Calmodulin (CaM) demonstrates biologically critical regulation of Ca_V1-2 Ca²⁺ channels. This talk explores three aspects of the powerful Ca²⁺ decoding that CaM exhibits in this context. (1) We summarize the current model of CaM/channel modulation, wherein Ca²⁺-free CaM (apoCaM) preassociates with channels, and subsequent Ca²⁺ influx drives conformational changes that induce regulation. Ca²⁺ binding to the individual lobes of CaM autonomously trigger different forms of modulation. The N-lobe usually responds to Ca²⁺ entry through sources other than the channel being regulated (global Ca²⁺ preference); the C-lobe favors Ca²⁺ entering via the regulated channel itself (local Ca²⁺ preference). (2) We describe a novel module that transforms the local/global Ca²⁺ preference of regulation. This module furnishes a vital clue (or '

Rosetta

stone') for Ca²⁺ decoding. To start, Ca_V2.2 channels exhibit N-lobe Ca²⁺-dependent inactivation (CDI) with a global Ca²⁺ preference. Switching a small segment of Ca_V1.2 or Ca_V1.3 into Ca_V2.2 produces chimeric channels where CDI now has a local preference. Conversely, Ca_V1.3 channels exhibit an N-lobe CDI with a local preference, and deletion of this same portion within Ca_V1. 3 switches the Ca²⁺ preference from local to global. The key element of this module is a Ca²⁺/CaM binding site. (3) This module implicates a simple decoding mechanism wherein Ca²⁺ preference is specified by the ratio of channel affinities for Ca²⁺/CaM versus apoCaM. Indeed, the transforming actions of the CaM-binding module satisfy stringent predictions of this new mechanism. [J Physiol Sci. 2007;57 Suppl:S14]

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Common human diseases and drug response are complex traits that involve entire networks of changes at the molecular level driven by genetic and environmental perturbations. Efforts to elucidate disease and drug response traits have focused on single dimensions of the system. Studies focused on identifying changes in DNA that correlate with changes in disease or drug response traits, changes in gene expression that correlate with disease or drug response traits, or changes in other molecular traits (e. g., metabolite, methylation status, protein phosphorylation status, and so on) that correlate with disease or drug response are fairly routine and have met with great success in many cases. However, to further our understanding of the complex network of molecular and cellular changes that impact disease risk, disease progression, severity, and drug response, these multiple dimensions must be considered together. Here I present an approach for integrating a diversity of molecular and clinical trait data to uncover models that predict complex system behavior. By integrating diverse types of data on a large scale I demonstrate that some forms of common human diseases are most likely the result of perturbations to specific gene networks that in turn causes changes in the states of other gene networks both within and between tissues that drive biological processes associated with disease. These models elucidate not only primary drivers of disease and drug response, but they provide a context within which to interpret biological function, beyond what could be achieved by looking at one dimension alone. That some forms of common human diseases are the result of complex interactions among networks has significant implications for drug discovery: designing drugs or drug combinations to impact entire network states rather than designing drugs that target specific disease associated genes.

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　近年，歯科治療において患者の口腔内の審美性に対する要求が高まっているが，天然歯に近似した色調，光透過性の再現は，歯科医師や歯科技工士の経験によるところが大きい．そのため，コンピュータシミュレーションを用い，光の振る舞いを定量的に解析することが可能となれば，より審美性の高い歯科治療を行うための多くの知見を得ることができる．これまで我々は，光線追跡シミュレーションに必要な各種歯科材料の光学特性の測定を行った．

　本研究では，実際に歯冠補綴装置（二ケイ酸リチウムガラスセラミックス)と支台築造体（コア用レジン，金属）を製作し，人工太陽灯を照射した際の輝度の測定を行った．そして，照明設計解析ソフトウェア上で実験1と同様の状況を再現し，輝度のシミュレーションを行い，実測と比較した．

　その結果，同一試料内で部位による明度差（ΔL*）が認められ，切縁－中央でΔL*は大きい傾向を示した．シミュレーションの結果，中央，歯頸部では実測よりも低い値となったが，近似した傾向を示した．本研究で行った光線追跡シミュレーションは，歯冠補綴治療における光の現象を解析するために有用であるものと考えられた．

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To compare full and partial coverage crowns made with different CAD/CAM leucite reinforced ceramic blocks on fracture resistance and fractographic analysis. Full coverage and partial coverage crowns with finish line at 2 mm and 4 mm above the gingiva for molars made with IPS Empress CAD and

BM. After fatigue process, the fracture test and fractographic analysis were conducted. Although the fracture resistance of IPS Empress crowns did not show any statistical differences regardless of the design, both the partial coverage crowns fabricated using BM showed significantly higher load at break and peak load than the full coverage crown. The crowns made with IPS Empress showed significantly higher fracture resistance than that made with BM, regardless of the restorative design. The fracture resistance and fractographic analysis of CAD/CAM leucite reinforced full and partial coverage crowns were influenced by the restorative design of and material type.

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Interplanetary spacecraft require precise predictions of their trajectory for achieving their mission targeting requirements. For the purpose of precise navigation, the detailed modeling of all small forces affecting the spacecraft’s orbital motion is necessary. The dominating small forces on an interplanetary trajectory are planetary gravity perturbations and Solar Radiation Pressure. In addition to these traditional perturbations, the Thermal Radiation Pressure induced by the spacecraft surfaces can be an appreciable small force. This study focuses on the precise thermal analysis of the external surfaces by using a numerical Finite Element Method on three actual ESA interplanetary spacecraft, i.e. , Mars Express, and Venus Express. This paper also presents the evaluations of the accelerations due to the Thermal Radiation Pressure.

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  Many models to assess the impact of agricultural activities for the environment have been developed recently. And the accurate soil characteristics are important in applying these models. However, measuring the all soil characteristics costs and takes long time and is not efficient. Therefore, many models have pedotransfer functions (PTFs). It was confirmed that the performance of the PTFs depends strongly on the data that has been used for the development of the PTFs. So, in this study, we examined influences of the bulk density for the retention curve and the hydraulic conductivity of Shimajiri maji soil at first, and applied the PTFs (

) to evaluate the practicality. As a result, it was confirmed that there were some errors in applying the to estimate the retention curve of the Shimajiri maji soil.

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107P/4015 Wilson-Harrington is one of the most intriguing objects, being known for having a cometary history as well as Near Earth Object characteristics, which could answer questions regarding both the origin of life and formation and evolution of small bodies. We first briefly summarize the knowledge state of this small body, leading to its actual classification. We then look at its main dynamical characteristics to prepare for a near future rendezvous and sampling mission, and we make comparisons between the target of the mission, 67P/Churyumov-Gerasimenko, for which the spacecraft is carrying a lander, and the targets of Hayabusa and of the Hayabusa Follow-on Mission, Itokawa and 1999 JU3. Finally, we investigate the local stability properties in both proximity of the target and on the surface, and show simulations, to discuss approach strategies.

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The world's first solar sail IKAROS (Interplanetary Kite-craft Accelerated by Radiation of the Sun) was launched along with the Venus Climate Orbiter Akatsuki in May 2010. At the time of writing, IKAROS is still the only solar sail in deep space. IKAROS was full successful of missions that have been planned for first half year. After the Venus flyby in Dec 2010, it carried out an extended mission. IKAROS has succeeded many additional engineering and scientific missions. On the orbit determination, we obtained various skills. IKAROS has been almost 8 years from launch, we have been still maintaining operation that repeating the power generation period and hibernation period cycle for 10 months and more. Even though we cannot be obtained enough observation data for orbit determination that can withstand long-term propagation over several years. But we have been successful in four times search operation, at the wake-up from the hibernation in 2012-2015. As a similar success,

has been successfully wake-up from hibernation for 31-month form June 2011 to January 2014 due to a power shortage. In that operation, the antenna pointing accuracy was not a problem at all. However, IKAROS has an area to mass ratio which is 50 times that of , and the solar distance of IKAROS's orbit is only a fraction of one. So, it has been received several hundred times of solar radiation pressure. Therefore, we needed high precision attitude dynamic model for predicting future position of IKAROS. We have been 3 years from when we got receiving the last observation data in 2015. We studied extension of attitude motion model and optimizations for model parameter. The base of attitude motion model, was constructed using nominal phase of data and modified for the first wake up from hibernation. Then, the attitude motion model was divided 3 sections, by spin rate for search operation after 2015. And the attitude motion model parameters were estimated using one of the devised optimization method. In this paper, we present modified attitude motion model for solar angle-free and the optimized attitude motion model parameter.

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Cyprinid herpesvirus 3 (CyHV-3), also named koi herpesvirus (KHV), is a lethal pathogen of koi and common carp Cyprinus carpio. In the present study, we described a procedure to generate monoclonal antibodies (mAbs) against the envelope protein pORF132 of CyHV-3 and application of the mAb. Three recombinant plasmids targeting the expression of one complete pORF132 and two truncated pORF132 were constructed, respectively. After induction, a truncated pORF132 was successfully expressed in a soluble form and the purified recombinant protein was used in the preparation of mAbs. Two hybridoma cell clones, 4E11 and 4B11, were obtained and mAb 4E11 reacted to CyHV-3 infected cells and not to CyHV-2 (goldfish hematopoietic necrosis virus) and IcHV-1 (channel catfish virus) infected cells. An antigen-capture ELISA based on the pair of mAb 4E11 and anti-CyHV-3 IgY was primarily constructed. This antigen-capture ELISA could distinguish between the CyHV-3 infected and uninfected fish samples.

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A novel assay system, based on the bi-molecular fluorescence complementation （BiFC） technique in Escherichia coli, was developed for detecting transient interactions such as those between kinases and their substrates. BiFC is an alternative technique for detecting protein-protein associations in live cells. This system detected, the interaction between OsMEK1 and its direct target, OsMAP1. By contrast, BiFC fluorescence was not observed when OsMAP2 or OsMAP3, which are not substrates of OsMEK1, were used as prey proteins. We also screened for interacting proteins of Ca²⁺-dependent protein kinase 8 （OsCPK8）, a regulator of plant immune responses, and identified three proteins as interacting molecules of OsCPK8. The interaction between OsCPK8 and two of these proteins （ARF-GEF and peptidyl prolyl isomerase） was confirmed in rice cells by means of BiFC technology. These results indicate that our new assay system has the potential to screen for protein kinase target molecules.

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Toxicity is a major cause of failure in drug development. A toxicogenomic approach may provide a powerful tool for better assessing the potential toxicity of drug candidates. Several approaches have been reported for predicting hepatotoxicity based on reference compounds with well-studied toxicity mechanisms. We developed a new approach for assessing compound-induced liver injury without prior knowledge of a compound's mechanism of toxicity. Using samples from rodents treated with 49 known liver toxins and 10 compounds without known liver toxicity, we derived a hepatotoxicity score as a single quantitative measurement for assessing the degree of induced liver damage. Combining the sensitivity of the hepatotoxicity score and the power of a machine learning algorithm, we then built a model to predict compound-induced liver injury based on 212 expression profiles. As estimated in an independent data set of 54 expression profiles, the built model predicted compound-induced liver damage with 90.9% sensitivity and 88.4% specificity. Our findings illustrate the feasibility of ab initio estimation of liver toxicity based on transcriptional profiles.

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Objective: The aim of the study is to reduce related symptoms of stomachache to meet the need for expert systems of Traditional Chinese Medicine which included different TCM specialist diagnostic experiences and least core symptoms using Rough Sets theory. Methods: Based on Rough Sets models,

is combination with the heuristic search algorithm allows core attributes selection and determination. The research used

Rosetta

to reduce symptoms based on 18 decision tables according to TCM syndrome differentiation theory. Results: We achieved 18 reduction symptoms sets for each syndrome differentiation of TCM and 30 core symptoms of stomachache based on Rough Sets theory and 279 TCM diagnosis cases. Conclusion: As an important concept of Rough Sets theory, attributes reduction provides “the most valuable symptoms” for different TCM stomachache syndromes. It is useful to attempt a kind of approach with good mathematical performance to reduce redundant symptoms for TCM syndrome differentiation.

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A new subsurface sampling device is proposed for use in small-body exploration. The device proposed has a multi-stage telescopic structure that is extended into regolith using high-pressure gas. High-pressure gas is also used to collect the sample. Since the device proposed has no actuator, it is expected to be highly reliable. We experimentally demonstrated that this device can excavate a dummy regolith layer up to a depth of 1 m and collect sufficient samples located deeper than 1 m for in-situ analysis. These results indicate that the device proposed is a viable candidate for actual exploration missions.

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The advent of antibody therapy has brought about a change in the treatment of diseases. The efficacy of antibody modeling relies on the intricate atomic interactions between antibodies and antigens. Traditional methods for determining antibody structures, such as X-ray crystallography, are costly and time-consuming. Computational docking offers a faster and more cost-effective approach to obtaining complex antibody and antigen complexes even in challenging scenarios.

, a widely employed software for protein structure modeling, incorporates a scoring function specifically tailored for modeling antibody-antigen interactions. The unique characteristics of the antibody-antigen interface can result in inaccurate predictions. Therefore, it is essential to understand the existing scoring function and the behavior of the antibody-antigen interface. In this study, we evaluated specific parameters within -derived scoring functions, with a particular focus on the energy landscape of the structures they generated. We found that performance in antibody-antigen docking simulations could be enhanced by omitting parameters related to solvation. Also, we delved into the physico-chemical properties of antibody-antigen interfaces, paying special attention to the complementarity-determining regions and epitopes. Our exploration helped identify certain parameters that significantly influence docking simulation performance. These insights pave the way for the creation of more accurate scoring functions tailored for specific antibody-antigen interactions.

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The cellulose binding domain (CBD) of cellulosome-integrating protein A from Clostridium thermocellum NBRC 103400 was genetically fused to FMN-dependent NADH-azoreductase (AZR) and glucose 1-dehydrogenase (GDH) from Bacillus subtilis. The fusion enzymes, AZR-CBD and CBD-GDH, were expressed in Escherichia coli

-gami B (DE3). The enzymes were purified from cell-free extracts, and the specific activity of AZR-CBD was 15.1 U/mg and that of CBD-GDH was 22.6 U/mg. AZR-CBD and CBD-GDH bound strongly to 0.5 % swollen cellulose at approximately 95 and 98 % of the initial protein amounts, respectively. After immobilization onto the swollen cellulose, AZR-CBD and CBD-GDH retained their catalytic activity. Both enzymes bound weakly to 0.5 % microcrystalline cellulose, but the addition of a high concentration of microcrystalline cellulose (10 %) improved the binding rate of both enzymes. A reactor for flow injection analysis was filled with microcrystalline cellulose-immobilized AZR-CBD and CBD-GDH. This flow injection analysis system was successfully applied for the determination of glucose, and a linear calibration curve was observed in the range of approximately 0.16–2.5 mM glucose, with a correlation coefficient, r, of 0.998.

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