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To evaluate the effect of various rotational motions on the torque/force generation, surface wear, and shaping ability of the ProGlider glide path instrument (Dentsply Sirona).Mesiobuccal and mesiolingual canals of mandibular molars were selected based on the canal volume, length, angle of curvature (25°-40°), and radius of curvature (4-8 mm) after micro-computed tomographic scanning. The samples were randomly assigned to four groups (n = 13, each) according to movement kinematics [continuous rotation (CR; 300 rpm), optimum torque reverse motion (OTR; 180° forward and 90° reverse when torque0.4 N cm), time-dependent reciprocal motion (TmR; 180° forward and 90° reverse), and optimal glide path motion (OGP; a combination of 90° forward, 90° reverse, 90° forward, and 120° reverse)]. Instrumentation was performed with an automated root canal instrument and torque/force analysing device. Maximum torque/force values, canal volume changes, and canal-centring ratios at 1, 3, 5, and 7 mm were evaluated. Surface defects (pits, grooves, microcracks, blunt cutting edges, and disruption of cutting edges) and spiral distortion on the ProGlider instrument were scored at the tip and 5 mm short of the tip before and after five consecutive uses with scanning electron microscopy. The Kruskal-Wallis test followed by Dunn's post-test with Bonferroni correction and Wilcoxon signed-rank test were used to analyse the data (α = 0.05).Optimal glide path motion generated significantly less clockwise torque and greater upward force than other groups (p .05). OGP resulted in significantly fewer surface defects than CR (p .05). In OGP and CR, the tip exhibited more surface defects than 5 mm short of the tip (p .05). CR resulted in greater volume changes than OGP and TmR (p .05) and greater centring ratios (i.e., more deviation) than OGP at 1 mm and OTR at 3 mm (p .05).Under laboratory conditions using the ProGlider instrument, OGP generated significantly less clockwise torque and greater upward force than the other rotatory motions. OGP generated fewer superficial defects than CR, and the three modes of reciprocal rotation better maintained the apical curvature of root canals than CR with the ProGlider instrument.

Purpose To investigate the risk of debonding of resin-bonded fixed dental prosthesis frameworks and the effects on the periodontal tissue in patients with reduced alveolar bone levels. Materials & methods The abutment teeth were the upper central incisor and the canine. Resin-bonded fixed dental prosthesis framework fabricated using zirconia was set to models with five different alveolar bone levels. A 200-N load (the maximum clenching force of the anterior teeth) was applied to the center of the pontic to analyze the internal stress on the framework, adhesive cement, and periodontal tissue using finite element analysis. Results The mean maximum principal stress generated in the framework was 25.33 and 29.35 MPa in the models with the normal and the lowest alveolar bone level, respectively. Regarding shear stress on the adhesive cement, stress concentration was observed on the connector side in all models, and it increased on the cervical side of the central incisor as the alveolar bone level decreased. In addition, the mean maximum and minimum principal strains generated on the periodontal ligament of the central incisor and canine tended to increase as alveolar bone loss progressed. Furthermore, the mean maximum principal stress on the cortical bone was the greatest in the model with the most significant bone loss at 5.10 MPa. Conclusions This study suggested that the risk of debonding and periodontal tissue damage might be higher when resin-bonded fixed dental prosthesis frameworks were used in patients with reduced alveolar bone levels compared to those in a healthy state. This article is protected by copyright. All rights reserved.

This study aimed to evaluate the surface strain at the cervical area of endodontically treated molars with a large pulp chamber restored using a composite resin core with three different types of core build-up systems.Reproduction models of human mandibular molars with prepared post spaces were used in this study. Roots duplicated with a composite resin were used as the experimental teeth. Three types of core build-up systems were used: composite resin core(RC), composite resin core with fiber posts (FC), and composite resin core with a prefabricated zirconia tube (ZC). Each group comprised eight specimens. Crowns made of yttria partially stabilized zirconia were cemented with dual-cure resin cement. Four strain gauges were attached to the surfaces of each specimen: the cervical area of the root and crown, on the buccal and lingual sides. The surface strain at each cervical area was measured using a static loading test and statistically analyzed.In the case of static loading to the buccal cusp inner slope, ZC showed a significantly lower strain than RC in the crown on the buccal side and in the root and FC in the root. In the central fossa, ZC showed a significantly lower strain than FC in the root on the lingual side.The prefabricated zirconia tube reduced the surface strain at the cervical area of the buccal/lingual root in molars; however, the effect was small in the cervical area of the crown.

The biological functions of proteins are traditionally thought to depend on well-defined three-dimensional structures, but many experimental studies have shown that disordered regions lacking fixed three-dimensional structures also have crucial biological roles. In some of these regions, disorder–order transitions are also involved in various biological processes, such as protein-protein interaction and ligand binding. Therefore, it is crucial to study disordered regions and structural transitions for further understanding of protein functions and folding. Owing to the costs and time requirements of experimental identification of natively disordered or transitional regions, the development of effective computational methods is a key research goal. In this study, we used overall residue dependencies and deep representation learning for prediction and reused the obtained disordered regions for the prediction of disorder–order transitions. Two similar and related prediction tasks were combined. Firstly, we developed a novel deep learning method, Res-BiLstm, for residue-wise disordered region prediction. Our method outperformed other predictors with respect to almost all criteria, as evaluated using an independent test set. For disorder-order transition prediction, we proposed a transfer learning method, Res-BiLstm-NN, with an acceptable but unbalanced performance, yielding reasonable results. To grasp underlining biophysical principles of disorder-order transitions, we performed qualitative analyses on the obtained results and discovered that most transitions have strong disordered or ordered preferences, and more transitions are consistent with the ordered state than the disordered state, different from conventional wisdom. To the best of our knowledge, this is the first sizable-scale study of transition prediction.Availabilityhttps://github.com/Yanzziang/Transition_Disorder_PredictionContactkengo@ecei.tohoku.ac.jp

Frustrated phagocytosis is critical for crystal-associated fibrosis and cancer. Of note, multi-walled carbon nanotubes (MWCNTs), the highly representative products of nanotechnology, induce macrophage NLRP3 inflammasome activation and cause asbestosis-like pathogenesis. However, it remains largely unknown how macrophages efficiently recognize MWCNTs on their cell surfaces. Here we identify by a targeted screening of phagocyte receptors the phosphatidylserine receptors T-cell immunoglobulin mucin 4 (Tim4) and Tim1 as the pattern-recognition receptors for carbon crystals. Docking simulation studies revealed spatiotemporally stable interfaces between aromatic residues in the extracellular IgV domain of Tim4 and one-dimensional carbon crystals. Further, CRISPR/Cas9-mediated deletion of Tim4 and Tim1 revealed that Tim4, but not Tim1, critically contributed to recognition of MWCNTs by peritoneal macrophages and to granuloma development in a mouse model of direct mesothelium exposure to MWCNTs. These results suggest that Tim4 recognizes MWCNTs through aromatic interactions and mediates frustrated phagocytosis leading to granulomas.

Purpose To investigate stress and strain concentrations on resin-bonded fixed dental prostheses (RBFDPs) frameworks of different design using finite element analysis. Methods A human dry skull was scanned and models were produced using three-dimensional printer. After abutment preparation, three frameworks, including a three-unit RBFDP, and two-unit cantilevered RBFDPs using #21 and #23 for the abutment tooth, were fabricated. Scanned data were subtracted to define boundary of each structure. Occlusal force (200N) was loaded at 45° to long axis of the pontic. The distributions of shear stress and principal strain in the RBFDP models were measured to evaluate the risk for framework-debonding from the abutment teeth and the impact on periodontal tissue. Results The percentage voxels with shear stress >11MPa in adhesive cement layer of three-unit RBFDP using #21 and #23 were 4.16% and 2.25%, respectively; in two-unit cantilevered RBFDPs, it was 19.25% using #21, and 23.4% using #23. The maximum principal strain on periodontal ligaments in two-unit cantilevered RBFDPs using #21 was the largest, and smallest in the three-unit RBFDP. The maximum principal strain in framework was largest in the two-unit cantilevered RBFDP using #23, and smallest in the three-unit RBFDP. Conclusions The risk for framework-debonding in three-unit RBFDPs was substantially lower than that in two-unit RBFDPs. In difficult cases with indication for three-unit RBFDPs, two-unit cantilever design using the canine would be more advantageous for preservation of periodontal tissue, while for risk of framework-debonding, the design using the central incisor would be more advantageous.

Background N-terminal acetylation is one of the most common protein modifications in eukaryotes and occurs co-translationally when the N-terminus of the nascent polypeptide is still attached to the ribosome. This modification has been shown to be involved in a wide range of biological phenomena such as protein half-life regulation, protein-protein and protein-membrane interactions, and protein subcellular localization. Thus, accurately predicting which proteins receive an acetyl group based on their protein sequence is expected to facilitate the functional study of this modification. As the occurrence of N-terminal acetylation strongly depends on the context of protein sequences, attempts to understand the sequence determinants of N-terminal acetylation were conducted initially by simply examining the N-terminal sequences of many acetylated and unacetylated proteins and more recently by machine learning approaches. However, a complete understanding of the sequence determinants of this modification remains to be elucidated. Results We obtained curated N-terminally acetylated and unacetylated sequences from the UniProt database and employed a decision tree algorithm to identify the sequence determinants of N-terminal acetylation for proteins whose initiator methionine (iMet) residues have been removed. The results suggested that the main determinants of N-terminal acetylation are contained within the first five residues following iMet and that the first and second positions are the most important discriminator for the occurrence of this phenomenon. The results also indicated the existence of position-specific preferred and inhibitory residues that determine the occurrence of N-terminal acetylation. The developed predictor software, termed NT-AcPredictor, accurately predicted the N-terminal acetylation, with an overall performance comparable or superior to those of preceding predictors incorporating machine learning algorithms. Conclusion Our machine learning approach based on a decision tree algorithm successfully provided several sequence determinants of N-terminal acetylation for proteins lacking iMet, some of which have not previously been described. Although these sequence determinants remain insufficient to comprehensively predict the occurrence of this modification, indicating that further work on this topic is still required, the developed predictor, NT-AcPredictor, can be used to predict N-terminal acetylation with an accuracy of more than 80%. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1699-4) contains supplementary material, which is available to authorized users.

Hyperventilation is a well-known risk factor of ischemic events in pediatric patients with moyamoya disease. For young children, it is important to avoid crying to prevent ischemic events because of their unstable postoperative hemodynamics. To prevent crying in pediatric patients, we used dexmedetomidine(DEX)for sedation immediately after revascularization surgery.We investigated the effects of postoperative DEX use on hemodynamic changes and the avoidance of crying and hypocapnia in pediatric patients with moyamoya disease.Ten consecutive patients(5 boys and 5 girls)who underwent surgical revascularization were enrolled, and 16 hemispheres(8 boys and 8 girls)were sedated with DEX postoperatively between August 2011 and August 2016.During extubation after revascularization, DEX was started at 0.4μg/kg/hr under spontaneous breathing and its dose was increased depending on the degree of consciousness, to maintain sedation of at least 3 on the Ramsay scale. DEX administration was terminated the next morning.Sedation was maintained well in all patients without hypocapnia, and no ischemic complications were observed. One patient cried and needed additional intravenous DEX injections and was immediately re-sedated;no hypocapnia developed. Respiratory depression did not occur and changes in respiratory rate and decreases in SpODexmedetomidine is safe and useful for postoperative sedation in children with moyamoya disease.

Summary Macrophage recognition and phagocytosis of crystals is critical for the associated fibrosis and cancer. Of note, multi-walled carbon nanotubes (MWCNTs), the highly representative products of nanotechnology, induce macrophage NLRP3 inflammasome activation and cause asbestosis-like pathogenesis. However, it remains largely unknown how macrophages efficiently recognize MWCNTs on their cell surfaces. Here, we identify by a targeted screening of phagocyte receptors the phosphatidylserine receptors T cell immunoglobulin mucin 4 (Tim4) and Tim1 as the pattern-recognition receptors for carbon crystals. Docking simulation studies reveal spatiotemporally stable interfaces between aromatic residues in the extracellular IgV domain of Tim4 and one-dimensional carbon crystals. Further, CRISPR-Cas9-mediated deletion of Tim4 and Tim1 reveals that Tim4, but not Tim1, critically contributes to the recognition of MWCNTs by peritoneal macrophages and to granuloma development in a mouse model of direct mesothelium exposure to MWCNTs. These results suggest that Tim4 recognizes MWCNTs through aromatic interactions and mediates phagocytosis leading to granulomas.

NLDB (Natural Ligand DataBase; URL: http://nldb.hgc.jp ) is a database of automatically collected and predicted 3D protein–ligand interactions for the enzymatic reactions of metabolic pathways registered in KEGG. Structural information about these reactions is important for studying the molecular functions of enzymes, however a large number of the 3D interactions are still unknown. Therefore, in order to complement such missing information, we predicted protein–ligand complex structures, and constructed a database of the 3D interactions in reactions. NLDB provides three different types of data resources; the natural complexes are experimentally determined protein–ligand complex structures in PDB, the analog complexes are predicted based on known protein structures in a complex with a similar ligand, and the ab initio complexes are predicted by docking simulations. In addition, NLDB shows the known polymorphisms found in human genome on protein structures. The database has a flexible search function based on various types of keywords, and an enrichment analysis function based on a set of KEGG compound IDs. NLDB will be a valuable resource for experimental biologists studying protein–ligand interactions in specific reactions, and for theoretical researchers wishing to undertake more precise simulations of interactions.

Duplication of the alimentary tract is a rare congenital malformation that occurs most often in the abdominal region, whereas esophageal duplication cyst develops typically in the thoracic region but occasionally in the neck and abdominal regions. Esophageal duplication cyst is usually diagnosed in early childhood because of symptoms related to bleeding, infection, and displacement of tissue surrounding the lesion. We recently encountered a rare adult case of esophageal duplication cyst in the abdominal esophagus. A 50-year-old man underwent gastroscopy, endoscopic ultrasonography, computed tomography, and magnetic resonance imaging to investigate epigastric pain and dysphagia that started 3 months earlier. Imaging findings suggested esophageal duplication cyst, and the patient underwent laparoscopic resection followed by intraoperative esophagoscopy to reconstruct the esophagus safely and effectively. Histopathological examination of the resected specimen revealed two layers of smooth muscle in the cystic wall, confirming the diagnosis of esophageal duplication cyst.

Poly(N-isopropylacrylamide) (PNIPAM) nanoparticles were prepared by precipitation polymerization using atom transfer radical polymerization (ATRP) in aqueous media at 45 °C, which is above the lower critical solution temperature (LCST). Nanoparticles were coated on a quartz resonator and their HCl gas-sensing properties were measured by a quartz crystal microbalance (QCM) technique. PNIPAM nanoparticles adsorbed HCl gas reversibly, while PNIPAM thin film showed partly irreversible adsorption. Furthermore, for PNIPAM nanoparticles, the gas adsorption/desorption properties, such as adsorption time and reversibility, were not influenced by the mass loaded on the quartz resonator, which indicated that these properties were derived from the sum of the properties of each individual nanoparticle. The QCM-based PNIPAM nanoparticle sensor showed excellent reproducibility and the sensitivity to 1 ppm of HCl was approximately 3.8 Hz/ppm.

We propose a fast clustering and reranking method, CyClus, for protein–protein docking decoys. This method enables comprehensive clustering of whole decoys generated by rigid-body docking using cylindrical approximation of the protein–proteininterface and hierarchical clustering procedures. We demonstrate the clustering and reranking of 54,000 decoy structures generated by ZDOCK for each complex within a few minutes. After parameter tuning for the test set in ZDOCK benchmark 2.0 with the ZDOCK and ZRANK scoring functions, blind tests for the incremental data in ZDOCK benchmark 3.0 and 4.0 were conducted. CyClus successfully generated smaller subsets of decoys containing near-native decoys. For example, the number of decoys required to create subsets containing near-native decoys with 80% probability was reduced from 22% to 50% of the number required in the original ZDOCK. Although specific ZDOCK and ZRANK results were demonstrated, the CyClus algorithm was designed to be more general and can be applied to a wide range of decoys and scoring functions by adjusting just two parameters, p and T. CyClus results were also compared to those from ClusPro. Proteins 2013; © 2012 Wiley Periodicals, Inc.

This study evaluated the fracture strength and mode of failure of structurally compromised teeth with flared root canals restored using composite resin with four different systems.Sixty endodontically treated bovine teeth were uniformly shaped to simulate human mandibular premolars with flared root canals. The roots were divided into four groups of 15 specimens each based on the type of restoration: composite resin core only (control), glass fiber post, cylindroid glass fiber ribbons, and glass fiber post and ribbons. All specimens were loaded until fracture occurred using a universal testing machine. Average fracture loads were compared with a one-way ANOVA and Tukey HSD test (α=.05). The modes of failure were observed and the Fisher exact test and Bonferroni correction were used for statistical analysis.The fiber post and ribbon group (1035.70N) and the fiber ribbon group (881.77N) showed significantly higher fracture strength than the controls (567.97N) (p.05). The fiber post and ribbon group also showed significantly higher fracture strength than the fiber post group (769.40N). Almost all specimens showed unrestorable root fractures (p.008). The control group had a significantly higher ratio of core sectional fractures (p.017).Cylindroid glass fiber ribbons significantly increased the fracture strength of the composite resin post and cores in the case of the dentin within the thin root canal wall. Based on the results, this study recommends the combined use of glass fiber post and ribbons.

Life science research now heavily relies on all sorts of databases for genome sequences, transcription, protein three-dimensional (3D) structures, protein-protein interactions, phenotypes and so forth. The knowledge accumulated by all the omics research is so vast that a computer-aided search of data is now a prerequisite for starting a new study. In addition, a combinatory search throughout these databases has a chance to extract new ideas and new hypotheses that can be examined by wet-lab experiments. By virtually integrating the related databases on the Internet, we have built a new web application that facilitates life science researchers for retrieving experts' knowledge stored in the databases and for building a new hypothesis of the research target. This web application, named VaProS, puts stress on the interconnection between the functional information of genome sequences and protein 3D structures, such as structural effect of the gene mutation. In this manuscript, we present the notion of VaProS, the databases and tools that can be accessed without any knowledge of database locations and data formats, and the power of search exemplified in quest of the molecular mechanisms of lysosomal storage disease. VaProS can be freely accessed at http://p4d-info.nig.ac.jp/vapros/ .

The chromodomain of HP1α binds directly to lysine 9-methylated histone H3 (H3K9me). This interaction is enhanced by phosphorylation of serine residues in the N-terminal tail of HP1α by unknown mechanism. Here we show that phosphorylation modulates flexibility of HP1α’s N-terminal tail, which strengthens the interaction with H3. NMR analysis of HP1α’s chromodomain with N-terminal tail reveals that phosphorylation does not change the overall tertiary structure, but apparently reduces the tail dynamics. Small angle X-ray scattering confirms that phosphorylation contributes to extending HP1α’s N-terminal tail. Systematic analysis using deletion mutants and replica exchange molecular dynamics simulations indicate that the phosphorylated serines and following acidic segment behave like an extended string and dynamically bind to H3 basic residues; without phosphorylation, the most N-terminal basic segment of HP1α inhibits interaction of the acidic segment with H3. Thus, the dynamic string-like behavior of HP1α’s N-terminal tail underlies the enhancement in H3 binding due to phosphorylation.

Purpose The purpose of this study was to evaluate the influence of water immersion on the mechanical properties of three kinds of glass fiber posts and the fracture resistance of structures using resin composites with glass fiber posts. Methods Each post was divided into three groups; a control group and two water immersion groups (30 and 90 days). Flexural strength was determined by three-point bending test. Each structure was divided into two groups; a control group and a water immersion group for 30 days. The fracture strength of structures was determined by a static loading test. Results In the flexural strength, two kinds of post in water immersion groups showed lower values than control groups. In the fracture strength, two kinds of structures in water immersion group showed lower values than control groups. Conclusion The prefabricated glass fiber posts and structures using resin composites with glass fiber posts were affected by water immersion.

Coupling between proteins motion and ligand binding can be well explained by the linear response theory (Ikeguchi, M.; Ueno, J.; Sato, M.; Kidera, A. Phys Rev Lett 2005, 94, 078102.), in which the structural change is treated as a response to ligand binding. The prediction accuracy of structural change upon ligand binding has been improved by replacing the variables in the linear response theory from Cartesian coordinates to dihedral angles. The dihedral angle theory can more accurately describe the rotational motions of protein domains compared with the Cartesian theory, which tends to shift the coordinate to the tangential direction of the domain rotation. In this study, the ligand-bound form of Ferric-binding protein was predicted from its ligand-free form using the dihedral linear response theory. When the variance-covariance matrix, the key component in the linear response theory, was derived by linear conversion from Cartesian coordinates to dihedral angles, the dihedral linear response theory gave an improvement in the prediction. Therefore, the description of the rotational motion by dihedral angles is crucial for accurate prediction of protein structural change.

Perioperative management of pancreaticoduodenectomy (PD) is a constant dilemma and challenging for gastrointestinal surgeons. Postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE) are of particular concern, and the onset of these conditions indicates a prolonged postoperative stay (POS). The procedure and postoperative outcomes of pancreaticojejunostomy performed at our hospital are reported.POPF, DGE, and POS were investigated in 54 patients who had undergone PD at our hospital since June 2007. Pancreaticojejunal end-to-side anastomosis using the invagination method without a stenting tube and without duct-to-mucosa anastomosis was performed in all patients, regardless of pancreatic duct diameter.There were 26 patients (48.2%) without POPF, 24 (44.4%) with grade A, 4 (7.4%) with grade B, and none with grade C. The mean POS was 28.3 days. DGE was observed in 4 patients (7.4%) who underwent pylorus-preserving PD (PpPD). There were 34 patients with a soft pancreas. None of the patients experienced intraperitoneal bleeding or abscess, and no surgery-related deaths occurred.The reconstructive pancreaticojejunostomy procedure performed at our hospital appears to be safe and convenient, and we plan to collect additional data, including assessments of the function of the remaining pancreas, in the future.

As a part of the studies conducted by the Pharma SNPs Consortium (PSC), the enzyme activities of CYP1A2, CYP2A6 and CYP2B6 variants with altered amino acids as a result of single nucleotide polymorphisms (SNPs) found among the Japanese population were analyzed under a unified protocol using the same lots of reagents by the laboratories participating in the PSC. Mutations in CYP1A2, CYP2A6 and CYP2B6 were introduced by site-directed mutagenesis and the wild type and mutated CYP molecules were expressed in Escherichia coli. The expressed cytochrome P450s were purified and the enzyme activities were measured in reconstitution systems. CYP1A2 and CYP1A2Gln478His did not show any differences in 7-ethoxyresorufin O-deethylase activity. CYP2A6 and CYP2A6Glu419Asp metabolized coumarin to form 7-hydroxycoumarin in a similar manner, whereas CYP2A6Ile471Thr showed low activity compared to the wild-type CYP2A6. CYP2B6, CYP2B6Pro167Ala and CYP2B6Arg487Cys showed the same activity for 7-ethoxy-4-triflouromethyl-coumarin O-deethylation. However, CYP2B6Gln172His was roughly twice as active as CYP2B6 and the other CYP2B6 variants for 7-ethoxy-4-triflouromethylcoumarin O-deethylation activity. Although higher inter- and intra-laboratory variations were observed for the calculated Km and V(max) values because the studies were conducted in several different laboratories, the degree of variations was reduced by the increased number of analyses and the adoption of a simple analysis system.

The aim of the present study was to evaluate the fracture load and fracture mode of thin Ceria-stabilized tetragonal zirconia polycrystals/Al(2)O(3 )nanocomposites (Ce-TZP/A) and Yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) crown frameworks. Artificial maxillary second premolars were prepared for metal-ceramic crown and all-ceramic crown restorations and Co-Cr tooth analogs were duplicated. 10 standard (0.5 mm overall thickness) zirconia-ceramic crown frameworks (Y-TZPs) for all-ceramic crown preparation and 10 modified (a 0.3-mm-thick framework increased in thickness by adding a 1.0-mm-thick palatal margin with a height of 2.0 mm) zirconia-ceramic crown frameworks (Y-TZPm, Ce-TZP/Am) for metal-ceramic crown preparation were fabricated. The frameworks were cemented to the Co-Cr tooth analog and loaded vertically until fracture. The fracture load of Y-TZPs (180.0 N) and Ce-TZP/Am (183.7 N) were significantly higher than that of Y-TZPm (133.7 N). There was a significant difference in fracture mode between Y-TZPm and Ce-TZP/Am. Within the limitation of this study, Ce-TZP/Am provide sufficient strength for clinical application.

We propose a fast clustering and reranking method, CyClus, for protein-protein docking decoys. This method enables comprehensive clustering of whole decoys generated by rigid-body docking using cylindrical approximation of the protein-proteininterface and hierarchical clustering procedures. We demonstrate the clustering and reranking of 54,000 decoy structures generated by ZDOCK for each complex within a few minutes. After parameter tuning for the test set in ZDOCK benchmark 2.0 with the ZDOCK and ZRANK scoring functions, blind tests for the incremental data in ZDOCK benchmark 3.0 and 4.0 were conducted. CyClus successfully generated smaller subsets of decoys containing near-native decoys. For example, the number of decoys required to create subsets containing near-native decoys with 80% probability was reduced from 22% to 50% of the number required in the original ZDOCK. Although specific ZDOCK and ZRANK results were demonstrated, the CyClus algorithm was designed to be more general and can be applied to a wide range of decoys and scoring functions by adjusting just two parameters, p and T. CyClus results were also compared to those from ClusPro.

ヤイトバナより paederoside (Pa), paederosidic acid (Paa) ならびに scandoside (Sca) のイリドイド配糖体3化合物を単離した。これら化合物の生理活性を評価するために, ヤエムグラ種子より既に単離されている asperuloside (Asp) と deacetyl asperulosidic acid (Daa) ならびにDaaより誘導した deacetyl asperuloside (Da) を供試して比較検討した (Fig. 1)。その結果, ラクトン環をもつPaでは顕著な生長抑制を示すが, ラクトン環が開環しているPaaでは活性が低下し, Paaの脱アセチル体であるScaでは活性が著しく弱く, レタス幼苗に対しては, 伸長促進作用を示した。またこれらの結果は, 比較化合物として供試したAsp, DaaおよびDaによる活性とも類似の傾向を示し, ラクトン環をもつAspやDaで強い抑制作用を示すことより, イリドイド配糖体による植物生長抑制作用にラクトンが関与していることを確認した (Table 1, 2, 3)。

Normal mode analysis, with the all-atom or coarse-grained elastic network model, represents the equilibrium fluctuation of protein molecule in the Eckart frame, where contributions from external motions (translation and rotation) of the entire protein molecule are eliminated. On the other hand, domain motion is frequently exhibited by the relative motion of one domain to the other. Such a representation of fluctuations in the non-Eckart frame cannot be achieved by conventional normal mode analysis. Here, we propose normal mode analysis in a non-Eckart frame, where the external degrees of freedom are fixed for any portion of the system. In this analysis, the covariance matrix in the Eckart frame is transformed into one in the non-Eckart frame. Using a molecular dynamics simulation, we have confirmed the validity of the transformation formula and discussed the physical implication of the formula.

Background The changes in liver blood flow associated with living donor liver transplantation (LDLT) in children have not yet been studied. The aim of the present study was to investigate changes in hepatic hemodynamics before and after pediatric partial liver transplantation. Methods In 7 pediatric recipients with congenital cholestasis and native liver Child-Pugh classes B and C, portal vein flow (PVF) and hepatic arterial flow (HAF) were measured using an ultrasonic transit time flow meter before removal of the native liver and after transplantation and compared with donor left PVF and donor left HAF. Results The mean portal contribution to total hepatic blood flow was markedly decreased in the recipient native liver compared with that in the donor (69% ± 15% vs 32% ± 15%; P = .0003) and after reperfusion changed to almost the same ratio as that in the donor liver (73% ± 18%; P Conclusion The extreme imbalance between PVF and HAF that is common in implanted partial liver in adult LDLT recipients was not observed in pediatric LDLT. After transplantation of an appropriately sized liver graft, the portal contribution to total liver blood flow normalized to the value for normal liver.