Search

The structural and dynamical properties of water confined in nanoporous silica with a pore diameter of 2.7 nm were investigated by performing large-scale molecular dynamics simulations using the reactive force field. The radial distribution function and diffusion coefficient of water were calculated, and the values at the center of the pore agreed well with experimental values for real water. In addition, the pore was divided into thin coaxial layers, and the average number of hydrogen bonds, hydrogen bond lifetime, and hydrogen bond strength were calculated as a function of the radial distance from the pore central axis. The analysis showed that hydrogen bonds involving silanol (Si-OH) have a longer lifetime, although the average number of hydrogen bonds per atom does not change from that at the pore center. The longer lifetime, as well as smaller diffusion coefficient, of these hydrogen bonds is attributed to their greater strength.

Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

LETTER TO THE EDITOR

We performed all-atom molecular dynamics simulations for bulk cyclohexane and analysed the short- and medium-range structures in supercooled and glassy states by using the Voronoi tessellation technique. From the analyses of both the potential energy of the system and the radial distribution function of molecules, cyclohexane was found to be vitrified as the temperature decreased. Furthermore, the icosahedral-like structures are dominant at all temperatures and grow in a supercooled liquid, whereas the face-centred cubic structures do not grow when the temperature decreases. It was also ascertained that the icosahedral-like structure is more dominant than the full-icosahedral one. The network of the distorted icosahedron spreads throughout the system at low temperatures. Our simulation demonstrates the stability of the icosahedral structure even in a non-spherical molecule such as cyclohexane., 12 pages, 7 figures

Accumulating evidence suggests that psoriasis is frequently accompanied by metabolic disorders, such as obesity and diabetes. However, the mechanisms underlying the association between increased psoriasis severity and concomitant metabolic syndrome have not been fully clarified. Herein, we show that imiquimod-induced psoriasiform inflammation was exacerbated and prolonged in diabetic obese mice compared to that in control mice, accompanied by remarkably increased lesional expressions of Cxcl5 and Il-1b. Notably, a large number of CXCL5+ Ly6G+ cells infiltrated the dermis and subcutaneous fat tissue of the diabetic obese mice. Most macrophages in the subcutaneous fat tissues of the diabetic obese mice were positive for expression of IL-1β and GRP78/Bip, an endoplasmic reticulum stress marker. Depletion of Ly6G+ cells and macrophages diminished the imiquimod-induced psoriasiform inflammation. Further, CXCL5 potentiated the secretion of IL-1β from macrophages and palmitic acid, a fatty acid released from subcutaneous adipocytes, further enhanced IL-1β secretion via endoplasmic reticulum stress induction. Combined with the fact that the serum levels of both CXCL5 and palmitic acid are significantly elevated in patients with metabolic syndrome, our results suggest a role for CXCL5 and endoplasmic reticulum stress in the increase of psoriasis severity of patients with concomitant metabolic syndrome.

DNA methylation is considered the primary epigenetic mechanism underlying the development of malignant melanoma. Since DNA methylation can be influenced by environmental factors, it is preferable to compare cancer and normal cells from the same patient. In order to compare the methylation status in melanoma tissues and melanocytes from the same individuals, we employed a novel epidermal sheet cultivation technique to isolate normal melanocytes from unaffected sites of melanoma patients. We also analyzed primary and metastatic melanoma samples, three commercially available melanocytes, and four melanoma cell lines. Cluster analysis of DNA methylation data classified freshly isolated melanomas and melanocytes into the same group, whereas the four melanoma cell lines were clustered together in a distant clade. Moreover, our analysis discovered methylation at several novel loci (KRTCAP3, AGAP2, ZNF490), in addition to those identified in previous studies (COL1A2, GPX3); however, the latter two were not observed in fresh melanoma samples. Subsequent studies revealed that NPM2 was hypermethylated and downregulated in melanomas, which was consistent with previous reports. In many normal melanocytes, NPM2 showed distinct immunohistochemical staining, while its expression was lost in malignant melanoma cells. In particular, intraepithelial lesions of malignant melanoma, an important challenge in clinical practice, could be distinguished from benign nevi. The present findings indicate the importance of using fresh melanoma samples, not melanoma cell lines and melanocytes in epigenetic studies. In addition, NPM2 immunoreactivity could be used to differentiate melanomas from normal melanocytes or benign disease.

Diffusion dynamics of topological isomers of polymer molecules was investigated at the single-molecular level in the melt state by employing the fluorophore-incorporated 4-armed star and the corresponding doubly-cyclized, 8-shaped poly(THF) chains. While the single-molecule fluorescence imaging experiment revealed that the diffusion of the 4-armed star polymer was described by a single Gaussian distribution, the diffusion of the 8-shaped polymer exhibited a double Gaussian distribution behaviour. We reasoned that the two 8-shaped polymeric isomers have distinct diffusion modes in the melt state, although ensemble-averaged experimental methods cannot detect differences in the overall conformational state of the isomers. The single-molecule experiments suggested that one of the 8-shaped polymeric isomers, having the horizontally oriented form, causes an efficient threading with the linear matrix chains which leads to slower diffusion compared with the corresponding 4-armed star polymer, while the other 8-shaped polymeric isomer, having the vertically oriented form, displayed faster diffusion by the suppression of effective threading with the linear matrix chains due to its contracted chain conformation.

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare subtype of EBS that is characterized by blistering, mottled pigmentation of the trunk and limbs, punctate hyperkeratosis of the palms and soles, and dystrophic nails.(1) EBS-MP is caused by a mutation in the KRT5 or KRT14 gene encoding keratin 5 (K5) and keratin 14 (K14), respectively.(1, 2) Dermatopathia pigmentosa reticularis (DPR), caused by a KRT14 mutation, is characterized by reticulate pigmentation, noncicatricial alopecia, onychodystrophia and loss of dermatoglyphics.(3) Here, we report cases of EBS-MP with noncicatricial alopecia, a clinical feature of DPR, with a recurrent p.P25L mutation in KRT5 in four Japanese family members. This article is protected by copyright. All rights reserved.

A pair of four-armed star and dicyclic 8-shaped poly(tetrahydrofuran)s, poly(THF)s, possessing a perylene diimide group at the core position (Ia and Ib, respectively) were synthesized by means of an electrostatic self-assembly and covalent fixation (ESA–CF) protocol. Mono- and bifunctional poly(THF)s having N-phenylpiperidinium salt end groups accompanying a perylene diimide tetracarboxylate as a counteranion were prepared by the ion-exchange reaction, and the subsequent covalent conversion by reflux in toluene afforded the corresponding core-fluorescent four-armed star and dicyclic 8-shaped poly(THF)s, (Ia and Ib, respectively) for the use of single-molecule fluorescence microscopy measurements.

Using molecular dynamics (MD) simulation, we simulate the structural change of a telomeric DNA by β-decay of substituted tritium to helium-3. The configuration of the telomeric DNA is obtained by removing TRF2 protein from the TRF2-Dbd-DNA complex (Protein Data Bank ID is 3SJM). We assume that hydrogens (H) of guanines in the telomeric DNA are replaced to helium-3. Since this replacement of the H atoms to the 3He atoms changes the charge distribution significantly, the charge distribution used in the MD simulation for the modified guanine is obtained by the density functional theory calculations. We adopt, as the MD simulation, nanoscale molecular dynamics code with CHARMM36 force field using Langevin thermostat and Nosé–Hoover Langevin piston to control the temperature and pressure of the system, respectively. Moreover, changing both the number of replaced guanine N and the temperature of the system T, we calculate the root mean square deviation RMSD to quantify the dependence of the durability of the telomeric DNA on the β-decays. From the MD simulation, it is found that as N or T becomes larger, the RMSD of the DNA becomes also larger. Namely, it denotes that as the intensity of the β-decays becomes larger or as the temperature is increased, the DNA structure becomes more fragile.

The molecular mechanism through which how beta decays in tritium-substituted species damage DNA and polymeric materials is still unknown. Molecular dynamics simulations of hydrogen-removed polyethylene were performed to predict the structural change of the polyethylene chain after the substituted tritium decays. We calculated the potential energy, the global orientational order parameter, and the average number of consecutive trans bonds. The results are that, the greater the number of removed hydrogen atoms, the higher the potential energy and the lower the value of the global orientational order parameter and the average number of consecutive trans bonds. Thus, after losing hydrogen, polyethylene becomes poorer in terms of both thermal and structural stabilities.

Hopping dynamics in glass has been known for quite a long time. In contrast, hopping dynamics in smectic-A (SmA) and hexatic smectic-B (HexB) liquid crystals (LC) has been observed only recently. The hopping in SmA phase occurs among the smectic layers (one-dimensionally), while hopping in HexB phase occurs inside the layers (two-dimensionally). The hopping dynamics in SmA and HexB liquid crystal phases is investigated by parallel soft-core spherocylinders, while three-dimensional hopping dynamics in inherent glassy states is investigated by systems of Weeks–Chandler–Andersen (WCA) spheres. The temperature dependence of diffusion coefficients of hopping in SmA phase can be described by the Arrhenius equation characteristic of activation process. In HexB LC phase, the diffusion coefficients saturate at higher temperatures. In a system of WCA spheres, the values and temperature dependence of diffusion coefficients depend on the observed states.

A thermal display, a type of haptic display, is effective for providing intuitive information about temperature. In many thermal display studies, users have assumed sitting positions when using these devices. However, their use in a large-scale virtual-reality system requires users to be in a standing position, as they generally observe three-dimensional (3D) objects while standing or walking around. Thus, we developed thermal displays that are suitable for large-scale virtual-reality systems. From another standpoint, in scientific visualization, response time is very important for observing physical phenomena, especially for dynamic numerical simulation. One way to optimize this parameter is to provide two types of thermal information: the rate of thermal change, and the actual temperature. To this end, we propose a bracelet-shaped thermal display with three Peltier elements that can provide both types of information. Finally, we present an example of visualizing and haptizing the result of a molecular dynamics simulation.

The differences in the structure formations of a single polyethylene (PE) chain in united atom molecular dynamics (UAMD) simulations under quenching was investigated with varying force fields (FFs) that included torsional potential. We estimated the crystallinity of the folded structures undergoing local crystallization of the single PE chain. In simulations with DREIDING FF, highly folded structures were observed with fast quenching at the rate of 50 K/ns. From the viewpoint of crystallinity, we clarified that it was easy to achieve folding of the PE chains into local crystals with DREIDING FFs. With recent commonly used general FFs such as OPLS-UA and TraPPE-UA, highly folded structures were observed by quenching at the rate of 1 K/5 ns. In the present paper, we examine the Rigby–Roe (RR) FF optimized by Theodorou and coworkers and Paul–Yoon–Smith (PYS) FF optimized by Rutledge and coworkers. With the RR-Theodorou and PYS-Rutledge FFs, crystallization was observed with quenching at 1 K/ns and 1 K/5 ns, respectively. Consequently, it was relatively easier to achieve folding with the RR-Theodorou FF than with the PYS-Rutledge, OPLS-UA, and TraPPE-UA FFs.The differences in the structure formations of a single polyethylene (PE) chain in united atom molecular dynamics (UAMD) simulations under quenching was investigated with varying force fields (FFs) that included torsional potential. We estimated the crystallinity of the folded structures undergoing local crystallization of the single PE chain. In simulations with DREIDING FF, highly folded structures were observed with fast quenching at the rate of 50 K/ns. From the viewpoint of crystallinity, we clarified that it was easy to achieve folding of the PE chains into local crystals with DREIDING FFs. With recent commonly used general FFs such as OPLS-UA and TraPPE-UA, highly folded structures were observed by quenching at the rate of 1 K/5 ns. In the present paper, we examine the Rigby–Roe (RR) FF optimized by Theodorou and coworkers and Paul–Yoon–Smith (PYS) FF optimized by Rutledge and coworkers. With the RR-Theodorou and PYS-Rutledge FFs, crystallization was observed with quenching at 1 K/ns and 1 K/5 ns, ...

The self-assembly of dissolved symmetric bolaamphiphilic molecules is studied using dissipative particle dynamics simulations. Specifically, we investigate how interactions between the dual hydrophilic ends of the molecules affect the self-assembly process. Simulations show that four types of self-assembled structures (spherical micelles, tubes, vesicles, and wormlike micelles) are obtained from a random configuration of symmetric bolaamphiphilic molecules in solution. We find that the self-assembled structures change from spherical micelles to tubes, then to vesicles, and finally to wormlike micelles as the repulsive interactions between the hydrophilic ends increase. The molecular shapes in vesicles tend to be more rodlike than those in spherical micelles, tubes, or wormlike micelles.

The micelle formation in amphiphilic solution is investigated by molecular dynamics (MD) simulation of coarse-grained rigid amphiphiles with explicit solvent molecules. In our simulation model, the intensity of the hydrophilic interaction and the hydrophobic interaction can be varied independently. Our simulations show that various kinds of micellar structures are formed at a lower temperature by quenching from a random configuration of amphiphilic molecules in solution at a higher temperature. The micellar shape changes from a disc (bilayer) into a cylinder and then into a sphere as the intensity of the hydrophilic interaction increases. It is also found that the micelle formation proceeds in a stepwise fashion through the coalescence of smaller micelles. From the analysis of the orientational order for the amphiphilic molecules, it is concluded that the orientational order parameters can be used to distinguish the micellar shapes clearly.

68歳男性。2003年5月中旬より右腎部に腫瘤を自覚し, 右鼠径部にリンパ節が腫脹してきたので2003年6月23日当科を受診した。初診時3.4×3.7cm大で弾性硬の紅褐色皮下腫瘤を呈し, 生検にてメルケル細胞癌と診断した。2003年7月30日広範囲切除, 右鼠径・外腸骨リンパ節郭清術を施行し, 右鼠径部リンパ節転移を認めたため, 術後放射線療法を追加した。その後再発転移なく経過したが, 2005年4月血清NSE値が上昇し, CT上で多発肝転移像を認めた。エトポシド・シスプラチン療法は効果なく, シクロフォスファミド・ドキソルビシン・ビンクリスチン療法が著効し, 一旦CRとなった。しかし, 10月に肝転移が再発し, 胸腔内転移も認め, アムルビシンを投与するも効果なく, 2005年12月永眠された。多発肝転移を来した症例で, 化学療法の選択に難渋した。

鎖状高分子系の構造形成シュミレーション, 中村 浩章［核融合科学研究所 理論・シュミレーション研究センター］藤原 進［京都工芸繊維大学 繊維学部 高分子学科］佐藤 哲也［独立行政法人 海洋研究開発機構 地球シュミレーションセンター］＊所属は当時のものを記載

It was reported, in our previous works, that two orientationally ordered domains of short chain molecules move collectively as if they were rigid bodies in spite of the non-bonded short-range interaction potential (Lennard–Jones potential) among chain molecules. In this paper, in order to investigate the rigidity of the domain of short chain molecules in further detail, molecular dynamics simulations are performed for the following four case combinations of domains: the case I, II, III and IV are (61+29), (61+61), (124+61) and (124+124) chain molecule combinations, respectively. From these simulations, the size dependence of the domains' motion is demonstrated. Estimating an oscillation period τ for each case, it is found that τ (61,29)≃ τ (61,61) τ (124,61) τ (124,124). This relation is a peculiar property of orientationally ordered domains in a short chain-molecule system.

Structure formation of a single polymer chain with 500 methylene groups is investigated by means of a molecular dynamics simulation. We find that the folded orientationally ordered structure is formed at a low temperature by gradual stepwise cooling or by quenching from a random configuration at a higher temperature. It is also found that the global orientational order grows in a gradual manner in the case of gradual stepwise cooling, whereas it grows in a stepwise manner in the case of quenching.

高分子鎖の構造形成の分子動力学シミュレーション, 藤原進［核融合科学研究所］＊所属は当時のものを記載

Previous studies have shown that the antitumor effects of OX40 agonists depend on the immunogenicity of the tumor and that poorly immunogenic tumors such as B16F10 melanomas do not respond to OX40 agonist treatment. In this study, we have shown that intratumoral CD4 + T lymphodepletion sensitized poorly immunogenic B16F10 melanomas to immunotherapy with an OX40 agonist. CD4 + T lymphodepletion dramatically altered the tumor immune microenvironment, making it more susceptible to the antitumor effects of an OX40 agonist by enhancing the accumulation of CD8 + T cells and natural killer (NK) cells in tumor tissue. However, unexpectedly, the number of CD11b + Gr-1 + myeloid-derived suppressor cells (MDSCs) within tumor tissues also significantly increased as a result of CD4 + T lymphodepletion. As a countermeasure against CD8 + T-cell accumulation, CCR2-positive CD11b + Gr-1 int (monocytic) MDSCs predominantly increased. Treatment with an OX40 agonist under CD4 + T lymphodepletion neither reduced MDSCs nor increased CD8 + T cells and NK cells, but further enhanced the expression of cytotoxic molecules from tumor-infiltrating effector cells. Our results suggest that combined immunotherapy using both an OX40 agonist and CD4 + T lymphodepletion could be a promising therapeutic strategy for poorly immunogenic tumors and might be more effective if further combined with a therapeutic strategy targeting MDSCs.

An investigation was conducted to ascertain the sound pressure levels of home electric appliances in actual situations, what the ideal levels were, and the level considered to be unacceptable. Added to this, the question of what amount purchasers considered it reasonable to pay for noise reduction. It was found that impression of the “actual, ” “ideal” and “intolerable” levels of sounds from home electric appliances could be obtained by psychoacoustical experiments. The results showed that there was a uniform difference of about 10dB between the three levels for the sounds used in the experiment. Subjects also suggested the acceptable cost of noise reduction in home electric appliances. Interesting information was also obtained concerning what kinds of electric appliances housewives wanted to have, what performance they expected, and what factors might contribute to the selection of electric appliances.

The self-assembly of flexible bolaamphiphilic molecules in a solution is studied by dissipative particle dynamics simulations. In particular, we investigate the effect of the interaction difference, Δa, between the two different hydrophilic end groups on the self-assembly in a bolaamphiphilic solution. Our simulations show that two types of self-assembled structures, spherical vesicles and worm-like micelles, are obtained from a random configuration of bolaamphiphilic molecules in a solution. We find that the worm-like micelles are formed when Δa > 0, whereas spherical vesicles are obtained when Δa ≤ 0. It is also ascertained that the size of the spherical vesicles decreases as Δa decreases.

This study aims to create an interface for visualizing numerical data on a head-mounted display (HMD) and introduce functions to allow control of this visualization via hand gestures. HMDs have the advantage of providing a user with a 360-degree field of view without taking up a lot of space. However, it is difficult to control visualized numerical data intuitively with this type of display because the user cannot see his/her own hand. We therefore introduced functions allowing the user to control the virtual scene with visualized virtual hands. We developed a system in which a virtual menu is presented to the users and they can change the visualization method by pushing virtual panels. The user can move freely in the visualized virtual scene. Moreover, to help users share their thoughts, we have introduced a drawing function that enables users to indicate points and areas of interest in the visualized scene.

A method for the selection of appropriate test case, an important issue for conformance testing of protocol implementations as well as software engineering, is presented. Called the partial W-method, it is shown to have general applicability, full fault-detection power, and yields shorter test suites than the W-method. Various other issues that have an impact on the selection of a suitable test suite including the consideration of interaction parameters, various test architectures for protocol testing and the fact that many specifications do not satisfy the assumptions made by most test selection methods (such as complete definition, a correctly implemented reset function, a limited number of states in the implementation, and determinism), are discussed. >

The phase behavior of bolaamphiphilic solutions is studied by coarse-grained molecular dynamics simulations of semiflexible bolaamphiphilic molecules with explicit solvent molecules. Our simulations show that six kinds of self-assembled structures (spherical micelles, worm-like micelles, bicontinuous structure, hexagonal structure, plate-like micelles, and lamellar structure) are obtained. It is established that, at low concentrations, a plate-like micelle changes to worm-like micelles, and then to spherical micelles as the hydrophilic interaction increases. Conversely, at intermediate concentrations, a lamellar structure changes to a bicontinuous structure; it then changes to worm-like micelles or a hexagonal structure as the hydrophilic interaction increases. It is also observed that the global orientational order parameter for the end bonds of bolaamphiphilic molecules can be used to clearly distinguish between the randomly-oriented structures (the spherical micelles, the worm-like micelles, and the bicontinuous structure), the lamellar structure, the hexagonal structure, and the plate-like micelles.

This paper describes an innovative technique, the gradient pattern analysis (GPA), for analysing spatially extended dynamics. The measures obtained from GPA are based on the spatio-temporal correlations between large and small amplitude fluctuations of the structure represented as a dynamical gradient pattern. By means of four gradient moments it is possible to quantify the relative fluctuations and scaling coherence at a dynamical numerical lattice and this is a set of proper measures of the pattern complexity and equilibrium. The GPA technique is applied for the first time in 3D-simulated molecular chains with the objective of characterizing small symmetry breaking, amplitude and phase disorder due to spatio-temporal fluctuations driven by the spatially extended dynamics of a relaxation regime.

The micellar shape transition in amphiphilic solutions is studied by coarse-grained molecular dynamics simulations of rigid amphiphilic molecules with explicit solvent molecules. Our simulations show that the dominant micellar shape changes from disc to cylinder, and then to sphere as the hydrophilic interaction increases. We find that, as the hydrophilic interaction increases, the potential energy decreases monotonically even during the micellar shape transition, whereas the slope of the potential energy decreases in a stepwise manner in relation to the micellar shape transition. We also ascertained that there exists a wide coexistence region in the intensity of the hydrophilic interaction between a cylinder and a sphere, whereas the coexistence region between a cylinder and a disc is very narrow.

By molecular dynamics simulation, discovered is a strange rigid-like nature for a hexagonally packed domain of short chain molecules. In spite of the non-bonded short-range interaction potential (Lennard-Jones potential) among chain molecules, the packed domain gives rise to a resultant global moment of inertia. Accordingly, as two domains encounter obliquely, they rotate so as to be parallel to each other keeping their overall structures as if they were rigid bodies., Comment: 7 pages, 5 figures, and 2 tables