining activities, using the case study of Asam-asam River basin, South Kalimantan, Indonesia, and to assess the human health risk, incorporating total and bioavailable (water-leachable and acid-leachable) concentrations. The results show the enrichment of As and Co in soil, surpassing the background soil value. Contamination was evaluated based on the index of geo-accumulation, Igeo and the pollution index, PI. Igeo values showed that the soil was generally uncontaminated (Igeo ≤ 0), except for elevated As and Co. Mean PI for Ni and Cu indicated slight contamination. Regarding the assessment of health risks, the Hazard Index, HI showed adverse risks (HI > 1) for Ni, Co, and As. Further, Ni and As were found to pose unacceptable carcinogenic risk (risk > 1.10-5). Farming, settlement, and plantation were found to present greater risk than coal mines. These results show that coal mining activity in the study area contaminates the soils by particular elements and may pose potential human health risk in its surrounding area. This study is important for setting appropriate countermeasure actions and improving basic coal mining management in Indonesia.

Keywords: coal mine, risk, trace elements, soil

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12 Pilot Trial of Evidence-Based Integrative Group Therapy to Improve Executive Functioning among Adults: Implications for Community Mental Health and Training Clinics

Authors: B. Parchem, M. Watanabe, D. Modrakovic, L. Mathew, A. Franklin, M. Cao, R. E. Broudy

Abstract:

Objective: Executive functioning (EF) deficits underlie several mental health diagnoses including ADHD, anxiety, and depression. Community mental health clinics face extensive waitlists for services with many referrals involving EF deficits. A pilot trial of a four-week group therapy was developed using key components from Cognitive-Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), and mindfulness with an aim to improve EF skills and offer low-fee services. Method: Eight adults (M = 34.5) waiting for services at a community clinic were enrolled in a four-week group therapy at an in-house training clinic for doctoral trainees. Baseline EF, pre-/post-intervention ADHD and distress symptoms, group satisfaction, and curriculum helpfulness were assessed. Results: Downward trends in ADHD and distress symptoms pre/post-intervention were not significant. Favorable responses on group satisfaction and helpfulness suggest clinical utility. Conclusion: Preliminary pilot data from a brief group therapy to improve EF may be an efficacious, acceptable, and feasible intervention for adults waiting for services at community mental health and training clinics where there are high demands and limits to services and staffs.

Keywords: executive functioning, cognitive-behavioral therapy, dialectical behavior therapy, mindfulness, adult group therapy

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11 Development of Nondestructive Imaging Analysis Method Using Muonic X-Ray with a Double-Sided Silicon Strip Detector

Authors: I-Huan Chiu, Kazuhiko Ninomiya, Shin’ichiro Takeda, Meito Kajino, Miho Katsuragawa, Shunsaku Nagasawa, Atsushi Shinohara, Tadayuki Takahashi, Ryota Tomaru, Shin Watanabe, Goro Yabu

Abstract:

In recent years, a nondestructive elemental analysis method based on muonic X-ray measurements has been developed and applied for various samples. Muonic X-rays are emitted after the formation of a muonic atom, which occurs when a negatively charged muon is captured in a muon atomic orbit around the nucleus. Because muonic X-rays have higher energy than electronic X-rays due to the muon mass, they can be measured without being absorbed by a material. Thus, estimating the two-dimensional (2D) elemental distribution of a sample became possible using an X-ray imaging detector. In this work, we report a non-destructive imaging experiment using muonic X-rays at Japan Proton Accelerator Research Complex. The irradiated target consisted of polypropylene material, and a double-sided silicon strip detector, which was developed as an imaging detector for astronomical observation, was employed. A peak corresponding to muonic X-rays from the carbon atoms in the target was clearly observed in the energy spectrum at an energy of 14 keV, and 2D visualizations were successfully reconstructed to reveal the projection image from the target. This result demonstrates the potential of the non-destructive elemental imaging method that is based on muonic X-ray measurement. To obtain a higher position resolution for imaging a smaller target, a new detector system will be developed to improve the statistical analysis in further research.

Keywords: DSSD, muon, muonic X-ray, imaging, non-destructive analysis

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10 Bi-Liquid Free Surface Flow Simulation of Liquid Atomization for Bi-Propellant Thrusters

Authors: Junya Kouwa, Shinsuke Matsuno, Chihiro Inoue, Takehiro Himeno, Toshinori Watanabe

Abstract:

Bi-propellant thrusters use impinging jet atomization to atomize liquid fuel and oxidizer. Atomized propellants are mixed and combusted due to auto-ignitions. Therefore, it is important for a prediction of thruster’s performance to simulate the primary atomization phenomenon; especially, the local mixture ratio can be used as indicator of thrust performance, so it is useful to evaluate it from numerical simulations. In this research, we propose a numerical method for considering bi-liquid and the mixture and install it to CIP-LSM which is a two-phase flow simulation solver with level-set and MARS method as an interfacial tracking method and can predict local mixture ratio distribution downstream from an impingement point. A new parameter, beta, which is defined as the volume fraction of one liquid in the mixed liquid within a cell is introduced and the solver calculates the advection of beta, inflow and outflow flux of beta to a cell. By validating this solver, we conducted a simple experiment and the same simulation by using the solver. From the result, the solver can predict the penetrating length of a liquid jet correctly and it is confirmed that the solver can simulate the mixing of liquids. Then we apply this solver to the numerical simulation of impinging jet atomization. From the result, the inclination angle of fan after the impingement in the bi-liquid condition reasonably agrees with the theoretical value. Also, it is seen that the mixture of liquids can be simulated in this result. Furthermore, simulation results clarify that the injecting condition affects the atomization process and local mixture ratio distribution downstream drastically.

Keywords: bi-propellant thrusters, CIP-LSM, free-surface flow simulation, impinging jet atomization

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9 Effect of Nanostructure on Hydrogen Embrittlement Resistance of the Severely Deformed 316LN Austenitic Steel

Authors: Frank Jaksoni Mweta, Nozomu Adachi, Yoshikazu Todaka, Hirokazu Sato, Yuta Sato, Hiromi Miura, Masakazu Kobayashi, Chihiro Watanabe, Yoshiteru Aoyagi

Abstract:

Advances in the consumption of hydrogen fuel increase demands of high strength steel pipes and storage tanks. However, high strength steels are highly sensitive to hydrogen embrittlement. Because the introduction of hydrogen into steel during the fabrication process or from the environment is unavoidable, it is essential to improve hydrogen embrittlement resistance of high strength steels through microstructural control. In the present study, the heterogeneous nanostructure with a tensile strength of about 1.8 GPa and the homogeneous nanostructure with a tensile strength of about 2.0 GPa of 316LN steels were generated after 92% heavy cold rolling and high-pressure torsion straining, respectively. The heterogeneous nanostructure is composed of twin domains, shear bands, and lamellar grains. The homogeneous nanostructure is composed of uniformly distributed ultrafine nanograins. The influence of heterogeneous and homogenous nanostructures on the hydrogen embrittlement resistance was investigated. The specimen for each nanostructure was electrochemically charged with hydrogen for 3, 6, 12, and 24 hours, respectively. Under the same hydrogen charging time, both nanostructures show almost the same concentration of the diffusible hydrogen based on the thermal desorption analysis. The tensile properties of the homogenous nanostructure were severely affected by the diffusible hydrogen. However, the diffusible hydrogen shows less impact on the tensile properties of the heterogeneous nanostructure. The difference in embrittlement behavior between the heterogeneous and homogeneous nanostructures was elucidated based on the mechanism of the cracks' growth observed in the tensile fractography. The hydrogen embrittlement was suppressed in the heterogeneous nanostructure because the twin domain became an obstacle for crack growth. The homogeneous nanostructure was not consisting an obstacle such as a twin domain; thus, the crack growth resistance was low in this nanostructure.

Keywords: diffusible hydrogen, heterogeneous nanostructure, homogeneous nanostructure, hydrogen embrittlement

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8 The Role of Cognitive Control and Social Camouflage Associated with Social Anxiety Autism Spectrum Conditions

Authors: Siqing Guan, Fumiyo Oshima, Eiji Shimizu, Nozomi Tomita, Toru Takahashi, Hiroaki Kumano

Abstract:

Risk factors for social anxiety in autism spectrum conditions involve executive attention, emotion regulation, and thought regulation as processes of cognitive dysregulation. Social camouflaging behaviors as strategies used to mask and/or compensate for autism characteristics during social interactions in autism spectrum conditions have also been emphasized. However, the role of cognitive dysregulation and social camouflaging related to social anxiety in autism spectrum conditions has not been clarified. Whether these factors are specific to social anxiety in autism spectrum conditions or common to social anxiety independent of autism spectrum conditions needs to be clarified. Here, we explored risk factors specific to social anxiety in autism spectrum conditions and general risk factors for social anxiety independent of autism spectrum conditions. From the Japanese participants in early adulthood (age=18~39) of the online survey in Japan, those who exceeded the Japanese version Autism-Spectrum Quotient cutoff (33 points or more )were divided into the autism spectrum conditions group (ASC; N=255, mean age=32.08, SD age=5.16)and those who did not exceed the cutoff were divided into the non-autism spectrum conditions group (Non-ASC; N=255, mean age=31.70, SD age=5.09). Using the Japanese versions of the Social Phobia Scale, the Social Interaction Anxiety Scale, and the Short Fear of Negative Evaluation Scale, a composite score for social anxiety was calculated using a method of principal. We also measured emotional control difficulties using the Difficulties in Emotion Regulation Scale, executive attention using the Effortful Control Scale for Adults, rumination using the Rumination-Reflection Questionnaire, and worry using the Penn State Worry Questionnaire. This study was passed through the review of the Ethics Committee. No conflicts of interest. Multiple regression analysis with forced entry method was used to predict social anxiety in the ASC and non-ASC groups separately, based on executive attention, emotion dysregulation, worry, rumination, and social camouflage. In the ASC group, emotion dysregulation (β=.277, p<.001), worry (β=.162, p<.05), assimilation (β=.308, p<.001) and masking (β=.275, p<.001) were significant predictors of social anxiety (F (7,247) = 45.791, p <.001, R2=.565). In the non-ASC groups,emotion dysregulation (β=.171, p<.05), worry (β=.344,p <.001), assimilation (β=.366,p <.001) and executive attention (β=-.132,p <.05) were significant predictors of social anxiety (F (7,207) =47.333, p <.001, R2=.615).The findings suggest that masking was shown to be a risk factor for social anxiety specific to autism spectrum conditions, while emotion dysregulation, worry, and assimilation were shown to be common risk factors for social anxiety, regardless of autism spectrum conditions. In addition, executive attention is a risk factor for social anxiety without autism spectrum conditions.

Keywords: autism spectrum, cognitive control, social anxiety, social camouflaging

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7 Designing Mobile Application to Motivate Young People to Visit Cultural Heritage Sites

Authors: Yuko Hiramatsu, Fumihiro Sato, Atsushi Ito, Hiroyuki Hatano, Mie Sato, Yu Watanabe, Akira Sasaki

Abstract:

This paper presents a mobile phone application developed for sightseeing in Nikko, one of the cultural world heritages in Japan, using the BLE (Bluetooth Low Energy) beacon. Based on our pre-research, we decided to design our application for young people who walk around the area actively, but know little about the tradition and culture of Nikko. One solution is to construct many information boards to explain; however, it is difficult to construct new guide plates in cultural world heritage sites. The smartphone is a good solution to send such information to such visitors. This application was designed using a combination of the smartphone and beacons, set in the area, so that when a tourist passes near a beacon, the application displays information about the area including a map, historical or cultural information about the temples and shrines, and local shops nearby as well as a bus timetable. It is useful for foreigners, too. In addition, we developed quizzes relating to the culture and tradition of Nikko to provide information based on the Zeigarnik effect, a psychological effect. According to the results of our trials, tourists positively evaluated the basic information and young people who used the quiz function were able to learn the historical and cultural points. This application helped young visitors at Nikko to understand the cultural elements of the site. In addition, this application has a function to send notifications. This function is designed to provide information about the local community such as shops, local transportation companies and information office. The application hopes to also encourage people living in the area, and such cooperation from the local people will make this application vivid and inspire young visitors to feel that the cultural heritage site is still alive today. This is a gateway for young people to learn about a traditional place and understand the gravity of preserving such areas.

Keywords: BLE beacon, smartphone application, Zeigarnik effect, world heritage site, school trip

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6 Clinical Applications of Amide Proton Transfer Magnetic Resonance Imaging: Detection of Brain Tumor Proliferative Activity

Authors: Fumihiro Ima, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi

Abstract:

It is important to know growth rate of brain tumors before surgery because it influences treatment planning including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without administration of contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients and WHO grade 4 in 2 patients), meningioma WHO grade1 in 2 patients and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW-signals than that in low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW-signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.

Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation

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5 Clinical Applications of Amide Proton Transfer Magnetic Resonance Imaging: Detection of Brain Tumor Proliferative Activity

Authors: Fumihiro Imai, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi

Abstract:

It is important to know the growth rate of brain tumors before surgery because it influences treatment planning, including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without the administration of a contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after a clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients, and WHO grade 4 in 2 patients), meningioma WHO grade 1 in 2 patients, and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW signals than that low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.

Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation

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4 Assessing the Effect of Urban Growth on Land Surface Temperature: A Case Study of Conakry Guinea

Authors: Arafan Traore, Teiji Watanabe

Abstract:

Conakry, the capital city of the Republic of Guinea, has experienced a rapid urban expansion and population increased in the last two decades, which has resulted in remarkable local weather and climate change, raise energy demand and pollution and treating social, economic and environmental development. In this study, the spatiotemporal variation of the land surface temperature (LST) is retrieved to characterize the effect of urban growth on the thermal environment and quantify its relationship with biophysical indices, a normalized difference vegetation index (NDVI) and a normalized difference built up Index (NDBI). Landsat data TM and OLI/TIRS acquired respectively in 1986, 2000 and 2016 were used for LST retrieval and Land use/cover change analysis. A quantitative analysis based on the integration of a remote sensing and a geography information system (GIS) has revealed an important increased in the LST pattern in the average from 25.21°C in 1986 to 27.06°C in 2000 and 29.34°C in 2016, which was quite eminent with an average gain in surface temperature of 4.13°C over 30 years study period. Additionally, an analysis using a Pearson correlation (r) between (LST) and the biophysical indices, normalized difference vegetation index (NDVI) and a normalized difference built-up Index (NDBI) has revealed a negative relationship between LST and NDVI and a strong positive relationship between LST and NDBI. Which implies that an increase in the NDVI value can reduce the LST intensity; conversely increase in NDBI value may strengthen LST intensity in the study area. Although Landsat data were found efficient in assessing the thermal environment in Conakry, however, the method needs to be refined with in situ measurements of LST in the future studies. The results of this study may assist urban planners, scientists and policies makers concerned about climate variability to make decisions that will enhance sustainable environmental practices in Conakry.

Keywords: Conakry, land surface temperature, urban heat island, geography information system, remote sensing, land use/cover change

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3 Waste Management in a Hot Laboratory of Japan Atomic Energy Agency – 1: Overview and Activities in Chemical Processing Facility

Authors: Kazunori Nomura, Hiromichi Ogi, Masaumi Nakahara, Sou Watanabe, Atsuhiro Shibata

Abstract:

Chemical Processing Facility of Japan Atomic Energy Agency is a basic research field for advanced back-end technology developments with using actual high-level radioactive materials such as irradiated fuels from the fast reactor, high-level liquid waste from reprocessing plant. In the nature of a research facility, various kinds of chemical reagents have been offered for fundamental tests. Most of them were treated properly and stored in the liquid waste vessel equipped in the facility, but some were not treated and remained at the experimental space as a kind of legacy waste. It is required to treat the waste in safety. On the other hand, we formulated the Medium- and Long-Term Management Plan of Japan Atomic Energy Agency Facilities. This comprehensive plan considers Chemical Processing Facility as one of the facilities to be decommissioned. Even if the plan is executed, treatment of the “legacy” waste beforehand must be a necessary step for decommissioning operation. Under this circumstance, we launched a collaborative research project called the STRAD project, which stands for Systematic Treatment of Radioactive liquid waste for Decommissioning, in order to develop the treatment processes for wastes of the nuclear research facility. In this project, decomposition methods of chemicals causing a troublesome phenomenon such as corrosion and explosion have been developed and there is a prospect of their decomposition in the facility by simple method. And solidification of aqueous or organic liquid wastes after the decomposition has been studied by adding cement or coagulants. Furthermore, we treated experimental tools of various materials with making an effort to stabilize and to compact them before the package into the waste container. It is expected to decrease the number of transportation of the solid waste and widen the operation space. Some achievements of these studies will be shown in this paper. The project is expected to contribute beneficial waste management outcome that can be shared world widely.

Keywords: chemical processing facility, medium- and long-term management plan of JAEA facilities, STRAD project, treatment of radioactive waste

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2 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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1 Performance and Limitations of Likelihood Based Information Criteria and Leave-One-Out Cross-Validation Approximation Methods

Authors: M. A. C. S. Sampath Fernando, James M. Curran, Renate Meyer

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Model assessment, in the Bayesian context, involves evaluation of the goodness-of-fit and the comparison of several alternative candidate models for predictive accuracy and improvements. In posterior predictive checks, the data simulated under the fitted model is compared with the actual data. Predictive model accuracy is estimated using information criteria such as the Akaike information criterion (AIC), the Bayesian information criterion (BIC), the Deviance information criterion (DIC), and the Watanabe-Akaike information criterion (WAIC). The goal of an information criterion is to obtain an unbiased measure of out-of-sample prediction error. Since posterior checks use the data twice; once for model estimation and once for testing, a bias correction which penalises the model complexity is incorporated in these criteria. Cross-validation (CV) is another method used for examining out-of-sample prediction accuracy. Leave-one-out cross-validation (LOO-CV) is the most computationally expensive variant among the other CV methods, as it fits as many models as the number of observations. Importance sampling (IS), truncated importance sampling (TIS) and Pareto-smoothed importance sampling (PSIS) are generally used as approximations to the exact LOO-CV and utilise the existing MCMC results avoiding expensive computational issues. The reciprocals of the predictive densities calculated over posterior draws for each observation are treated as the raw importance weights. These are in turn used to calculate the approximate LOO-CV of the observation as a weighted average of posterior densities. In IS-LOO, the raw weights are directly used. In contrast, the larger weights are replaced by their modified truncated weights in calculating TIS-LOO and PSIS-LOO. Although, information criteria and LOO-CV are unable to reflect the goodness-of-fit in absolute sense, the differences can be used to measure the relative performance of the models of interest. However, the use of these measures is only valid under specific circumstances. This study has developed 11 models using normal, log-normal, gamma, and student’s t distributions to improve the PCR stutter prediction with forensic data. These models are comprised of four with profile-wide variances, four with locus specific variances, and three which are two-component mixture models. The mean stutter ratio in each model is modeled as a locus specific simple linear regression against a feature of the alleles under study known as the longest uninterrupted sequence (LUS). The use of AIC, BIC, DIC, and WAIC in model comparison has some practical limitations. Even though, IS-LOO, TIS-LOO, and PSIS-LOO are considered to be approximations of the exact LOO-CV, the study observed some drastic deviations in the results. However, there are some interesting relationships among the logarithms of pointwise predictive densities (lppd) calculated under WAIC and the LOO approximation methods. The estimated overall lppd is a relative measure that reflects the overall goodness-of-fit of the model. Parallel log-likelihood profiles for the models conditional on equal posterior variances in lppds were observed. This study illustrates the limitations of the information criteria in practical model comparison problems. In addition, the relationships among LOO-CV approximation methods and WAIC with their limitations are discussed. Finally, useful recommendations that may help in practical model comparisons with these methods are provided.

Keywords: cross-validation, importance sampling, information criteria, predictive accuracy

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