Search results for: Hideki Yamamoto

Authors: Reiko Yamamoto

Abstract:

This paper reports on a project to integrate Japanese (as a first language) and English (as a second language) education. This study focuses on the mutual effects of the two languages on the linguistic proficiency of elementary school students. The research team consisted of elementary school teachers and researchers at a university. The participants of the experiment were students between 3^rd and 6^th grades at an elementary school. The research process consisted of seven steps: 1) specifying linguistic proficiency; 2) developing the cross-curriculum of L1 and L2; 3) forming can-do statements; 4) creating a self-evaluation questionnaire; 5) executing the self-evaluation questionnaire at the beginning of the school year; 6) instructing L1 and L2 based on the curriculum; and 7) executing the self-evaluation questionnaire at the beginning of the next school year. In Step 1, the members of the research team brainstormed ways to specify elementary school students’ linguistic proficiency that can be observed in various scenes. It was revealed that the teachers evaluate their students’ linguistic proficiency on the basis of the students’ utterances, but also informed by their non-verbal communication abilities. This led to the idea that competency for understanding others’ minds through the use of physical movement or bodily senses in communication in L1 – to sympathize with others – can be transferred to that same competency in communication in L2. Based on the specification of linguistic proficiency that L1 and L2 have in common, a cross-curriculum of L1 and L2 was developed in Step 2. In Step 3, can-do statements based on the curriculum were also formed, building off of the action-oriented approach from the Common European Framework of Reference for Languages (CEFR) used in Europe. A self-evaluation questionnaire consisting of the main can-do statements was given to the students between 3^rd grade and 6^th grade at the beginning of the school year (Step 4 and Step 5), and all teachers gave L1 and L2 instruction based on the curriculum to the students for one year (Step 6). The same questionnaire was given to the students at the beginning of the next school year (Step 7). The results of statistical analysis proved the enhancement of the students’ linguistic proficiency. This verified the validity of developing the cross-curriculum of L1 and L2 and adapting it in elementary school. It was concluded that elementary school students do not distinguish between L1 and L2, and that they just try to understand others’ minds through physical movement or senses in any language.

Keywords: cross curriculum of L1 and L2, elementary school education, language proficiency, sympathy with others

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Authors: Apichaya Aneksampant, Xuefei Tu, Masami Fukushima, Mitsuo Yamamoto

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The restoration of seaweed beds recovery has been developed using a fertilization technique for supplying dissolved iron to barren coastal areas. The fertilizer is composed of iron oxides as a source of iron and compost as humic substance (HS) source, which can serve as chelator of iron to stabilize the dissolved species under oxic seawater condition. However, elution mechanisms of iron from iron oxide surfaces have not sufficiently elucidated. In particular, roles of microbial activities in the elution of iron from the fertilizer are not sufficiently understood. In the present study, a fertilizer (iron oxide/compost = 1/1, v/v) was incubated in a water tank at Mashike coast, Hokkaido Japan. Microorganisms in the 6-month fertilizer were isolated and identified as Exiguobacterium oxidotolerans sp. (T-2-2). The identified bacteria were inoculated to perform iron elution test in a postgate B medium, prepared in artificial seawater. Hematite was used as a model iron oxide and anthraquinone-2,7-disolfonate (AQDS) as a model for HSs. The elution test performed in presence and absence of bacteria inoculation. ICP-AES was used to analyze total iron and a colorimetric technique using ferrozine employed for the determination of ferrous ion. During the incubation period, sample contained hematite and T-2-2 in both presence and absence of AQDS continuously showed the iron elution and reached at the highest concentration after 9 days of incubation and then slightly decrease to stabilize within 20 days. Comparison to the sample without T-2-2, trace amount of iron was observed, suggesting that iron elution to seawater can be attributed to bacterial activities. The levels of total organic carbon (TOC) in the culture solution with hematite decreased. This may be to the adsorption of organic compound, AQDS, to hematite surfaces. The decrease in UV-vis absorption of AQDS in the culture solution also support the results of TOC that AQDS was adsorbed to hematite surfaces. AQDS can enhance the iron elution, while the adsorption of organic matter suppresses the iron elution from hematite.

Keywords: anthraquinone-2, 7-disolfonate, barren ground, E.oxidotolerans sp., hematite, humic substances, iron elution

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Authors: Reiko Yamamoto

Abstract:

This paper reports on a joint research project in which a researcher in applied linguistics and elementary school teachers in Japan explored new ways to realize emotional synchrony in a classroom in childhood education. The primary purpose of this project was to develop a cross-curriculum of the first language (L1) and second language (L2) based on the concept of plurilingualism. This concept is common in Europe, and can-do statements are used in forming the standard of linguistic proficiency in any language; these are attributed to the action-oriented approach in the Common European Framework of Reference for Languages (CEFR). CEFR has a basic tenet of language education: improving communicative competence. Can-do statements are classified into five categories based on the tenet: reading, writing, listening, speaking/ interaction, and speaking/ speech. The first approach of this research was to specify the linguistic proficiency of the children, who are still developing their L1. Elementary school teachers brainstormed and specified the linguistic proficiency of the children as the competency needed to synchronize with others – teachers or peers – physically and mentally. The teachers formed original can-do statements in language proficiency on the basis of the idea that emotional synchrony leads to understanding others in communication. The research objectives are to determine the effect of language education based on the newly developed curriculum and can-do statements. The participants of the experiment were 72 third-graders in Uji Elementary School, Japan. For the experiment, 17 items were developed from the can-do statements formed by the teachers and divided into the same five categories as those of CEFR. A can-do checklist consisting of the items was created. The experiment consisted of three steps: first, the students evaluated themselves using the can-do checklist at the beginning of the school year. Second, one year of instruction was given to the students in Japanese and English classes (six periods a week). Third, the students evaluated themselves using the same can-do checklist at the end of the school year. The results of statistical analysis showed an enhancement of linguistic proficiency of the students. The average results of the post-check exceeded that of the pre-check in 12 out of the 17 items. Moreover, significant differences were shown in four items, three of which belonged to the same category: speaking/ interaction. It is concluded that children can get to understand others’ minds through physical and emotional synchrony. In particular, emotional synchrony is what teachers should aim at in childhood education.

Keywords: elementary school education, emotional synchrony, language proficiency, sympathy with others

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Authors: H. Ishii, S. Araki, H. Yamamoto

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In recent years, the carbon dioxide (CO2) separation technology is required in terms of the reduction of emission of global warming gases and the efficient use of fossil fuels. Since the emission amount of CO2 gas occupies the large part of greenhouse effect gases, it is considered that CO2 have the most influence on global warming. Therefore, we need to establish the CO2 separation technologies with high efficiency at low cost. In this study, we focused on the membrane separation compared with conventional separation technique such as distillation or cryogenic separation. In this study, we prepared carbonate-ceramic dual-phase membranes to separate CO2 at high temperature. As porous ceramic substrate, the (Pr0.9La0.1)2(Ni0.74Cu0.21Ga0.05)O4+σ, La0.6Sr0.4Ti0.3 Fe0.7O3 and Ca0.8Sr0.2Ti0.7Fe0.3O3-α (PLNCG, LSTF and CSTF) were examined. PLNCG, LSTF and CSTF have the perovskite structure. The perovskite structure has high stability and shows ion-conducting doped by another metal ion. PLNCG, LSTF and CSTF have perovskite structure and has high stability and high oxygen ion diffusivity. PLNCG, LSTF and CSTF powders were prepared by a solid-phase process using the appropriate carbonates or oxides. To prepare porous substrates, these powders mixed with carbon black (20 wt%) and a few drops of polyvinyl alcohol (5 wt%) aqueous solution. The powder mixture were packed into stainless steel mold (13 mm) and uniaxially pressed into disk shape under a pressure of 20 MPa for 1 minute. PLNCG, LSTF and CSTF disks were calcined in air for 6 h at 1473, 1573 and 1473 K, respectively. The carbonate mixture (Li2CO3/Na2CO3/K2CO3: 42.5/32.5/25 in mole percent ratio) was placed inside a crucible and heated to 793 K. Porous substrates were infiltrated with the molten carbonate mixture at 793 K. Crystalline structures of the fresh membranes and after the infiltration with the molten carbonate mixtures were determined by X-ray diffraction (XRD) measurement. We confirmed the crystal structure of PLNCG and CSTF slightly changed after infiltration with the molten carbonate mixture. CO2 permeation experiments with PLNCG-carbonate, LSTF-carbonate and CSTF-carbonate membranes were carried out at 773-1173 K. The gas mixture of CO2 (20 mol%) and He was introduced at the flow rate of 50 ml/min to one side of membrane. The permeated CO2 was swept by N2 (50 ml/min). We confirmed the effect of ceramic materials and temperature on the CO2 permeation at high temperature.

Keywords: membrane, perovskite structure, dual-phase, carbonate

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Authors: Y. Muto, S. Araki, H. Yamamoto

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The separation of oxygen is one key technology to improve the efficiency and to reduce the cost for the processed of the partial oxidation of the methane and the condensation of the carbon dioxide. Particularly, carbon dioxide at high concentration would be obtained by the combustion using pure oxygen separated from air. However, the oxygen separation process occupied the large part of energy consumption. Therefore, it is considered that the membrane technologies enable to separation at lower cost and lower energy consumption than conventional methods. In this study, it is examined that the separation of oxygen using membranes of mixed conductors. Oxygen permeation through the membrane is occurred by the following three processes. At first, the oxygen molecules dissociate into oxygen ion at feed side of the membrane, subsequently, oxygen ions diffuse in the membrane. Finally, oxygen ions recombine to form the oxygen molecule. Therefore, it is expected that the membrane of thickness and material, or catalysts of the dissociation and recombination affect the membrane performance. However, there is little article about catalysts for the dissociation and recombination. We confirmed the performance of La0.6Sr0.4Co1.0O3-δ (LSC) based catalyst which was commonly used as the dissociation and recombination. It is known that the adsorbed amount of oxygen increase with the increase of doped Fe content in B site of LSC. We prepared the catalysts of La0.1Sr0.9Co0.9Fe0.1O3-δ(C9F1), La0.1Sr0.9Co0.5Fe0.5O3-δ(C5F5) and La0.1Sr0.9Co0.3Fe0.7O3-δ(C7F3). Also, we used Pr2NiO4 type mixed conductor as a membrane material. (Pr0.9La0.1)2(Ni0.74Cu0.21Ga0.05)O4+δ(PLNCG) shows the high oxygen permeability and the stability against carbon dioxide. Oxygen permeation experiments were carried out using a homemade apparatus at 850 -975 °C. The membrane was sealed with Pyrex glass at both end of the outside dense alumina tubes. To measure the oxygen permeation rate, air was fed to the film side at 50 ml min-1, helium as the sweep gas and reference gas was fed at 20 ml min-1. The flow rates of the sweep gas and the gas permeated through the membrane were measured using flow meter and the gas concentrations were determined using a gas chromatograph. Then, the permeance of the oxygen was determined using the flow rate and the concentration of the gas on the permeate side of the membrane. The increase of oxygen permeation was observed with increasing temperature. It is considered that this is due to the catalytic activities are increased with increasing temperature. Another reason is the increase of oxygen diffusivity in the bulk of membrane. The oxygen permeation rate is improved by using catalyst of LSC or LSCF. The oxygen permeation rate of membrane with LSCF showed higher than that of membrane with LSC. Furthermore, in LSCF catalysts, oxygen permeation rate increased with the increase of the doped amount of Fe. It is considered that this is caused by the increased of adsorbed amount of oxygen.

Keywords: membrane separation, oxygen permeation, K2NiF4-type structure, mixed conductor

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Authors: E. Nakamachi, K. Matsumoto, K. Yamamoto, Y. Morita, H. Sakamoto

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In recently, electromagnetic and mechanical stimulations have been recognized as the effective extracellular environment stimulation technique to enhance the defected peripheral nerve tissue regeneration. In this study, we developed a new hybrid bioreactor by adopting 50 Hz uniform alternative current (AC) magnetic stimulation and 4% strain mechanical stimulation. The guide tube for nerve regeneration is mesh structured tube made of biodegradable polymer, such as polylatic acid (PLA). However, when neural damage is large, there is a possibility that peripheral nerve undergoes necrosis. So it is quite important to accelerate the nerve tissue regeneration by achieving enhancement of nerve axonal extension rate. Therefore, we try to design and fabricate the system that can simultaneously load the uniform AC magnetic field stimulation and the stretch stimulation to cells for enhancement of nerve axonal extension. Next, we evaluated systems performance and the effectiveness of each stimulation for rat adrenal pheochromocytoma cells (PC12). First, we designed and fabricated the uniform AC magnetic field system and the stretch stimulation system. For the AC magnetic stimulation system, we focused on the use of pole piece structure to carry out in-situ microscopic observation. We designed an optimum pole piece structure using the magnetic field finite element analyses and the response surface methodology. We fabricated the uniform AC magnetic field stimulation system as a bio-reactor by adopting analytically determined design specifications. We measured magnetic flux density that is generated by the uniform AC magnetic field stimulation system. We confirmed that measurement values show good agreement with analytical results, where the uniform magnetic field was observed. Second, we fabricated the cyclic stretch stimulation device under the conditions of particular strains, where the chamber was made of polyoxymethylene (POM). We measured strains in the PC12 cell culture region to confirm the uniform strain. We found slightly different values from the target strain. Finally, we concluded that these differences were allowable in this mechanical stimulation system. We evaluated the effectiveness of each stimulation to enhance the nerve axonal extension using PC12. We confirmed that the average axonal extension length of PC12 under the uniform AC magnetic stimulation was increased by 16 % at 96 h in our bio-reactor. We could not confirm that the axonal extension enhancement under the stretch stimulation condition, where we found the exfoliating of cells. Further, the hybrid stimulation enhanced the axonal extension. Because the magnetic stimulation inhibits the exfoliating of cells. Finally, we concluded that the enhancement of PC12 axonal extension is due to the magnetic stimulation rather than the mechanical stimulation. Finally, we confirmed that the effectiveness of the uniform AC magnetic field stimulation for the nerve axonal extension using PC12 cells.

Keywords: nerve cell PC12, axonal extension, nerve regeneration, electromagnetic-mechanical stimulation, bioreactor

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Authors: E. Nakamachi, S. Tanaka, K. Yamamoto, Y. Morita

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In this study, we developed a three-dimensional (3D) direct current electric field (DCEF) stimulation bio-reactor for axonal outgrowth enhancement to generate the neural network of the central nervous system (CNS). By using our newly developed 3D DCEF stimulation bio-reactor, we cultured the rat pheochromocytoma cells (PC12) and investigated the effects on the axonal extension enhancement and network generation. Firstly, we designed and fabricated a 3D bio-reactor, which can load DCEF stimulation on PC12 cells embedded in the collagen gel as extracellular environment. The connection between the electrolyte and the medium using salt bridges for DCEF stimulation was introduced to avoid the cell death by the toxicity of metal ion. The distance between the salt bridges was adopted as the design variable to optimize a structure for uniform DCEF stimulation, where the finite element (FE) analyses results were used. Uniform DCEF strength and electric flux vector direction in the PC12 cells embedded in collagen gel were examined through measurements of the fabricated 3D bio-reactor chamber. Measurement results of DCEF strength in the bio-reactor showed a good agreement with FE results. In addition, the perfusion system was attached to maintain pH 7.2 ~ 7.6 of the medium because pH change was caused by DCEF stimulation loading. Secondly, we disseminated PC12 cells in collagen gel and carried out 3D culture. Finally, we measured the morphology of PC12 cell bodies and neurites by the multiphoton excitation fluorescence microscope (MPM). The effectiveness of DCEF stimulation to enhance the axonal outgrowth and the neural network generation was investigated. We confirmed that both an increase of mean axonal length and axogenesis rate of PC12, which have been exposed 5 mV/mm for 6 hours a day for 4 days in the bioreactor. We found following conclusions in our study. 1) Design and fabrication of DCEF stimulation bio-reactor capable of 3D culture nerve cell were completed. A uniform electric field strength of average value of 17 mV/mm within the 1.2% error range was confirmed by using FE analyses, after the structure determination through the optimization process. In addition, we attached a perfusion system capable of suppressing the pH change of the culture solution due to DCEF stimulation loading. 2) Evaluation of DCEF stimulation effects on PC12 cell activity was executed. The 3D culture of PC 12 was carried out adopting the embedding culture method using collagen gel as a scaffold for four days under the condition of 5.0 mV/mm and 10mV/mm. There was a significant effect on the enhancement of axonal extension, as 11.3% increase in an average length, and the increase of axogenesis rate. On the other hand, no effects on the orientation of axon against the DCEF flux direction was observed. Further, the network generation was enhanced to connect longer distance between the target neighbor cells by DCEF stimulation.

Keywords: PC12, DCEF stimulation, 3D bio-reactor, axonal extension, neural network generation

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Authors: Eiji Nakamachi, Ryota Sakiyama, Koji Yamamoto, Yusuke Morita, Hidetoshi Sakamoto

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The regeneration of injured central nerve network caused by the cerebrovascular accidents is difficult, because of poor regeneration capability of central nerve system composed of the brain and the spinal cord. Recently, new regeneration methods such as transplant of nerve cells and supply of nerve nutritional factor were proposed and examined. However, there still remain many problems with the canceration of engrafted cells and so on and it is strongly required to establish an efficacious treating method of a central nerve system. Blackman proposed the electromagnetic stimulation method to enhance the axonal nerve extension. In this study, we try to design and fabricate a new three-dimensional (3D) bio-reactor, which can load a uniform AC magnetic field stimulation on PC12 cells in the extracellular environment for enhancement of an axonal nerve extension and 3D nerve network generation. Simultaneously, we measure the morphology of PC12 cell bodies, axons, and dendrites by the multiphoton excitation fluorescence microscope (MPM) and evaluate the effectiveness of the uniform AC magnetic stimulation to enhance the axonal nerve extension. Firstly, we designed and fabricated the uniform AC magnetic field stimulation bio-reactor. For the AC magnetic stimulation system, we used the laminated silicon steel sheets for a yoke structure of 3D chamber, which had a high magnetic permeability. Next, we adopted the pole piece structure and installed similar specification coils on both sides of the yoke. We searched an optimum pole piece structure using the magnetic field finite element (FE) analyses and the response surface methodology. We confirmed that the optimum 3D chamber structure showed a uniform magnetic flux density in the PC12 cell culture area by using FE analysis. Then, we fabricated the uniform AC magnetic field stimulation bio-reactor by adopting analytically determined specifications, such as the size of chamber and electromagnetic conditions. We confirmed that measurement results of magnetic field in the chamber showed a good agreement with FE results. Secondly, we fabricated a dish, which set inside the uniform AC magnetic field stimulation of bio-reactor. PC12 cells were disseminated with collagen gel and could be 3D cultured in the dish. The collagen gel were poured in the dish. The collagen gel, which had a disk shape of 6 mm diameter and 3mm height, was set on the membrane filter, which was located at 4 mm height from the bottom of dish. The disk was full filled with the culture medium inside the dish. Finally, we evaluated the effectiveness of the uniform AC magnetic field stimulation to enhance the nurve axonal extension. We confirmed that a 6.8 increase in the average axonal extension length of PC12 under the uniform AC magnetic field stimulation at 7 days culture in our bio-reactor, and a 24.7 increase in the maximum axonal extension length. Further, we confirmed that a 60 increase in the number of dendrites of PC12 under the uniform AC magnetic field stimulation. Finally, we confirm the availability of our uniform AC magnetic stimulation bio-reactor for the nerve axonal extension and the nerve network generation.

Keywords: nerve regeneration, axonal extension , PC12 cell, magnetic field, three-dimensional bio-reactor

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Authors: Gabriela T. Nakashima, Elias R. D. Padilla, Joao L. Barros, Gabriela B. Belini, Hiroyuki Yamamoto, Fabio M. Yamaji

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Biochar can be an alternative to use sugarcane trash. Biochar is a solid material obtained from pyrolysis, that is a biomass thermal degradation with low or no O₂ concentration. Pyrolysis transforms the carbon that is commonly found in other organic structures into a carbon with more stability that can resist microbial decomposition. Biochar has a versatility of uses such as soil fertility, carbon sequestration, energy generation, ecological restoration, and soil remediation. Biochar has a great ability to retain water and nutrients in the soil so that this material can improve the efficiency of irrigation and fertilization. The aim of this study was to characterize biochar produced from sugarcane trash in three different pyrolysis temperatures and determine the lowest temperature with the high yield and carbon content. Physical characterization of this biochar was performed to help the evaluation for the best production conditions. Sugarcane (Saccharum officinarum) trash was collected at Corredeira Farm, located in Ibaté, São Paulo State, Brazil. The farm has 800 hectares of planted area with an average yield of 87 t·ha⁻¹. The sugarcane varieties planted on the farm are: RB 855453, RB 867515, RB 855536, SP 803280, SP 813250. Sugarcane trash was dried and crushed into 50 mm pieces. Crucibles and lids were used to settle the sugarcane trash samples. The higher amount of sugarcane trash was added to the crucible to avoid the O₂ concentration. Biochar production was performed in three different pyrolysis temperatures (200°C, 325°C, 450°C) in 2 hours residence time in the muffle furnace. Gravimetric yield of biochar was obtained. Proximate analysis of biochar was done using ASTM E-872 and ABNT NBR 8112. Volatile matter and ash content were calculated by direct weight loss and fixed carbon content calculated by difference. Porosity measurement was evaluated using an automatic gas adsorption device, Autosorb-1, with CO₂ described by Nakatani. Approximately 0.5 g of biochar in 2 mm particle sizes were used for each measurement. Vacuum outgassing was performed as a pre-treatment in different conditions for each biochar temperature. The pore size distribution of micropores was determined using Horváth-Kawazoe method. Biochar presented different colors for each treatment. Biochar - 200°C presented a higher number of pieces with 10mm or more and did not present the dark black color like other treatments after 2 h residence time in muffle furnace. Also, this treatment had the higher content of volatiles and the lower amount of fixed carbon. In porosity analysis, while the temperature treatments increase, the amount of pores also increase. The increase in temperature resulted in a biochar with a better quality. The pores in biochar can help in the soil aeration, adsorption, water retention. Acknowledgment: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil – PROAP-CAPES, PDSE and CAPES - Finance Code 001.

Keywords: proximate analysis, pyrolysis, soil amendment, sugarcane straw

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Authors: Eiji Nakamachi, Tsuyoshi Eguchi, Sayo Yamamoto, Yusuke Morita, H. Sakamoto

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In this study, we aim to reveal the relationship between the meniscal tearing and the articular cartilage injury of knee joint by using the dynamic explicit finite element (FE) method. Meniscal injuries reduce its functional ability and consequently increase the load on the articular cartilage of knee joint. In order to prevent the induction of osteoarthritis (OA) caused by meniscal injuries, many medical treatment techniques, such as artificial meniscus replacement and meniscal regeneration, have been developed. However, it is reported that these treatments are not the comprehensive methods. In order to reveal the fundamental mechanism of OA induction, the mechanical characterization of meniscus under the condition of normal and injured states is carried out by using FE analyses. At first, a FE model of the human knee joint in the case of normal state – ‘intact’ - was constructed by using the magnetron resonance (MR) tomography images and the image construction code, Materialize Mimics. Next, two types of meniscal injury models with the radial tears of medial and lateral menisci were constructed. In FE analyses, the linear elastic constitutive law was adopted for the femur and tibia bones, the visco-hyperelastic constitutive law for the articular cartilage, and the visco-anisotropic hyperelastic constitutive law for the meniscus, respectively. Material properties of articular cartilage and meniscus were identified using the stress-strain curves obtained by our compressive and the tensile tests. The numerical results under the normal walking condition revealed how and where the maximum compressive stress occurred on the articular cartilage. The maximum compressive stress and its occurrence point were varied in the intact and two meniscal tear models. These compressive stress values can be used to establish the threshold value to cause the pathological change for the diagnosis. In this study, FE analyses of knee joint were carried out to reveal the influence of meniscal injuries on the cartilage injury. The following conclusions are obtained. 1. 3D FE model, which consists femur, tibia, articular cartilage and meniscus was constructed based on MR images of human knee joint. The image processing code, Materialize Mimics was used by using the tetrahedral FE elements. 2. Visco-anisotropic hyperelastic constitutive equation was formulated by adopting the generalized Kelvin model. The material properties of meniscus and articular cartilage were determined by curve fitting with experimental results. 3. Stresses on the articular cartilage and menisci were obtained in cases of the intact and two radial tears of medial and lateral menisci. Through comparison with the case of intact knee joint, two tear models show almost same stress value and higher value than the intact one. It was shown that both meniscal tears induce the stress localization in both medial and lateral regions. It is confirmed that our newly developed FE analysis code has a potential to be a new diagnostic system to evaluate the meniscal damage on the articular cartilage through the mechanical functional assessment.

Keywords: finite element analysis, hyperelastic constitutive law, knee joint injury, meniscal tear, stress concentration

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Authors: Anudeep Appe, Bhanu Poluparthi, Lakshmi Kasivajjula, Udai Mv, Sobha Bagadi, Punya Modi, Aditya Singh, Hemanth Gunupudi, Spenser Troiano, Jeff Paul, Justin Stovall, Justin Yamamoto

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The necessity of data-driven decisions in healthcare strategy formulation is rapidly increasing. A reliable framework which helps identify factors impacting a healthcare provider facility or a hospital (from here on termed as facility) market share is of key importance. This pilot study aims at developing a data-driven machine learning-regression framework which aids strategists in formulating key decisions to improve the facility’s market share which in turn impacts in improving the quality of healthcare services. The US (United States) healthcare business is chosen for the study, and the data spanning 60 key facilities in Washington State and about 3 years of historical data is considered. In the current analysis, market share is termed as the ratio of the facility’s encounters to the total encounters among the group of potential competitor facilities. The current study proposes a two-pronged approach of competitor identification and regression approach to evaluate and predict market share, respectively. Leveraged model agnostic technique, SHAP, to quantify the relative importance of features impacting the market share. Typical techniques in literature to quantify the degree of competitiveness among facilities use an empirical method to calculate a competitive factor to interpret the severity of competition. The proposed method identifies a pool of competitors, develops Directed Acyclic Graphs (DAGs) and feature level word vectors, and evaluates the key connected components at the facility level. This technique is robust since its data-driven, which minimizes the bias from empirical techniques. The DAGs factor in partial correlations at various segregations and key demographics of facilities along with a placeholder to factor in various business rules (for ex. quantifying the patient exchanges, provider references, and sister facilities). Identified are the multiple groups of competitors among facilities. Leveraging the competitors' identified developed and fine-tuned Random Forest Regression model to predict the market share. To identify key drivers of market share at an overall level, permutation feature importance of the attributes was calculated. For relative quantification of features at a facility level, incorporated SHAP (SHapley Additive exPlanations), a model agnostic explainer. This helped to identify and rank the attributes at each facility which impacts the market share. This approach proposes an amalgamation of the two popular and efficient modeling practices, viz., machine learning with graphs and tree-based regression techniques to reduce the bias. With these, we helped to drive strategic business decisions.

Keywords: competition, DAGs, facility, healthcare, machine learning, market share, random forest, SHAP

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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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