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We developed the object-oriented class library "YLO" to study molecular structures. YLO is written in C++ and composed of a set of classes, which are a kind of program units, resembling subroutines in Fortran. Each class performs a certain job independently in a whole program. YLO deals with non-organic, organic molecules and biological macromolecules. The coordinate file of a molecule is read / written in PDB format. Using the YLO library, one can make various types of application programs efficiently, such as Monte Carlo simulator, Genetic Algorithm optimizer and so on.

Perforated pipe is an essential component in contemporary automotive mufflers, since such a pipe reduces the acoustic power of the flow noise, which is significantly influenced by its velocity. Nonuniformly perforated pipes, the orifices of which are arranged in a belt configuration, are widely used in muffler systems. The resonance of such perforated pipe when located inside the elliptic cavity is investigated experimentally in this paper. The results obtained are also compared with the predictions of our method of theoretical analysis for a uniformly perforated pipe in order to clarify the resonance mechanism. It was found that the difference between the measured and theoretical values is less than 5 Hz for a short pipe. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 85(7): 22–28, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.1104

We report the implementation of an atomistic Brownian dynamics simulation of proteins. A protein was described by united-atom model with AMBER91 force field. The solvent was treated by distance-dependent dielectric/surface area model. The computation time of the Brownian dynamics and the calculated results on structure and dynamics of 28-mer ββα fold peptide with the implicit solvent model were compared with those of molecular dynamics simulation with explicit solvent. The Brownian dynamics simulation was 53 times faster than molecular dynamics simulation with explicit solvent. The simulation was stable and the artifacts often observed in simulations at vacuum condition were reduced. The results indicate that the Brownian dynamics with the implicit solvent model can be widely used in studies of protein dynamics by long time simulation in future.

Perforated pipes are frequently used to attenuate exhaust noise in contemporary automotive mufflers. Resonances at a particular frequency, however, may exceed the overall acoustic reduction effect of the muffler when the shape and fixing position are inappropriate. The theoretical calculations of the sound pressure inside the elliptical perforated tube muffler are carried out by solving the wave equation. The resonance mechanism of the perforated tube muffler is analyzed. The results of the analyses have been confirmed by experiments. © 2000 Scripta Technica, Electron Comm Jpn Pt 3, 83(8): 51-60, 2000

The interiors of all living cells are highly crowded with macromolecules, which results in a considerable difference between the thermodynamics and kinetics of biological reactions in vivo from that in vitro. To begin to elucidate the principles of intermolecular dynamics in the crowded environment of cells, employing Brownian dynamics (BD) simulations, we examined possible mechanism(s) responsible for the great reduction in diffusion constants of macromolecules in vivo from that at infinite dilution. In an E. coli cytoplasm modelcomprised of 15 different macromolecule types at physiological concentrations, where macromolecules were represented by spheres with their Stokes radii, BD simulations were performed with and without hydrodynamic interactions (HI). Without HI, the calculated diffusion constant of green fluorescent protein (GFP) is much larger than experiment. On the other hand, when HI were considered, the in vivo experimental GFP diffusion constant is almost reproduced without adjustable parameters. In addition, HI give rise to significant, size independent intermolecular dynamic correlations. These results suggest that HI play an important role on macromolecular dynamics in vivo.

A new tripodal ligand with an asymmetric carbon atom, Ph2PCH2CH(Me)N(CH2CH2PPh2)2 (S-mnp3) was prepared using L-alanine as an optically active starting material; a series of its complexes, [M(X)(S-mnp3)]BPh4(M = Ni(II) and Co(II); X = NCS−, Cl−, Br− and I−) was prepared. Electronic spectra of these complexes indicated that their coordination geometries are essentially the same as those of corresponding complexes containing the tripodal ligand tris (diphenylphosphinoethyl) amine. Thus, all the present nickel complexes in solution exhibit electronic spectra typical of trigonal-bipyramidal complexes of diamagnetic configuration. CD spectra of these nickel complexes have been discussed on the basis of the selection rules for magnetic dipole transitions under C 3v symmetry. Cobalt(II) complexes are either high-spin or low-spin, depending on the nature of the unidentate ligand. The high-spin cobalt(II) complexes did not show CD spectra typical of trigonal-bipyramidal geometry.

Some organs in animals display left-right (LR) asymmetry. To better understand LR asymmetric morphogenesis in Drosophila, we studied LR directional rotation of the hindgut epithelial tube. Hindgut epithelial cells adopt a LR asymmetric (chiral) cell shape within their plane, and we refer to this cell behavior as planar cell-shape chirality (PCC). Drosophila E-cadherin (DE-Cad) is distributed to cell boundaries with LR asymmetry, which is responsible for the PCC formation. Myosin ID switches the LR polarity found in PCC and in DE-Cad distribution, which coincides with the direction of rotation. An in silico simulation showed that PCC is sufficient to induce the directional rotation of this tissue. Thus, the intrinsic chirality of epithelial cells in vivo is an underlying mechanism for LR asymmetric tissue morphogenesis.

Asp187 and Gln190 were predicted as conserved and closely located at the Na(+) binding site in a topology and homology model structure of Na(+)/proline symporter (PutP) of Escherichia coli. The replacement of Asp187 with Ala or Leu did not affect proline transport activity; whereas, change to Gln abolished the active transport. The binding affinity for Na(+) or proline of these mutants was similar to that of wild-type (WT) PutP. This result indicates Asp187 to be responsible for active transport of proline without affecting the binding. Replacement of Gln190 with Ala, Asn, Asp, Leu and Glu had no effect on transport or binding, suggesting that it may not have a role in the transport. However, in the negative D187Q mutant, a second mutation, of Gln190 to Glu or Leu, restored 46 or 7% of the transport activity of WT, respectively, while mutation to Ala, Asn or Asp had no effect. Thus, side chain at position 190 has a crucial role in suppressing the functional defect of the D187Q mutant. We conclude that Asp187 is responsible for transport activity instead of coupling-ion binding by constituting the translocation pathway of the ion and Gln190 provides a suppressing mutation site to regain PutP functional activity.

The interiors of all living cells are highly crowded with macromolecules, which differs considerably the thermodynamics and kinetics of biological reactions between in vivo and in vitro. For example, the diffusion of green fluorescent protein (GFP) in E. coli is ~10-fold slower than in dilute conditions. In this study, we performed Brownian dynamics (BD) simulations of rigid macromolecules in a crowded environment mimicking the cytosol of E. coli to study the motions of macromolecules. The simulation systems contained 35 70S ribosomes, 750 glycolytic enzymes, 75 GFPs, and 392 tRNAs in a 100 nm × 100 nm × 100 nm simulation box, where the macromolecules were represented by rigid-objects of one bead per amino acid or four beads per nucleotide models. Diffusion tensors of these molecules in dilute solutions were estimated by using a hydrodynamic theory to take into account the diffusion anisotropy of arbitrary shaped objects in the BD simulations. BD simulations of the system where each macromolecule is represented by its Stokes radius were also performed for comparison. Excluded volume effects greatly reduce the mobility of molecules in crowded environments for both molecular-shaped and equivalent sphere systems. Additionally, there were no significant differences in the reduction of diffusivity over the entire range of molecular size between two systems. However, the reduction in diffusion of GFP in these systems was still 4–5 times larger than for the in vivo experiment. We will discuss other plausible factors that might cause the large reduction in diffusion in vivo.

Eight new cobalt(III) complexes of the type, [CoX3(mmtp)]n+ (mmtp = 1,1,1-tris(dimethylphosphinomethyl)ethane, X3 = (Cl)3, (Br)3, (CN)3, (NH3)3, mmtp, 3-azapentane-1,5-diamine (dien), 1,4,7-triazacyclononane (tacn), and 1,4,7-trithiacyclononane (ttcn)), were prepared and characterized. All of the complexes are stable in the solid state, but the halogeno complexes aquate rapidly in water, and the ammonia complex liberates NH3 slowly in 1 mol dm−3 HCl to give [CoCl2(NH3)(mmtp)]+, other complexes including [Co(mmtp)2]3+ being stable in solution. The crystal structure of [Co(mmtp)2][Co(CN)6]·2.25H2O was determined by X-ray analysis. Crystal data: orthorhombic, space group Pca21, a = 31.579(5), b = 10.521(1), c = 23.458(3) A, V = 7794(2) A3, Z= 8, R = 0.084 for 4196 reflections. The Co–P bond distances are 2.291(9)–2.357(7) A (av 2.331 A), which are appreciably longer than those usually found in Co(III)–phosphine complexes. The absorption spectra of the complexes were compared with one another and with those o...

WL-O系統,WL-B系統及び内在性ウイルス遺伝子の部分発現のある個体群の3群を用いて,内在性ウイルス遺伝子と細胞表面レセプター遺伝子が鶏染色体上でどういう位置関係にあるのかを後代検定法を用いて調査した。その結果,gs抗原とchf活性の分離比はそれぞれの遺伝子座が同一染色体上にある場合の期待値に近く,我々は,少なくとも一対のgag遺伝子とenv遺伝子が同一染色体上にあるものと結論した。そして,これらの遺伝子は,ev-3遺伝子座のGsとgsの対立遺伝子と同じ性質のものであろうと推定した。一方,B亜群ウイルスに対する細胞の感受性と,gs抗原及びchf活性の分離比については,両座位が独立の場合の期待分離比に近いので,B亜群ウイルスに対する細胞のレセプター遺伝子座とこの内在性ウイルス遺伝子座とは異なる染色体上にあるものと思われた。

鶏白血病ウイルス(ALV)抗体測定法としての酵素抗体法(ELISA)について抗原抗体反応系の解析を行い,さらに血清中和法(SN),蛍光抗体法(FA)との相関関係と感度の比較を行った。1)A亜群,B亜群2種の抗原に対する抗体価の推移をELISA,SN,FAで確認すると,ELISA,FAでは主として群特異抗体(gs抗体)を,SNは亜群特異抗体を検出していると思われた。2)gs抗体を産生する抗原成分として3種の蛋白が確認された。そして,それぞれに対する抗体の発現順序は,まずp27,つぎにgp85,さらにp15に対する抗体であった。3)1野外鶏群について,3種の測定方法で算出した抗体価の関係を見ると,いずれにも相関が認められた。4)測定方法による検出感度を比較すると,ELISAは,SNの約10倍,FAはSNとほぼ同感度であった。

Object. The “wearing-off” phenomenon often hampers the treatment of Parkinson disease (PD). Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to ameliorate the wearing-off phenomenon, the mechanism by which it does this remains unclear. As part of an inquiry into the mechanism of STN DBS, the authors measured synaptic dopamine levels in the striatum by performing positron emission tomography (PET) with [11C]raclopride. Methods. Three patients with PD who were experiencing the wearing-off phenomenon underwent PET scanning before and after DBS of the STN. The clinical features in these patients were evaluated by applying the Hoehn and Yahr, United Parkinson's Disease Rating, and Schwab and England Activities of Daily Living Scales. Before and after surgery, PET scans were obtained using [11C]raclopride prior to and 1 hour following an oral administration of levodopa. Regions of interest for the [11C]raclopride binding potential (RacloBP) were set in the bilateral putamen and the caudate nucleus. All clinical scores were dramatically improved postoperatively. Deep brain stimulation of the STN reduced the baseline RacloBP in both the putamen and caudate nucleus, but the differences between the pre- and postoperative levels were insignificant. Before DBS of the STN, the levodopa administration significantly reduced RacloBP in the putamen (p < 0.0001). Postoperatively the drug-induced reduction in RacloBP became statistically insignificant. The drug-induced increase in synaptic dopamine concentrations in the putamen preoperatively was estimated to be approximately four times higher than that after surgery (p < 0.01). The drug-induced RacloBP change in the caudate nucleus was similar to that in the putamen, although the magnitude of the change was lower (p < 0.005). The drug-induced increase in the caudate nucleus was also reduced postoperatively (p < 0.05). Conclusions. Deep brain stimulation of the STN induces the stabilization of synaptic dopamine concentrations in the striatum and may attribute to the alleviation of levodopa-related motor fluctuations.

BACKGROUND Although transurethral resection of a bladder tumor (TUR-Bt) alone has been standard treatment for single superficial bladder carcinoma, some authors reported a certain prophylactic effect of a single immediate intravesical instillation of chemotherapeutic agent after TUR-Bt. A prospective randomized study was conducted to determine whether a single (2″R)-4′-O-tetrahydropyranyl-doxorubicin (THP) instillation immediately after TUR-Bt is beneficial to patients with a single superficial bladder carcinoma. METHODS One hundred seventy patients with a single resectable superficial bladder carcinoma (Ta-1, primary or recurrent with no recurrence during the last 1 year) were enrolled in this study. THP (30 mg/30 mL of normal saline) was administered into the bladder within 6 hours after TUR-Bt in arm A, while TUR-Bt alone was done in arm B. RESULTS Of the 170 patients, 160 (94.1%) were eligible and were followed up for a median time of 40.8 months. There was a significant difference in the recurrence free curve between the 2 arms (log-rank test; P = 0.0026), with 92.4% recurrence free rate at 1 year, 82.7% at 2 years, and 78.8% at 3 years in arm A (84 patients) and 67.0%, 55.7%, and 52.6%, respectively, in arm B. The recurrence rate per year was 0.11 ± 0.22 in arm A and 0.24 ± 0.36 in arm B, with a significant difference (P = 0.007). Toxicity included pain with micturition in 9 patients (10.7%), urinary frequency/urgency in 5 patients (6.0%), and macroscopic hematuria in 7 patients (8.3%). CONCLUSIONS These data indicate that a single THP instillation immediately after TUR reduces the recurrence of superficial bladder carcinoma. Cancer 2002;94:2363–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10496

Hydrodynamic interactions play an important role in the dynamics of macromolecules. The most common way to take into account hydrodynamic effects in molecular simulations is in the context of a brownian dynamics simulation. However, the calculation of correlated brownian noise vectors in these simulations is computationally very demanding and alternative methods are desirable. This paper studies methods based on Krylov subspaces for computing brownian noise vectors. These methods are related to Chebyshev polynomial approximations, but do not require eigenvalue estimates. We show that only low accuracy is required in the brownian noise vectors to accurately compute values of dynamic and static properties of polymer and monodisperse suspension models. With this level of accuracy, the computational time of Krylov subspace methods scales very nearly as O(N(2)) for the number of particles N up to 10 000, which was the limit tested. The performance of the Krylov subspace methods, especially the "block" version, is slightly better than that of the Chebyshev method, even without taking into account the additional cost of eigenvalue estimates required by the latter. Furthermore, at N = 10,000, the Krylov subspace method is 13 times faster than the exact Cholesky method. Thus, Krylov subspace methods are recommended for performing large-scale brownian dynamics simulations with hydrodynamic interactions.

Self-organization is one of the most fundamental phenomena in biology. Elucidating the mechanisms of the self-assembly of biological molecules, such as protein folding/binding and formation of lipid bilayer membranes, have been a fascinating topic over decades in biological field. Hydrodynamic interactions (HIs) give rise to collective motions between molecules. Therefore, they may play an important role on dynamics of self-assembly. Although there are significant advances in theoretical and computational studies on thermodynamics and kinetics of self-assembling systems recent years, analysis on effects of HIs to the reactions are limited due to their high complexity. Here, by using a Brownian dynamics (BD) simulation technique, we evaluate the importance of HIs on kinetic of self-assembly in a set of examples, formation of lipid membrane and actin polymerization reaction. We first built coarse-grained models of lipid and actin monomer. A cluster of lipid molecules was represented by two particles, one is hydrophilic head group and the other is hydrophobic tail group, and attractive interaction between tail groups was applied. For actin polymerization system, each monomer was represented by two particles and an angle-dependent attractive interaction was applied to form long filaments. In BD simulations, the Rotne-Prager-Yamakawa tensor was used to account for HIs between particles. In the early stage of self-assembly, HIs between inter-monomer particles decelerated the association rate of monomers to form oligomers compared with that in the simulations without inter-monomer HIs in both systems. On the other hand, the HIs accelerate the reaction of oligomers to form a fully-assembled state or much longer polymers. This phenomenon could be explained by the Kirkwood-Riseman theory. Those results clearly suggest that HIs greatly affect kinetics of self-assembly reactions and considering the interactions is crucial for studying dynamics of biological systems.

In order to demonstrate that the extracorporeal shockwave lithotripsy (ESWL) for urolithiasis causes a renal damage, we immunoassayed S100a0 protein and creatine kinase isozymes (CK-B & CK-M) in the serum and urine from patients with renal stone (N = 21) and those with ureteral stone (N = 18) before and after ESWL. S100a0 protein and CK-B, which are localized in the proximal renal tubules at relatively high concentrations, were enhanced more or less both in the urine and serum samples after the treatment in both groups of patients. Since CK-M, which is mainly localized in muscle tissue, also increased in both groups of patients, S100a0 protein and CK-B may be derived not only from kidney, but also from muscle tissues.

The presence of chick helper factor (chf) in chick embryo fibroblasts (CEF) which lack the natural group-specific (gs) antigen of avian leukosis was determined in a simple Mendelian manner from the dominant autosomal gene. The presence or absence of chf determined the susceptibility to subgroup E virus in the WL-O line, but not in the WL-B line, which had the fixed C/BE character. Dimethyl sulfoxide (DMSO) together with BH-RSV(RAV-7) promoted the appearance of chf in gs − chf − CEF after long-term culture.