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Sample records for similar fucosylated structures

  1. Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation.

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    Okuyama, Noriko; Ide, Yoshihito; Nakano, Miyako; Nakagawa, Tsutomu; Yamanaka, Kanako; Moriwaki, Kenta; Murata, Kohei; Ohigashi, Hiroaki; Yokoyama, Shigekazu; Eguchi, Hidetoshi; Ishikawa, Osamu; Ito, Toshifumi; Kato, Michio; Kasahara, Akinori; Kawano, Sunao; Gu, Jianguo; Taniguchi, Naoyuki; Miyoshi, Eiji

    2006-06-01

    Changes in oligosaccharide structures have been reported in certain types of malignant transformations and, thus, could be used for tumor markers in certain types of cancer. In the case of pancreatic cancer cell lines, a variety of fucosylated proteins are secreted into their conditioned media. To identify fucosylated proteins in the serum of patients with pancreatic cancer, we performed western blot analyses using Aleuria Aurantica Lectin (AAL), which is specific for fucosylated structures. An approximately 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the beta chain of haptoglobin. While the appearance of fucosylated haptoglobin has been reported in other diseases such as hepatocellular carcinoma, liver cirrhosis, gastric cancer and colon cancer, the incidence was significantly higher in the case of pancreatic cancer. Fucosylated haptoglobin was observed more frequently at the advanced stage of pancreatic cancer and disappeared after an operation. A mass spectrometry analysis of haptoglobin purified from the serum of patients with pancreatic cancer and the medium from a pancreatic cancer cell line, PSN-1, showed that the alpha 1-3/alpha 1-4/alpha 1-6 fucosylation of haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B, was cultured with the conditioned media from pancreatic cancer cells, haptoglobin secretion was dramatically increased. These findings suggest that fucosylated haptoglobin could serve as a novel marker for pancreatic cancer. Two possibilities were considered in terms of the fucosylation of haptoglobin. One is that pancreatic cancer cells, themselves, produce fucosylated haptoglobin; the other is that pancreatic cancer produces a factor, which induces the production of fucosylated haptoglobin in the liver.

  2. Fucosylated haptoglobin is a novel marker for pancreatic cancer: detailed analyses of oligosaccharide structures.

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    Miyoshi, Eiji; Nakano, Miyako

    2008-08-01

    Changes in oligosaccharide structures have been reported in certain types of malignant transformation and thus can be used as tumor markers in certain types of cancer. In the case of pancreatic cancer (PC) cell lines, a variety of fucosylated proteins are secreted into the conditioned media. To identify fucosylated proteins in the sera of patients with PC, we performed Western blot analysis using Aleuria Aurantia Lectin (AAL), which is specific for fucosylated structures. An approximately 40 kD protein was found to be highly fucosylated in PC and N-terminal analysis revealed that it was the beta chain of haptoglobin. While the appearance of fucosylated haptoglobin has been reported in other diseases such as hepatocellular carcinoma, liver cirrhosis, gastric cancer, and colorectal cancer, the incidence was significantly higher in the case of PC. Fucosylated haptoglobin was observed more frequently at the advanced stage of PC and disappeared after operation. Haptoglobin has four sites of N-glycans and site-directed oligosaccharide analysis involving MS was performed. Site-specific increases in fucosylation of bi-antennary glycans of sites 2 and 4, and of tri-antennary glycans of all sites were observed in PC, compared to in normal volunteers and chronic pancreatitis. Therefore, increases in fucosylation seem to be not due to inflammation, but cancer itself. Coculturing of a human hepatoma cell line, Hep3B, with PC cells-induced production of fucosylated haptoglobin, suggesting that PC produces a factor that induces the production of fucosylated haptoglobin. On clinical investigation of 100 cases of colorectal cancer, cases in which it was located near the liver showed a higher positive rate of fucosylated haptoglobin, suggesting that the location of the cancer might also be an important factor for fucosylated haptoglobin if cancer tissues produce such inducible factors. Thus, fucosylated haptoglobin could become a novel tumor marker for PC and complicated mechanisms

  3. Structural elucidation of fucosylated chondroitin sulfates from sea cucumber using FTICR-MS/MS.

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    Agyekum, Isaac; Pepi, Lauren; Yu, Yanlei; Li, Junhui; Yan, Lufeng; Linhardt, Robert J; Chen, Shiguo; Amster, I Jonathan

    2018-02-01

    Fucosylated chondroitin sulfates are complex polysaccharides extracted from sea cucumber. They have been extensively studied for their anticoagulant properties and have been implicated in other biological activities. While nuclear magnetic resonance spectroscopy has been used to extensively characterize fucosylated chondroitin sulfate oligomers, we herein report the first detailed mass characterization of fucosylated chondroitin sulfate using high-resolution Fourier transform ion cyclotron resonance mass spectrometry. The two species of fucosylated chondroitin sulfates considered for this work include Pearsonothuria graeffei (FCS-Pg) and Isostichopus badionotus (FCS-Ib). Fucosylated chondroitin sulfate oligosaccharides were prepared by N-deacetylation-deaminative cleavage of the two fucosylated chondroitin sulfates and purified by repeated gel filtration. Accurate mass measurements obtained from electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry measurements confirmed the oligomeric nature of these two fucosylated chondroitin sulfate oligosaccharides with each trisaccharide repeating unit averaging four sulfates per trisaccharide. Collision-induced dissociation of efficiently deprotonated molecular ions through Na/H + exchange proved useful in providing structurally relevant glycosidic and cross-ring product ions, capable of assigning the sulfate modifications on the fucosylated chondroitin sulfate oligomers. Careful examination of the tandem mass spectrometry of both species deferring in the positions of sulfate groups on the fucose residue (FCS-Pg-3,4- OS) and (FCS-Ib-2,4- OS) revealed cross-ring products 0,2 A αf and 2,4 X 2αf which were diagnostic for (FCS-Pg-3,4- OS) and 0,2 X 2αf diagnostic for (FCS-Ib-2,4- OS). Mass spectrometry and tandem mass spectrometry data acquired for both species varying in oligomer length (dp3-dp15) are presented.

  4. Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism.

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    Urbanowicz, Breeanna R; Bharadwaj, Vivek S; Alahuhta, Markus; Peña, Maria J; Lunin, Vladimir V; Bomble, Yannick J; Wang, Shuo; Yang, Jeong-Yeh; Tuomivaara, Sami T; Himmel, Michael E; Moremen, Kelley W; York, William S; Crowley, Michael F

    2017-09-01

    The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely because of the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase 1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable the sufficient production of the enzyme for X-ray crystallography, which reveals the structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. The lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  5. Fucosylation Is a Promising Target for Cancer Diagnosis and Therapy

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    Shinichiro Shinzaki

    2012-01-01

    Full Text Available Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. Recent advances in glycomics have identified several types of glyco-biomarkers containing fucosylation that are linked to certain types of cancer. Fucosylated alpha-fetoprotein (AFP is widely used in the diagnosis of hepatocellular carcinoma because it is more specific than alpha-fetoprotein. High levels of fucosylated haptoglobin have also been found in sera of patients with various carcinomas. We have recently established a simple lectin-antibody ELISA to measure fucosylated haptoglobin and to investigate its clinical use. Cellular fucosylation is dependent upon fucosyltransferase activity and the level of its donor substrate, guanosine diphosphate (GDP-fucose. GDP-mannose-4,6-dehydratase (GMDS is a key enzyme involved in the synthesis of GDP-fucose. Mutations of GMDS found in colon cancer cells induced a malignant phenotype, leading to rapid growth in athymic mice resistant to natural killer cells. This review describes the role of fucosylated haptoglobin as a cancer biomarker, and discusses the possible biological role of fucosylation in cancer development.

  6. Holothurian Fucosylated Chondroitin Sulfate

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    Vitor H. Pomin

    2014-01-01

    Full Text Available Fucosylated chondroitin sulfate (FucCS is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, FucCS has also sulfated fucosyl branching units 3-O-linked to the acid residues. The sulfation patterns of these branches vary accordingly with holothurian species and account for different biological actions and responses. FucCSs may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities, besides its beneficial effects in hemodialysis, cellular growth modulation, fibrosis and hyperglycemia. Through an historical overview, this document covers most of the science regarding the holothurian FucCS. Both structural and medical properties of this unique GAG, investigated during the last 25 years, are systematically discussed herein.

  7. Synthesis of the oligosaccharides related to branching sites of fucosylated chondroitin sulfates from sea cucumbers.

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    Ustyuzhanina, Nadezhda E; Fomitskaya, Polina A; Gerbst, Alexey G; Dmitrenok, Andrey S; Nifantiev, Nikolay E

    2015-02-02

    Natural anionic polysaccharides fucosylated chondroitin sulfates (FCS) from sea cucumbers attract great attention nowadays due to their ability to influence various biological processes, such as blood coagulation, thrombosis, angiogenesis, inflammation, bacterial and viral adhesion. To determine pharmacophore fragments in FCS we have started systematic synthesis of oligosaccharides with well-defined structure related to various fragments of these polysaccharides. In this communication, the synthesis of non-sulfated and selectively O-sulfated di- and trisaccharides structurally related to branching sites of FCS is described. The target compounds are built up of propyl β-d-glucuronic acid residue bearing at O-3 α-l-fucosyl or α-l-fucosyl-(1→3)-α-l-fucosyl substituents. O-Sulfation pattern in the fucose units of the synthetic targets was selected according to the known to date holothurian FCS structures. Stereospecific α-glycoside bond formation was achieved using 2-O-benzyl-3,4-di-O-chloroacetyl-α-l-fucosyl trichloroacetimidate as a donor. Stereochemical outcome of the glycosylation was explained by the remote participation of the chloroacetyl groups with the formation of the stabilized glycosyl cations, which could be attacked by the glycosyl acceptor only from the α-side. The experimental results were in good agreement with the SCF/MP2 calculated energies of such participation. The synthesized oligosaccharides are regarded as model compounds for the determination of a structure-activity relationship in FCS.

  8. Purification, structural characterization and anticoagulant properties of fucosylated chondroitin sulfate isolated from Holothuria mexicana.

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    Mou, Jiaojiao; Wang, Cong; Li, Wenjing; Yang, Jie

    2017-05-01

    A novel fucosylated chondroitin sulfate (HmG) was isolated from sea cucumber Holothuria mexicana, the structure of which was characterized by monosaccharide composition, disaccharide composition, IR, 1 H and 13 C NMR spectrum, additionally with two dimensional NMR spectrum of degraded HmG (DHmG). The backbone of HmG was identified as chondroitin 6-O sulfate, while the major O-4 sulfated fucose branches linked to O-3 position of glucuronic acid in almost every disaccharide unit. The anticoagulant activities of HmG and DHmG were assessed and compared with heparin and low molecular weight heparin. The results indicated that HmG and DHmG both could significantly prolong the activated partial thrombo-plastin time, and the properties were well related to its molecular weight. DHmG showed similar anticoagulant properties to low molecular weight heparin with less bleeding risks, making it a safer anticoagulant drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Structural characterization of fucosylated chondroitin sulfates from sea cucumbers Apostichopus japonicus and Actinopyga mauritiana.

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    Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Tsvetkova, Eugenia A; Shashkov, Alexander S; Stonik, Valentin A; Nifantiev, Nikolay E; Usov, Anatolii I

    2016-11-20

    Two samples of fucosylated chondroitin sulfate (FCS), AJ and AM, were isolated from holothurian species Apostichopus japonicus and Actinopyga mauritiana, respectively. Purification of FCS was performed by ion exchange chromatography followed by gel filtration. Structure of the biopolymers was elucidated using chemical and NMR spectroscopic methods. Both polysaccharides were shown to contain a typical chondroitin core built up of repeating disaccharide units →3)-β-d-GalNAc-(1→4)-β-d-GlcA-(1→ and decorated by sulfate groups and α-l-Fuc branches. Two polysaccharides were different in pattern of sulfation of GalNAc and fucosyl branches connected to O-3 of GlcA. The ratio of GalNAc4S6S:GalNAc4S for AJ was about 2:1, whereas for AM this value was approximately 1:1. AJ contained Fucp2S4S and Fucp3S4S residues linked to O-3 of GlcA in a ratio of 3:1, while for AM this ratio was 1:4. Small portions of Fucp4S units attached to O-3 of GlcA were also found in both polysaccharides. Moreover, in a structure of AM the presence of Fucp3S residues linked to O-6 of GalNAc were determined using the data of NMR spectra. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae: production of O-fucosylated epidermal growth factor domains.

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    Chigira, Yuko; Oka, Takuji; Okajima, Tetsuya; Jigami, Yoshifumi

    2008-04-01

    Development of a heterologous system for the production of homogeneous sugar structures has the potential to elucidate structure-function relationships of glycoproteins. In the current study, we used an artificial O-glycosylation pathway to produce an O-fucosylated epidermal growth factor (EGF) domain in Saccharomyces cerevisiae. The in vivo O-fucosylation system was constructed via expression of genes that encode protein O-fucosyltransferase 1 and the EGF domain, along with genes whose protein products convert cytoplasmic GDP-mannose to GDP-fucose. This system allowed identification of an endogenous ability of S. cerevisiae to transport GDP-fucose. Moreover, expression of EGF domain mutants in this system revealed the different contribution of three disulfide bonds to in vivo O-fucosylation. In addition, lectin blotting revealed differences in the ability of fucose-specific lectin to bind the O-fucosylated structure of EGF domains from human factors VII and IX. Further introduction of the human fringe gene into yeast equipped with the in vivo O-fucosylation system facilitated the addition of N-acetylglucosamine to the EGF domain from factor IX but not from factor VII. The results suggest that engineering of an O-fucosylation system in yeast provides a powerful tool for producing proteins with homogenous carbohydrate chains. Such proteins can be used for the analysis of substrate specificity and the production of antibodies that recognize O-glycosylated EGF domains.

  11. Generation of a Mutant Mucor hiemalis Endoglycosidase That Acts on Core-fucosylated N-Glycans.

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    Katoh, Toshihiko; Katayama, Takane; Tomabechi, Yusuke; Nishikawa, Yoshihide; Kumada, Jyunichi; Matsuzaki, Yuji; Yamamoto, Kenji

    2016-10-28

    Endo-β-N-acetylglucosaminidase M (Endo-M), an endoglycosidase from the fungus Mucor hiemalis, is a useful tool for chemoenzymatic synthesis of glycoconjugates, including glycoprotein-based therapeutics having a precisely defined glycoform, by virtue of its transglycosylation activity. Although Endo-M has been known to act on various N-glycans, it does not act on core-fucosylated N-glycans, which exist widely in mammalian glycoproteins, thus limiting its application. Therefore, we performed site-directed mutagenesis on Endo-M to isolate mutant enzymes that are able to act on mammalian-type core-α1,6-fucosylated glycans. Among the Endo-M mutant enzymes generated, those in which the tryptophan at position 251 was substituted with alanine or asparagine showed altered substrate specificities. Such mutant enzymes exhibited increased hydrolysis of a synthetic α1,6-fucosylated trimannosyl core structure, whereas their activity on the afucosylated form decreased. In addition, among the Trp-251 mutants, the W251N mutant was most efficient in hydrolyzing the core-fucosylated substrate. W251N mutants could act on the immunoglobulin G-derived core-fucosylated glycopeptides and human lactoferrin glycoproteins. This mutant was also capable of transferring the sialyl glycan from an activated substrate intermediate (sialyl glyco-oxazoline) onto an α1,6-fucosyl-N-acetylglucosaminyl biotin. Furthermore, the W251N mutant gained a glycosynthase-like activity when a N175Q substitution was introduced and it caused accumulation of the transglycosylation products. These findings not only give insights into the substrate recognition mechanism of glycoside hydrolase family 85 enzymes but also widen their scope of application in preparing homogeneous glycoforms of core-fucosylated glycoproteins for the production of potent glycoprotein-based therapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma.

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    Mary Ann Comunale

    2010-08-01

    Full Text Available We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT. To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC.Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (alpha-1,3 fucosylation. Increases in core (alpha-1,6 fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL, specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific.This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification.

  13. Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

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    Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

    2018-06-01

    Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. Modulation of GDP-fucose level for generating proteins with reduced rate of fucosylation (WO2010141855).

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    Taupin, Philippe

    2011-09-01

    The application (WO2010141855) is in the field of glycobiology, and involves the control of the rate of fucosylation of proteins by exogenous factors. It aims at controlling the rate of protein fucosylation with inhibitors (drugs or nucleic acid antagonists) of enzymes involved in the synthesis of GDP-fucose. Mammalian cell lines were cultured in the presence of inhibitors, for example, siRNA. The rates of GDP-fucose in cells and during protein fucosylation were characterized. The level of protein fucosylation decreases rapidly in response to a decrease in GDP-fucose level. The relationship between the rate of fucosylation of proteins and the level of GDP-fucose in a cell is non-linear. Reduction in the rate of protein fucosylation can be achieved with a minimal reduction of the level of GDP-fucose in cells. The paradigm may be used to synthesize proteins and antibodies, with a reduced rate of fucosylation. The application claims that the use of drugs or nucleic acid antagonists that inhibit the enzymes involved in GDP-fucose biosynthesis optimizes the level of GDP-fucose present in cells, and reduces the rate of fucosylation of glycoproteins.

  15. Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM.

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    Ma, Junfeng; Sanda, Miloslav; Wei, Renhuizi; Zhang, Lihua; Goldman, Radoslav

    2018-02-07

    Aberrant core fucosylation of proteins has been linked to liver diseases. In this study, we carried out multiple reaction monitoring (MRM) quantification of core fucosylated N-glycopeptides of serum proteins partially deglycosylated by a combination of endoglycosidases (endoF1, endoF2, and endoF3). To minimize variability associated with the preparatory steps, the analysis was performed without enrichment of glycopeptides or fractionation of serum besides the nanoRP chromatography. Specifically, we quantified core fucosylation of 22 N-glycopeptides derived from 17 proteins together with protein abundance of these glycoproteins in a cohort of 45 participants (15 disease-free control, 15 fibrosis and 15 cirrhosis patients) using a multiplex nanoUPLC-MS-MRM workflow. We find increased core fucosylation of 5 glycopeptides at the stage of liver fibrosis (i.e., N630 of serotransferrin, N107 of alpha-1-antitrypsin, N253 of plasma protease C1 inhibitor, N397 of ceruloplasmin, and N86 of vitronectin), increase of additional 6 glycopeptides at the stage of cirrhosis (i.e., N138 and N762 of ceruloplasmin, N354 of clusterin, N187 of hemopexin, N71 of immunoglobulin J chain, and N127 of lumican), while the degree of core fucosylation of 10 glycopeptides did not change. Interestingly, although we observe an increase in the core fucosylation at N86 of vitronectin in liver fibrosis, core fucosylation decreases on the N169 glycopeptide of the same protein. Our results demonstrate that the changes in core fucosylation are protein and site specific during the progression of fibrotic liver disease and independent of the changes in the quantity of N-glycoproteins. It is expected that the fully optimized multiplex LC-MS-MRM assay of core fucosylated glycopeptides will be useful for the serologic assessment of the fibrosis of liver. We have quantified the difference in core fucosylation among three comparison groups (healthy control, fibrosis and cirrhosis patients) using a sensitive and

  16. Glycoprotein fucosylation is increased in seminal plasma of subfertile men

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    Beata Olejnik

    2015-04-01

    Full Text Available Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitroby fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin (AAL. Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, α1 -acid glycoprotein, α1 -antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade.

  17. Presence of fucosyl residues on the oligosaccharide antennae of membrane glycopeptides of human neuroblastoma cells

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    Santer, U.V.; Glick, M.C.

    1983-01-01

    Fucosyl residues linked alpha 1 leads to 3 or 4 to N-acetylglucosamine were found in large amounts on glycopeptides from the membranes of human tumor cells of neurectodermal origin but not on membrane glycopeptides from human fibroblasts. The fucosyl residues were detected by release of radioactive fucose from the glycopeptides with an almond alpha-L-fucosidase specific for fucosyl alpha 1 leads to 3(4)-N-acetylglucosamine. In other studies, the linkage was shown to be alpha 1 leads to 3 by nuclear magnetic resonance analysis. Glycopeptides containing these fucosyl residues from four human neuroblastoma cell lines were defined by binding to immobilized lectins. In addition, the glycopeptides from one human neuroblastoma cell line, CHP-134, were further characterized by enzyme degradation and columns calibrated for size and charge. The antennary position of fucosyl alpha 1 leads to 3-N-acetylglucosamine on the glycopeptides was demonstrated by the use of exoglycosidases and endoglycosidase D, since complete degradation to yield fucosyl-N-acetylglucosaminylasparagine was obtained only after treatment with almond alpha-L-fucosidase prior to the sequential degradation. Fucosyl alpha 1 leads to 3-N-acetylglucosamine was present on most size and charge classes of membrane glycopeptides and therefore was not limited to a few glycoproteins. Since the almond alpha-L-fucosidase cleaves fucosyl residues from glycoproteins, the physiological effects of the increased specific fucosylation on human tumors of neurectodermal origin can be examined

  18. Medical Gains of Chondroitin Sulfate Upon Fucosylation.

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    Pomin, Vitor H

    2015-01-01

    Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) composed of alternating N-acetyl galactosamine and glucuronic acid units within disaccharide building blocks. CS is a key functional component in proteoglycans of cartilaginous tissues. Owing to its numerous biological roles, CS is widely explored in the pharmaceutical market as nutraceutical ingredient commonly utilized against arthritis, osteoarthrosis, and sometimes osteoporosis. Tissues like shark cartilage and bovine trachea are common sources of CS. Nonetheless, a new CS type has been introduced and investigated in the last few decades in what regards its medical potentials. It is named fucosylated chondroitin sulfate (FucCS). This less common CS type is isolated exclusively from the body wall of sea cucumbers. The presence of fucosyl branching units in the holothurian FucCS gives to this unique GAG, therapeutic properties in various pathophysiological systems which are inexistent in the common CS explored in the market. Examples of these systems are coagulation, thrombosis, hemodialysis, atherosclerosis, cellular growth, angiogenesis, fibrosis, tumor growth, inflammation, viral and protozoan infections, hyperglycemia, diabetes-related pathological events and tissue damage. This report aims at describing the medical benefits gained upon fucosylation of CS. Clinical prospects of these medical benefits are also discussed herein.

  19. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

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    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J H M; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C Ellen; Vidarsson, Gestur

    2015-03-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with FcγRIII, with less Fc-fucosylation strengthening the interaction. Anti-D IgG1 Fc-glycosylation patterns in 93 plasma samples from 28 male and 28 female Dutch HIDs and RhIG were analyzed with mass spectrometry. The Fc-glycosylation profiles of HIDs were evaluated with regard to their immunization history. HID sera demonstrated clearly lowered anti-D Fc-fucosylation compared to normal IgG fucosylation (93%); this was more pronounced for female than for male HIDs (47% vs. 65%, p = 0.001). RhIG preparations from seven manufacturers varied greatly in the level of Fc-fucosylation (56%-91%). The level of fucosylation slightly increased upon repeated immunization, although it remained fairly constant over time. The RhIG from the different manufacturers all demonstrated increased Fc-galactosylation (64%-82%) compared to total IgG (38%-51%). RhIG preparations vary in Fc-fucosylation and all demonstrate increased galactosylation. Despite not knowing the exact working mechanism, immunoprophylaxis could perhaps be optimized by selection of donors whose anti-D have low amounts of Fc-fucose, to increase the clearance activity of anti-D preparations, as well as high amounts of galactosylation, for anti-inflammatory effects. Implementing a biologic assay in the standardization of RhIG preparations might be considered. © 2014 AABB.

  20. Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions.

    Directory of Open Access Journals (Sweden)

    John Bienenstock

    Full Text Available Human milk oligosaccharides (HMO are being studied by different groups exploring a broad range of potential beneficial effects to the breastfed infant. Many of these effects have been attributed to a growth promotion effect on certain gut organisms such as bifidobacteria. Additionally, evidence indicates that HMO are able to directly promote positive changes in gut epithelium and immune responses under certain conditions. This study utilizes a standardized ex vivo murine colon preparation to examine the effects of sialylated, fucosylated and other HMO on gut motor contractions. Only the fucosylated molecules, 2'FL and 3'FL, decreased contractility in a concentration dependent fashion. On the basis of IC50 determinations 3'FL was greater than 2 times more effective than 2'FL. The HMO 3'SL and 6'SL, lacto-N-neotetraose (LNnT, and galactooligosaccharides (GOS elicited no effects. Lactose was used as a negative control. Fucosylation seems to underlie this functional regulation of gut contractility by oligosaccharides, and L-fucose, while it was also capable of reducing contractility, was substantially less effective than 3'FL and 2'FL. These results suggest that specific HMO are unlikely to be having these effects via bifidogenesis, but though direct action on neuronally dependent gut migrating motor complexes is likely and fucosylation is important in providing this function, we cannot conclusively shown that this is not indirectly mediated. Furthermore they support the possibility that fucosylated sugars and fucose might be useful as therapeutic or preventative adjuncts in disorders of gut motility, and possibly also have beneficial central nervous system effects.

  1. Structure and biological activity of a fucosylated chondroitin sulfate from the sea cucumber Cucumaria japonica.

    Science.gov (United States)

    Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Shashkov, Alexander S; Kusaykin, Mikhail I; Stonik, Valentin A; Nifantiev, Nikolay E; Usov, Anatolii I

    2016-05-01

    A fucosylated chondroitin sulfate (FCS) was isolated from the body wall of Pacific sea cucumber Cucumaria japonicaby extraction in the presence of papain followed by Cetavlon precipitation and anion-exchange chromatography. FCS was shown to contain D-GalNAc, D-GlcA, L-Fuc and sulfate in molar proportions of about 1:1:1:4.5. Structure of FCS was elucidated using NMR spectroscopy and methylation analysis of the native polysaccharide and products of its desulfation and carboxyl reduction. The polysaccharide was shown to contain a typical chondroitin core → 3)-β-D-GalNAc-(1 → 4)-β-D-GlcA-(1 →. Sulfate groups in this core occupy O-4 and the majority of O-6 of GalNAc. Fucosyl branches are represented by 3,4- and 2,4-disulfated units in a ratio of 4:1 and are linked to O-3 of GlcA. In addition, ∼ 33% of GlcA are 3-O-sulfated, and hence, the presence of short fucooligosaccharide chains side by side with monofucosyl branches cannot be excluded. FCS was shown to inhibit platelets aggregation in vitro mediated by collagen and ristocetin, but not adenosine diphosphate, and demonstrated significant anticoagulant activity, which is connected with its ability to enhance inhibition of thrombin and factor Xa by antithrombin III, as well as to influence von Willebrand factor activity. The latest property significantly distinguished FCS from low-molecular-weight heparin. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma

    Science.gov (United States)

    Wang, Yiwei; Huang, Dan; Chen, Kai-Yuan; Cui, Min; Wang, Weihuan; Huang, Xiaoran; Awadellah, Amad; Li, Qing; Friedman, Ann; Xin, William W.; Di Martino, Luca; Cominelli, Fabio; Miron, Alex; Chan, Ricky; Fox, James; Xu, Yan; Shen, Xiling; Kalady, Mathew F.; Markowitz, Sanford; Maillard, Ivan; Lowe, John B.; Xin, Wei; Zhou, Lan

    2016-01-01

    Background & Aims De novo synthesis of GDP-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or TSTA3). GMDS deletions and mutations are found in 6%–13% of colorectal cancers; these mostly affect ascending and transverse colon. We investigated whether lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. Methods FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx–/– mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by ELISAs to measure cytokine levels; T cells were also collected and analyzed. Fecal samples were analyzed by 16s rRNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx–/– or control mice (Ly5.2) into irradiated 8-week old Fx–/– or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided). Results Fx–/– mice developed colitis and serrated-like lesions. The intestinal pathology of Fx–/– mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx–/– mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency altered the composition of the fecal microbiota, reduced

  3. Two fucosylated chondroitin sulfates from the sea cucumber Eupentacta fraudatrix.

    Science.gov (United States)

    Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Nifantiev, Nikolay E; Usov, Anatolii I

    2017-05-15

    Two fucosylated chondroitin sulfates EF1 and EF2 were isolated from the sea cucumber Eupentacta fraudatrix. Separation of the polysaccharides was performed using anion-exchange chromatography on DEAE-Sephacel by elution of 0.75M and 1.0M NaCl solutions. The structures of biopolymers were determined by chemical and NMR spectroscopic methods. The backbone of EF1 was found to be composed of chondroitin sulfate A and E units in a ratio of about 1:1. The core of EF2 along with chondroitin sulfate A and E fragments contained unusual disaccharide repeating units →4)-β-d-GlcpA2S3S-(1→3)-β-d-GalpNAc6S-(1→. The main type of branches in both polysaccharides was α-l-Fucp3S4S unit attached to O-3 of GlcA residues. Another type of branches was found to be the disaccharide fragment α-l-Fucp-(1→2)-α-l-Fucp3S4S-(1→ linked to O-3 of GlcA. The presence of structurally different fucosylated chondroitin sulfates in one species of sea cucumber is rather unusual and has not been described previously. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Synthesis and NMR analysis of model compounds related to fucosylated chondroitin sulfates: GalNAc and Fuc(1 → 6)GalNAc derivatives.

    Science.gov (United States)

    Vinnitskiy, Dmitry Z; Ustyuzhanina, Nadezhda E; Dmitrenok, Andrey S; Shashkov, Alexander S; Nifantiev, Nikolay E

    2017-01-13

    Unsubstituted and 6-O-α-L-fucosylated propyl 2-acetamido-2-deoxy-β-D-galactopyranosides and their selectively O-sulfated (both in GalNAc and Fuc units) derivatives were synthesized as model compounds representing the fragments of fucosylated chondroitin sulfates (FCS) from sea cucumbers. Per-O-acetylated 2-deoxy-2-N-phthalimido-D-glucopyranose was used as a key precursor for the preparation of all 2-acetamido-2-deoxy-D-galactopyranoside containing products. Attempts at 6-O-glycosylation of propyl 3-O-benzoyl-2-deoxy-2-N-phthalimido-D-galactoside by 2-O-benzyl-3,4-di-O-chloracetyl-L-fucosyl trichloracetimidate in the presence of TMSOTf gave a 1:1 mixture of the corresponding α- and β-isomeric disaccharides, while the use of structurally related fucosyl bromide donor with promotion by Bu 4 NBr led to the formation of desired α-isomeric disaccharide exclusively. Selective removal of orthogonal O-protections permitted subsequent O-sulfation both at the GalNAc and Fuc units. Further removal of blocking groups yielded the target products which were systematically studied by 1 H and 13 C NMR spectroscopy in order to determine the spectral effects of O-sulfation and α-L-fucosylation needed for the development of computer assisted structural analysis of natural FCS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Antithrombotic activities of fucosylated chondroitin sulfates and their depolymerized fragments from two sea cucumbers.

    Science.gov (United States)

    Liu, Xiaoxiao; Hao, Jiejie; Shan, Xindi; Zhang, Xiao; Zhao, Xiaoliang; Li, Qinying; Wang, Xiaojiang; Cai, Chao; Li, Guoyun; Yu, Guangli

    2016-11-05

    Fucosylated chondroitin sulfate (FCS), a glycosaminoglycan extracted from the body wall of sea cucumber, is a promising antithrombotic agent. The chemical structures of FCSc isolated from sea cucumber Cucumaria frondosa and its depolymerized fragment (dFCSc) were characterized for the first time. Additionally, anticoagulant and antithrombotic activities were evaluated in vitro and in vivo. The results demonstrated that dFCSc exhibited better antithrombotic-hemorrhagic ratio than native FCSc on the electrical induced arterial thrombosis model in rats. Compared to FCSt obtained from Thelenota ananas, FCSc possessed different sulfation patterns but similar antithrombotic effects. Therefore, sulfation pattern of FCS might not affect anticoagulation and antithrombosis as much as molecular weight may. Our results proposed a new point of view to understand the structure-activity relationship of FCS as alternative agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma.

    Science.gov (United States)

    Wang, Yiwei; Huang, Dan; Chen, Kai-Yuan; Cui, Min; Wang, Weihuan; Huang, Xiaoran; Awadellah, Amad; Li, Qing; Friedman, Ann; Xin, William W; Di Martino, Luca; Cominelli, Fabio; Miron, Alex; Chan, Ricky; Fox, James G; Xu, Yan; Shen, Xiling; Kalady, Mathew F; Markowitz, Sanford; Maillard, Ivan; Lowe, John B; Xin, Wei; Zhou, Lan

    2017-01-01

    De novo synthesis of guanosine diphosphate (GDP)-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or tissue specific transplantation antigen P35B [TSTA3]). GMDS deletions and mutations are found in 6%-13% of colorectal cancers; these mostly affect the ascending and transverse colon. We investigated whether a lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx-/- mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by enzyme-linked immunosorbent assays to measure cytokine levels; T cells also were collected and analyzed. Fecal samples were analyzed by 16s ribosomal RNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx-/- or control mice (Ly5.2) into irradiated 8-week-old Fx-/- or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided). Fx-/- mice developed colitis and serrated-like lesions. The intestinal pathology of Fx-/- mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx-/- mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency

  7. FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.

    Science.gov (United States)

    Louie, Salina; Haley, Benjamin; Marshall, Brett; Heidersbach, Amy; Yim, Mandy; Brozynski, Martina; Tang, Danming; Lam, Cynthia; Petryniak, Bronislawa; Shaw, David; Shim, Jeongsup; Miller, Aaron; Lowe, John B; Snedecor, Brad; Misaghi, Shahram

    2017-03-01

    During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells. ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s). Several strategies have been utilized to generate fully afucosylated antibodies. A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans. However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo. Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation. Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media. Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities. Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody. Biotechnol. Bioeng. 2017;114: 632-644. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase.

    Science.gov (United States)

    Wu, Mingyi; Wen, Dandan; Gao, Na; Xiao, Chuang; Yang, Lian; Xu, Li; Lian, Wu; Peng, Wenlie; Jiang, Jianmin; Zhao, Jinhua

    2015-03-06

    Fucosylated chondroitin sulfate (FCS), a structurally unusual glycosaminoglycan, has distinct anticoagulant properties, and is an especially strong inhibitor of the intrinsic factor Xase (anti-Xase). To obtain a highly selective inhibitor of human Xase, we purified six native FCSs with various sulfation patterns, prepared a series of FCS derivatives, and then elucidated the relationship between the structures and the anticoagulant activities of FCSs. FCSs 1-3 containing higher Fuc2S4S exhibit stronger AT-dependent anti-IIa activities, whereas 4-6 containing more Fuc3S4S produce potent HCII-dependent anti-IIa activities. Saccharides containing a minimum of 6-8 trisaccharide units, free carboxyl groups, and full fucosylation of GlcA may be required for potent anti-Xase activity, and approximately six trisaccharide units and partial fucosylation of GlcA may contribute to potent HCII-dependent activity. Decreasing of the molecular weights markedly reduces their AT-dependent anti-IIa activities, and even eliminates human platelet and factor XII activation. Furthermore, in vitro and in vivo studies suggested that fractions of 6-12 kDa may be very promising compounds as putative selective intrinsic Xase inhibitors with antithrombotic action, but without the consequences of major bleeding and factor XII activation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells

    Science.gov (United States)

    Zheng, Li; Matossian, Margarite; Prince, Mark E.; Paino, Francesca; Mele, Luigi; Papaccio, Federica; Montella, Roberta; Papaccio, Gianpaolo; Papagerakis, Silvana

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with high mortality rates. Major challenges for OSCC management include development of resistance to therapy and early formation of distant metastases. Cancer stem cells (CSCs) have emerged as important players in both pathologic mechanisms. Increased fucosylation activity and increased expression of fucosylated polysaccharides, such as Sialyl Lewis X (SLex), are associated with invasion and metastasis. However, the role of fucosylation in CSCs has not been elucidated yet. We used the spheroid culture technique to obtain a CSC-enriched population and compared orospheres with adherent cells. We found that orospheres expressed markers of CSCs and metastasis at higher levels, were more invasive and tumorigenic, and were more resistant to cisplatin/radiation than adherent counterparts. We found fucosyltransferases FUT3 and FUT6 highly up-regulated, increased SLex expression and increased adhesion by shear flow assays in orospheres. Inhibition of fucosylation negatively affected orospheres formation and invasion of oral CSCs. These results confirm that orospheres are enriched in CSCs and that fucosylation is of paramount importance for CSC invasion. In addition, SLex may play a key role in CSC metastasis. Thus, inhibition of fucosylation may be used to block CSCs and metastatic spread. PMID:25428916

  10. Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

    Science.gov (United States)

    Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

    2018-02-01

    Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Structural Elucidation and Biological Activity of a Highly Regular Fucosylated Glycosaminoglycan from the Edible Sea Cucumber Stichopus herrmanni.

    Science.gov (United States)

    Li, Xiaomei; Luo, Lan; Cai, Ying; Yang, Wenjiao; Lin, Lisha; Li, Zi; Gao, Na; Purcell, Steven W; Wu, Mingyi; Zhao, Jinhua

    2017-10-25

    Edible sea cucumbers are widely used as a health food and medicine. A fucosylated glycosaminoglycan (FG) was purified from the high-value sea cucumber Stichopus herrmanni. Its physicochemical properties and structure were analyzed and characterized by chemical and instrumental methods. Chemical analysis indicated that this FG with a molecular weight of ∼64 kDa is composed of N-acetyl-d-galactosamine, d-glucuronic acid (GlcA), and l-fucose. Structural analysis clarified that the FG contains the chondroitin sulfate E-like backbone, with mostly 2,4-di-O-sulfated (85%) and some 3,4-di-O-sulfated (10%) and 4-O-sulfated (5%) fucose side chains that link to the C3 position of GlcA. This FG is structurally highly regular and homogeneous, differing from the FGs of other sea cucumbers, for its sulfation patterns are simpler. Biological activity assays indicated that it is a strong anticoagulant, inhibiting thrombin and intrinsic factor Xase. Our results expand the knowledge on structural types of FG and illustrate its biological activity as a functional food material.

  12. Fucosylated glycans in the periventricular structures and the cerebrospinal fluid of the fetal rat forebrain. An autoradiographic and lectin binding histiotopic study

    Czech Academy of Sciences Publication Activity Database

    Mareš, Vladislav; Brückner, G.

    2001-01-01

    Roč. 19, č. 3 (2001), s. 297-303 ISSN 0736-5748 Institutional research plan: CEZ:AV0Z5011922 Keywords : fetal rat brain * fucosylated glycans * cerebrospinal fluid Subject RIV: FH - Neurology Impact factor: 2.156, year: 2001

  13. Identification of α(1,6)fucosylated proteins differentially expressed in human colorectal cancer

    International Nuclear Information System (INIS)

    Muinelo-Romay, Laura; Villar-Portela, Susana; Cuevas, Elisa; Gil-Martín, Emilio; Fernández-Briera, Almudena

    2011-01-01

    A universal hallmark of cancer cells is the change in their glycosylation phenotype. One of the most frequent alterations in the normal glycosylation pattern observed during carcinogenesis is the enhancement of α(1,6)linked fucose residues of glycoproteins, due to the up-regulation of the α(1,6)fucosyltransferase activity. Our previous results demonstrated the specific alteration of this enzyme activity and expression in colorectal cancer, suggesting its implication in tumour development and progression. In the current work we combined a LCA-affinity chromatography with SDS-PAGE and mass spectrometry in order to identify α(1,6)fucosylated proteins differentially expressed in colorectal cancer. This strategy allowed the identification of a group of α(1,6)fucosylated proteins candidates to be involved in CRC malignancy. The majority of the identified proteins take part in cell signaling and interaction processes as well as in modulation of the immunological response. Likewise, we confirmed the increased expression of GRP94 in colorectal cancer tissue and the significant down-regulation of the IgGFcBP expression in tumour cells. All these results validate the importance of core-fucosylated proteins profile analysis to understand the mechanisms which promote cancer onset and progression and to discover new tumour markers or therapeutic targets

  14. Exploring the structure of fucosylated chondroitin sulfate through bottom-up nuclear magnetic resonance and electrospray ionization-high-resolution mass spectrometry approaches.

    Science.gov (United States)

    Santos, Gustavo Rc; Porto, Ana Co; Soares, Paulo Ag; Vilanova, Eduardo; Mourão, Paulo As

    2017-07-01

    Fucosylated chondroitin sulfate (FCS) from sea cucumbers is composed of a chondroitin sulfate (CS) central core and branches of sulfated fucose. The structure of this complex glycosaminoglycan is usually investigated via nuclear magnetic resonance (NMR) analyses of the intact molecule, ergo through a top-down approach, which often yield spectra with intricate sets of signals. Here we employed a bottom-up approach to analyze the FCSs from the sea cucumbers Isostichopus badionotus and Ludwigothurea grisea from their basic constituents, viz. CS cores and sulfated fucose branches, obtained via systematic fragmentation through mild acid hydrolysis. Oligosaccharides derived from the central CS core were analyzed via NMR spectroscopy and the disaccharides produced using chondroitin sulfate lyase via SAX-HPLC. The CS cores from the two species were similar, showing only slight differences in the proportions of 4- or 6-monosulfated and 4,6-disulfated β-d-GalNAc. Sulfated fucose units released from the FCSs were analyzed via NMR and ESI-HRMS spectroscopies. The fucose units from each species presented extensive qualitative differences, but quantitative assessments of these units were hindered, mostly because of their extensive desulfation during the hydrolysis. The bottom-up analysis performed here has proved useful to explore the structure of FCS through a sum-of-the-parts approach in a qualitative manner. We further demonstrate that under specific acidification conditions particular fucose branches can be removed preferentially from FCS. Preparation of derivatives enriched with particular fucose branches could be useful for studies on "structure vs. biological function" of FCS. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. An endoglycosidase-assisted LC-MS/MS-based strategy for the analysis of site-specific core-fucosylation of low-concentrated glycoproteins in human serum using prostate-specific antigen (PSA) as example.

    Science.gov (United States)

    Lang, Robert; Leinenbach, Andreas; Karl, Johann; Swiatek-de Lange, Magdalena; Kobold, Uwe; Vogeser, Michael

    2018-05-01

    Recently, site-specific fucosylation of glycoproteins has attracted attention as it can be associated with several types of cancers including prostate cancer. However, individual glycoproteins, which might serve as potential cancer markers, often are very low-concentrated in complex serum matrices and distinct glycan structures are hard to detect by immunoassays. Here, we present a mass spectrometry-based strategy for the simultaneous analysis of core-fucosylated and total prostate-specific antigen (PSA) in human serum in the low ng/ml concentration range. Sample preparation comprised an immunoaffinity capture step to enrich total PSA from human serum using anti-PSA antibody coated magnetic beads followed by consecutive two-step on-bead partial deglycosylation with endoglycosidase F3 and tryptic digestion prior to LC-MS/MS analysis. The method was shown to be linear from 0.5 to 60 ng/ml total PSA concentrations and allows the simultaneous quantification of core-fucosylated PSA down to 1 ng/ml and total PSA lower than 0.5 ng/ml. The imprecision of the method over two days ranged from 9.7-23.2% for core-fucosylated PSA and 10.3-18.3% for total PSA depending on the PSA level. The feasibility of the method in native sera was shown using three human specimens. To our knowledge, this is the first MS-based method for quantification of core-fucosylated PSA in the low ng/ml concentration range in human serum. This method could be used in large patient cohorts as core-fucosylated PSA may be a diagnostic biomarker for the differentiation of prostate cancer and other prostatic diseases, such as benign prostatic hyperplasia (BPH). Furthermore, the described strategy could be used to monitor potential changes in site-specific core-fucosylation of other low-concentrated glycoproteins, which could serve as more specific markers ("marker refinement") in cancer research. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

    Science.gov (United States)

    Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

    2010-05-01

    We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

  17. Variations of pH as an additional tool in the analysis of crowded NMR spectra of fucosylated chondroitin sulfates.

    Science.gov (United States)

    Ustyuzhanina, Nadezhda E; Dmitrenok, Andrey S; Bilan, Maria I; Shashkov, Alexander S; Gerbst, Alexey G; Usov, Anatolii I; Nifantiev, Nikolay E

    2016-03-24

    The influence of pH variation on chemical shift values in NMR spectra of fucosylated chondroitin sulfates was studied using polysaccharides isolated from three sea cucumber species Apostichopus japonicus, Actinopyga mauritiana and Cucumaria japonica. The signals of glucuronic acid residues were found to be the most sensitive to pH changes in comparison to the chemical shifts of the sulfated galactosamine and fucosyl units, most of which were altered insignificantly. It was shown that in the presence of imidazole-HCl buffer (pH 7.2) NMR spectra of the polysaccharides from A. japonicus and A. mauritiana were sufficiently resolved, whereas under acidic conditions their (1)H NMR spectra were complicated by overlapping of H-1 signals of GlcA and GalNAc. In the case of polysaccharide from C. japonica bearing 3-O-fucosylated and 3-O-sulfated glucuronic acid residues in the backbone, acidification of the medium led to separation of H-1 signals of GlcA3S and GalNAc. Therefore, the combination of data obtained at different pH values may be useful for interpretation of overcrowded spectra of fucosylated chondroitin sulfates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Xyloglucans of Monocotyledons Have Diverse Structures

    Institute of Scientific and Technical Information of China (English)

    Yves S.Y. Hsieh; Philip J. Harris

    2009-01-01

    Except in the Poaceae, little is known about the structures of the xyloglucans in the primary walls of mono-cotyledons. Xyloglucan structures in a range of monocotyledon species were examined. Wall preparations were isolated, extracted with 6 M sodium hydroxide, and the extracts treated with a xyloglucan-specific endo-(1→4)-β-glucanase prep-aration. The oligosaccharides released were analyzed by high-performance anion-exchange chromatography and by ma-trix-assisted laser-desorption ionization time-of-flight mass spectrometry. Oligosaccharide profiles of the non-commelinid monocotyledons were similar to those of most eudicotyledons, indicating the xyloglucans were fucogalactoxyloglucans, with a XXXG ~a core motif and the fucosylated units XXFG and XLFG. An exception was Lemna minor (Araceae), which yielded no fucosylated oligosaccharides and had both XXXG and XXG_n core motifs. Except for the Arecales (palms) and the Dasypogonaceae, which had fucogalactoxyloglucans, the xyloglucans of the commelinid monocotyledons were structurally different. The Zingiberales and Commelinales had xyloglucans with both XXG_n and XXXG core motifs; small proportions of XXFG units, but no XLFG units, were present. In the Poales, the Poaceae had xyloglucans with a XXG_n core motif and no fucosylated units. In the other Poales families, some had both XXXG and XXG_n core motifs, others had only XXXG; XXFG units were present, but XLFG units were not.

  19. Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

    Science.gov (United States)

    Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

    2006-01-01

    Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

  20. Stage-specific synthesis and fucosylation of plasma membrane proteins by mouse pachytene spermatocytes and round spermatids in culture

    International Nuclear Information System (INIS)

    Gerton, G.L.; Millette, C.F.

    1986-01-01

    Little is known about the ability of mammalian spermatogenic cells to synthesize plasma membrane components in the presence or absence of Sertoli cells. In this study, purified populations (greater than 90%) of pachytene spermatocytes or round spermatids were isolated by unit gravity sedimentation and cultured for 20-24 h in the presence of [ 35 S]methionine or [ 3 H] fucose. Cell viabilities remained over 90% during the course of these experiments. Plasma membranes were purified from these cells and analyzed by two-dimensional gel electrophoresis. Qualitatively, the same plasma membrane proteins were synthesized by both cell types with the exception of the major Concanavalin A-binding glycoprotein, p151; the synthesis of p151 is greatly diminished or inhibited after meiosis. [3H]Fucose was incorporated into at least 6 common glycoproteins of both cells. Eight components fucosylated with molecular weights from 35,000 to 120,000 were specific to pachytene spermatocyte membranes. One fast-migrating fucosylated component may represent an uncharacterized lipid whose synthesis is terminated after meiosis. Round spermatids specifically fucosylated two components with molecular weights of 45,000 and 80,000. These results demonstrate the viability of germ cells of the male mouse in short-term culture and show that they are capable of synthesizing and fucosylating plasma membrane components in the absence of Sertoli cells

  1. O-fucosylation of the notch ligand mDLL1 by POFUT1 is dispensable for ligand function.

    Directory of Open Access Journals (Sweden)

    Julia Müller

    Full Text Available Fucosylation of Epidermal Growth Factor-like (EGF repeats by protein O-fucosyltransferase 1 (POFUT1 in vertebrates, OFUT1 in Drosophila is pivotal for NOTCH function. In Drosophila OFUT1 also acts as chaperone for Notch independent from its enzymatic activity. NOTCH ligands are also substrates for POFUT1, but in Drosophila OFUT1 is not essential for ligand function. In vertebrates the significance of POFUT1 for ligand function and subcellular localization is unclear. Here, we analyze the importance of O-fucosylation and POFUT1 for the mouse NOTCH ligand Delta-like 1 (DLL1. We show by mass spectral glycoproteomic analyses that DLL1 is O-fucosylated at the consensus motif C²XXXX(S/TC³ (where C² and C³ are the second and third conserved cysteines within the EGF repeats found in EGF repeats 3, 4, 7 and 8. A putative site with only three amino acids between the second cysteine and the hydroxy amino acid within EGF repeat 2 is not modified. DLL1 proteins with mutated O-fucosylation sites reach the cell surface and accumulate intracellularly. Likewise, in presomitic mesoderm cells of POFUT1 deficient embryos DLL1 is present on the cell surface, and in mouse embryonic fibroblasts lacking POFUT1 the same relative amount of overexpressed wild type DLL1 reaches the cell surface as in wild type embryonic fibroblasts. DLL1 expressed in POFUT1 mutant cells can activate NOTCH, indicating that POFUT1 is not required for DLL1 function as a Notch ligand.

  2. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

    NARCIS (Netherlands)

    Kapur, R.; Della Valle, L.; Verhagen, O.J.; Hipgrave Ederveen, A.; Ligthart, P.; de Haas, M.; Kumpel, B.; Wuhrer, M.; van der Schoot, C.E.; Vidarsson, G.

    2015-01-01

    Background RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions

  3. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D

    NARCIS (Netherlands)

    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J. H. M.; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C. Ellen; Vidarsson, Gestur

    2015-01-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with

  4. Dissecting cross-reactivity in hymenoptera venom allergy by circumvention of alpha-1,3-core fucosylation.

    Science.gov (United States)

    Seismann, Henning; Blank, Simon; Braren, Ingke; Greunke, Kerstin; Cifuentes, Liliana; Grunwald, Thomas; Bredehorst, Reinhard; Ollert, Markus; Spillner, Edzard

    2010-01-01

    Hymenoptera venom allergy is known to cause life-threatening and sometimes fatal IgE-mediated anaphylactic reactions in allergic individuals. About 30-50% of patients with insect venom allergy have IgE antibodies that react with both honeybee and yellow jacket venom. Apart from true double sensitisation, IgE against cross-reactive carbohydrate determinants (CCD) are the most frequent cause of multiple reactivities severely hampering the diagnosis and design of therapeutic strategies by clinically irrelevant test results. In this study we addressed allergenic cross-reactivity using a recombinant approach by employing cell lines with variant capacities of alpha-1,3-core fucosylation. The venom hyaluronidases, supposed major allergens implicated in cross-reactivity phenomena, from honeybee (Api m 2) and yellow jacket (Ves v 2a and its putative isoform Ves v 2b) as well as the human alpha-2HS-glycoprotein as control, were produced in different insect cell lines. In stark contrast to production in Trichoplusia ni (HighFive) cells, alpha-1,3-core fucosylation was absent or immunologically negligible after production in Spodoptera frugiperda (Sf9) cells. Consistently, co-expression of honeybee alpha-1,3-fucosyltransferase in Sf9 cells resulted in the reconstitution of CCD reactivity. Re-evaluation of differentially fucosylated hyaluronidases by screening of individual venom-sensitised sera emphasised the allergenic relevance of Api m 2 beyond its carbohydrate epitopes. In contrast, the vespid hyaluronidases, for which a predominance of Ves v 2b could be shown, exhibited pronounced and primary carbohydrate reactivity rendering their relevance in the context of allergy questionable. These findings show that the use of recombinant molecules devoid of CCDs represents a novel strategy with major implications for diagnostic and therapeutic approaches. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Local Administration of 2% Trimecaine Affects the Content of Fucosylated Glycoconjugates in Goblet Cells in Rabbit Tracheal Epithelium

    Czech Academy of Sciences Publication Activity Database

    Vajner, L.; Uhlík, J.; Konrádová, V.; Kleščová, A.; Adášková, Jana

    2006-01-01

    Roč. 87, č. 4 (2006), s. 283-288 ISSN 0959-9673 Source of funding: V - iné verejné zdroje Keywords : airway goblet cells * fucosylation * lectin histochemistry * rabbit model * trimecaine Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.707, year: 2006

  6. In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS) from Sea Cucumber Cucumaria frondosa.

    Science.gov (United States)

    Liu, Xiaoxiao; Liu, Yong; Hao, Jiejie; Zhao, Xiaoliang; Lang, Yinzhi; Fan, Fei; Cai, Chao; Li, Guoyun; Zhang, Lijuan; Yu, Guangli

    2016-05-12

    The low-molecular-weight fucosylated chondroitin sulfate (LFCS) was prepared from native fucosylated chondroitin sulfate (FCS), which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC) was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF), increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and downregulated the matrix metalloproteinases (MMPs) level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study.

  7. In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS from Sea Cucumber Cucumaria frondosa

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Liu

    2016-05-01

    Full Text Available The low-molecular-weight fucosylated chondroitin sulfate (LFCS was prepared from native fucosylated chondroitin sulfate (FCS, which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF, increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1 and downregulated the matrix metalloproteinases (MMPs level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study.

  8. The Effects of Intravenously Administrated Methylxanthines on the Proportion of Globlet Cells Containing Fucosylated Glycoconjugates in Rabbit Tracheal Epithelium

    Czech Academy of Sciences Publication Activity Database

    Vajner, L.; Konrádová, V.; Uhlík, J.; Adášková, Jana

    2004-01-01

    Roč. 106, č. 1 (2004), s. 47-54 ISSN 0065-1281 Source of funding: V - iné verejné zdroje Keywords : fucosylation * tracheal epithelium * lectin histochemistry * methylxanthines * rabbits Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.895, year: 2004

  9. Structural analysis and anticoagulant activities of two sulfated polysaccharides from the sea cucumber Holothuria coluber.

    Science.gov (United States)

    Yang, Wenjiao; Cai, Ying; Yin, Ronghua; Lin, Lisha; Li, Zhongkun; Wu, Mingyi; Zhao, Jinhua

    2018-05-01

    Sulfated polysaccharides such as fucosylated glycosaminoglycan and fucan sulfate from echinoderm possess complex chemical structure and various biological activities. The two sulfated polysaccharides were purified from the low-value sea cucumber Holothuria coluber. Their physicochemical properties and chemical structures were analyzed and characterized by chemical and instrumental methods. Structural analysis clarified that the sea cucumber fucosylated glycosaminoglycan contains a chondroitin sulfate-like backbone and fucosyl branches with four various sulfation patterns. The fucan sulfate with molecular weight of 64.6 kDa comprises a central core of regular α(1 → 4)-linked tetrasaccharide repeating units, each of which is linked by a 4-O-sulfated fucose residue. Anticoagulant assays indicated that these sulfated polysaccharides possessed strong APTT prolonging activities and intrinsic factor Xase inhibitory activities, both of which decreased with the reduction of their molecular weights. Our results expand knowledge on the structural types of sulfated polysaccharides from sea cucumbers and further illustrate their functionality. Copyright © 2018. Published by Elsevier B.V.

  10. Studies on the O-polysaccharide of Escherichia albertii O2 characterized by non-stoichiometric O-acetylation and non-stoichiometric side-chain l-fucosylation.

    Science.gov (United States)

    Naumenko, Olesya I; Zheng, Han; Xiong, Yanwen; Senchenkova, Sof'ya N; Wang, Hong; Shashkov, Alexander S; Li, Qun; Wang, Jianping; Knirel, Yuriy A

    2018-05-22

    An O-polysaccharide was isolated from the lipopolysaccharide of Escherichia albertii O2 and studied by chemical methods and 1D and 2D 1 H and 13 C NMR spectroscopy. The following structure of the O-polysaccharide was established: . The O-polysaccharide is characterized by masked regularity owing to a non-stoichiometric O-acetylation of an l-fucose residue in the main chain and a non-stoichiometric side-chain l-fucosylation of a β-GlcNAc residue. A regular linear polysaccharide was obtained by sequential Smith degradation and alkaline O-deacetylation of the O-polysaccharide. The content of the O-antigen gene cluster of E. albertii O2 was found to be essentially consistent with the O-polysaccharide structure established. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Protein structural similarity search by Ramachandran codes

    Directory of Open Access Journals (Sweden)

    Chang Chih-Hung

    2007-08-01

    Full Text Available Abstract Background Protein structural data has increased exponentially, such that fast and accurate tools are necessary to access structure similarity search. To improve the search speed, several methods have been designed to reduce three-dimensional protein structures to one-dimensional text strings that are then analyzed by traditional sequence alignment methods; however, the accuracy is usually sacrificed and the speed is still unable to match sequence similarity search tools. Here, we aimed to improve the linear encoding methodology and develop efficient search tools that can rapidly retrieve structural homologs from large protein databases. Results We propose a new linear encoding method, SARST (Structural similarity search Aided by Ramachandran Sequential Transformation. SARST transforms protein structures into text strings through a Ramachandran map organized by nearest-neighbor clustering and uses a regenerative approach to produce substitution matrices. Then, classical sequence similarity search methods can be applied to the structural similarity search. Its accuracy is similar to Combinatorial Extension (CE and works over 243,000 times faster, searching 34,000 proteins in 0.34 sec with a 3.2-GHz CPU. SARST provides statistically meaningful expectation values to assess the retrieved information. It has been implemented into a web service and a stand-alone Java program that is able to run on many different platforms. Conclusion As a database search method, SARST can rapidly distinguish high from low similarities and efficiently retrieve homologous structures. It demonstrates that the easily accessible linear encoding methodology has the potential to serve as a foundation for efficient protein structural similarity search tools. These search tools are supposed applicable to automated and high-throughput functional annotations or predictions for the ever increasing number of published protein structures in this post-genomic era.

  12. Processing of complex N-glycans in IgG Fc-region is affected by core fucosylation

    Science.gov (United States)

    Castilho, Alexandra; Gruber, Clemens; Thader, Andreas; Oostenbrink, Chris; Pechlaner, Maria; Steinkellner, Herta; Altmann, Friedrich

    2015-01-01

    We investigated N-glycan processing of immunoglobulin G1 using the monoclonal antibody cetuximab (CxMab), which has a glycosite in the Fab domain in addition to the conserved Fc glycosylation, as a reporter. Three GlcNAc (Gn) terminating bi-antennary glycoforms of CxMab differing in core fucosylation (α1,3- and α1,6-linkage) were generated in a plant-based expression platform. These GnGn, GnGnF3, and GnGnF6 CxMab variants were subjected in vivo to further processing toward sialylation and GlcNAc diversification (bisected and branching structures). Mass spectrometry-based glycan analyses revealed efficient processing of Fab glycans toward envisaged structures. By contrast, Fc glycan processing largely depend on the presence of core fucose. A particularly strong support of glycan processing in the presence of plant-specific core α1,3-fucose was observed. Consistently, molecular modeling suggests changes in the interactions of the Fc carbohydrate chain depending on the presence of core fucose, possibly changing the accessibility. Here, we provide data that reveal molecular mechanisms of glycan processing of IgG antibodies, which may have implications for the generation of glycan-engineered therapeutic antibodies with improved efficacies. PMID:26067753

  13. In vitro fermentation behaviors of fucosylated chondroitin sulfate from Pearsonothuria graeffei by human gut microflora.

    Science.gov (United States)

    Wei, Chao-Yang; Liao, Ning-Bo; Zhang, Yu; Ye, Xing-Qian; Li, Shan; Hu, Ya-Qin; Liu, Dong-Hong; Linhardt, Robert J; Wang, Xin; Chen, Shi-Guo

    2017-09-01

    A fucosylated chondroitin sulfate (FCS-pg) with highly repeated structure from Pearsonothuria graeffei was subjected to a in vitro fermentation model to investigate its fermentability and effects on human gut microflora. High performance liquid chromatography (HPLC) measurement found FCS-pg can be fermented to short chain fatty acids (SCFAs) by gut microflora from partial human fecal samples. 16S rRNA gene-based polymerase chain reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) profiling and real-time quantitative PCR analysis showed that FCS-pg mainly increased the proportions of Clostridium cluster XI, Bacteriodes prevotella group, Bifidobacterium genus, Clostridium cluster I and Clostridium cluster XIVab, whereas the numbers of the Enterobacteriaceae and Lactobacillus decreased. These results indicated that FCS-pg was mainly fermented by Bacteroides, Bifidobacterium and Clostridium. It increased the content of probiotics bacteria in achieving health-enhancing effect, was slightly different than most sulfated polysaccharides from marine animals. The current study provides useful new information on the mechanism of absorption and functional activity on FCS-pg within the gastrointestinal tract of the human body. Copyright © 2017. Published by Elsevier B.V.

  14. Discovering Music Structure via Similarity Fusion

    DEFF Research Database (Denmark)

    for representing music structure is studied in a simplified scenario consisting of 4412 songs and two similarity measures among them. The results suggest that the PLSA model is a useful framework to combine different sources of information, and provides a reasonable space for song representation.......Automatic methods for music navigation and music recommendation exploit the structure in the music to carry out a meaningful exploration of the “song space”. To get a satisfactory performance from such systems, one should incorporate as much information about songs similarity as possible; however...... semantics”, in such a way that all observed similarities can be satisfactorily explained using the latent semantics. Therefore, one can think of these semantics as the real structure in music, in the sense that they can explain the observed similarities among songs. The suitability of the PLSA model...

  15. Discovering Music Structure via Similarity Fusion

    DEFF Research Database (Denmark)

    Arenas-García, Jerónimo; Parrado-Hernandez, Emilio; Meng, Anders

    Automatic methods for music navigation and music recommendation exploit the structure in the music to carry out a meaningful exploration of the “song space”. To get a satisfactory performance from such systems, one should incorporate as much information about songs similarity as possible; however...... semantics”, in such a way that all observed similarities can be satisfactorily explained using the latent semantics. Therefore, one can think of these semantics as the real structure in music, in the sense that they can explain the observed similarities among songs. The suitability of the PLSA model...... for representing music structure is studied in a simplified scenario consisting of 4412 songs and two similarity measures among them. The results suggest that the PLSA model is a useful framework to combine different sources of information, and provides a reasonable space for song representation....

  16. In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the fucosyltransferase multigene family.

    Science.gov (United States)

    Peterson, Nathan A; Anderson, Tavis K; Yoshino, Timothy P

    2013-01-01

    Fucosylated glycans of the parasitic flatworm Schistosoma mansoni play key roles in its development and immunobiology. In the present study we used a genome-wide homology-based bioinformatics approach to search for genes that contribute to fucosylated glycan expression in S. mansoni, specifically the α2-, α3-, and α6-fucosyltransferases (FucTs), which transfer L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. We identified and in silico characterized several novel schistosome FucT homologs, including six α3-FucTs and six α6-FucTs, as well as two protein O-FucTs that catalyze the unrelated transfer of L-fucose to serine and threonine residues of epidermal growth factor- and thrombospondin-type repeats. No α2-FucTs were observed. Primary sequence analyses identified key conserved FucT motifs as well as characteristic transmembrane domains, consistent with their putative roles as fucosyltransferases. Most genes exhibit alternative splicing, with multiple transcript variants generated. A phylogenetic analysis demonstrated that schistosome α3- and α6-FucTs form monophyletic clades within their respective gene families, suggesting multiple gene duplications following the separation of the schistosome lineage from the main evolutionary tree. Quantitative decreases in steady-state transcript levels of some FucTs during early larval development suggest a possible mechanism for differential expression of fucosylated glycans in schistosomes. This study systematically identifies the complete repertoire of FucT homologs in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, developmental expression, and evolutionary history.

  17. Protein structure similarity from principle component correlation analysis

    Directory of Open Access Journals (Sweden)

    Chou James

    2006-01-01

    Full Text Available Abstract Background Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities. Results We measure structural similarity between proteins by correlating the principle components of their secondary structure interaction matrix. In our approach, the Principle Component Correlation (PCC analysis, a symmetric interaction matrix for a protein structure is constructed with relationship parameters between secondary elements that can take the form of distance, orientation, or other relevant structural invariants. When using a distance-based construction in the presence or absence of encoded N to C terminal sense, there are strong correlations between the principle components of interaction matrices of structurally or topologically similar proteins. Conclusion The PCC method is extensively tested for protein structures that belong to the same topological class but are significantly different by RMSD measure. The PCC analysis can also differentiate proteins having similar shapes but different topological arrangements. Additionally, we demonstrate that when using two independently defined interaction matrices, comparison of their maximum

  18. 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation

    Science.gov (United States)

    Wallace, Ian S.

    2015-01-01

    The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. In this study, we characterize novel small molecule inhibitors of plant fucosylation. 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. PMID:26414071

  19. 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation.

    Directory of Open Access Journals (Sweden)

    Jose A Villalobos

    Full Text Available The monosaccharide L-fucose (L-Fuc is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I and rhamnogalacturonan-II (RG-II, arabinogalactan proteins, and N-linked glycans. Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. In this study, we characterize novel small molecule inhibitors of plant fucosylation. 2-fluoro-L-fucose (2F-Fuc analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP, suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis.

  20. In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import.

    Science.gov (United States)

    Peterson, Nathan A; Anderson, Tavis K; Wu, Xiao-Jun; Yoshino, Timothy P

    2013-07-09

    Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous localization of highly

  1. Molecular size is important for the safety and selective inhibition of intrinsic factor Xase for fucosylated chondroitin sulfate.

    Science.gov (United States)

    Yan, Lufeng; Li, Junhui; Wang, Danli; Ding, Tian; Hu, Yaqin; Ye, Xingqian; Linhardt, Robert J; Chen, Shiguo

    2017-12-15

    Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (FCS-Ib) showed potent anticoagulant activities without selectivity. The present study focused on developing safe FCS-Ib oligomers showing selective inhibition of intrinsic factor Xase (anti-FXase) prepared through partial N-deacetylation-deaminative cleavage. The N-deacetylation degree was regulated by reaction time, controlling the resulting oligomer distribution. Structure analysis confirmed the selectivity of degradation, and 12 high purity fractions with trisaccharide-repeating units were separated. In vitro anticoagulant assays indicated a decrease in molecular weight (Mw) dramatically reduced activated partial thromboplastin time (APTT), thrombin time (TT), AT-dependent anti-FIIa and anti-FXa activities, while the oligomers retained potent anti-FXase activity until they fell below 3kDa. Meanwhile, human FXII activation and platelet aggregation were markedly reduced with decreasing Mw and were moderate when under 12.0kDa. Thus, fragments of 3-12.0kDa should be safe and effective as selective inhibitors of intrinsic tenase complex for application as clinical anticoagulants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Structural similarity and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B

    2004-01-01

    It has been suggested that category-specific recognition disorders for natural objects may reflect that natural objects are more structurally (visually) similar than artefacts and therefore more difficult to recognize following brain damage. On this account one might expect a positive relationshi...

  3. Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.

    Science.gov (United States)

    Li, Junhui; Li, Shan; Yan, Lufeng; Ding, Tian; Linhardt, Robert J; Yu, Yanlei; Liu, Xinyue; Liu, Donghong; Ye, Xingqian; Chen, Shiguo

    2017-10-20

    Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs. In vitro activities were measured by activated partial thromboplastin time (APTT), thrombin time (TT), thrombin and factor Xa inhibition, and activation of FXII. The results showed that free radicals preferentially acted on GlcA residues affording oligosaccharides that were purified from both fCSs. The inhibition of thrombin and factor X activities, mediated through antithrombin III and heparin cofactor II of fCSs oligosaccharides were affected by their molecular weight and fucose branches. Oligosaccharides with different sulfation patterns of the fucose branching had a similar ability to inhibit the FXa by the intrinsic factor Xase (factor IXa-VIIIa complex). Oligosaccharides with 2,4-O-sulfo fucose branches from fCS-Ib showed higher activities than ones with 3,4-O-disulfo branches obtained from fCS-Pg. Furthermore, a heptasaccharide is the minimum size oligosaccharide required for anticoagulation and FXII activation. This activity was absent for fCS oligosaccharides smaller than nonasaccharides. Molecular size and fucose branch sulfation are important for anticoagulant activity and reduction of size can reverse the activation of FXII caused by native fCSs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Sulfation pattern of fucose branches affects the anti-hyperlipidemic activities of fucosylated chondroitin sulfate.

    Science.gov (United States)

    Wu, Nian; Zhang, Yu; Ye, Xingqian; Hu, Yaqin; Ding, Tian; Chen, Shiguo

    2016-08-20

    Fucosylated chondroitin sulfates (fCSs) are glycosaminoglycans extracted from sea cucumbers, consisting of chondroitin sulfate E (CSE) backbones and sulfated fucose branches. The biological properties of fCSs could be affected by the sulfation pattern of their fucose branches. In the present study, two fCSs were isolated from sea cucumbers Isostichopus badionotus (fCS-Ib) and Pearsonothuria graeffei (fCS-Pg). Their monosaccharide compositions of glucuronic acid (GlcA), N-acetylgalactosamine (GalNAc), fucose (Fuc) and sulfate were at similar molar ratio with 1.0/0.7/0.9/3.1 for fCS-Ib and 1.0/0.8/1.5/2.6 for fCS-Pg. The two fCSs have different sulfation patterns on their fucose branches, fCS-Pg with 3,4-O-disulfation while fCS-Ib with 2,4-O-disulfation. Their antihyperlipidemic effects were compared using a high-fat high-fructose diet (HFFD)-fed C57BL/6J mice model. Both fCS-Ib and fCS-Pg had significant effects on lipid profile improvement, liver protection, blood glucose diminution and hepatic glycogen synthesis. Specifically, fCS-Pg with 3,4-O-disulfation fucose branches was more effective in reduction of blood cholesterol (TC), low density lipoprotein (LDL) and atherogenic index (AI). Our results indicate that both fCSs, especially fCS-Pg, could be used as a potential anti-hyperlipidemic drug. Copyright © 2016. Published by Elsevier Ltd.

  5. Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER

    Energy Technology Data Exchange (ETDEWEB)

    Smart, Oliver S., E-mail: osmart@globalphasing.com; Womack, Thomas O.; Flensburg, Claus; Keller, Peter; Paciorek, Włodek; Sharff, Andrew; Vonrhein, Clemens; Bricogne, Gérard [Global Phasing Ltd, Sheraton House, Castle Park, Cambridge CB3 0AX (United Kingdom)

    2012-04-01

    Local structural similarity restraints (LSSR) provide a novel method for exploiting NCS or structural similarity to an external target structure. Two examples are given where BUSTER re-refinement of PDB entries with LSSR produces marked improvements, enabling further structural features to be modelled. Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct ‘target’ structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less than 5.5 Å between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and @@target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -target enables the correct ligand-binding structure to be found, and http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand.

  6. Measuring structural similarity in large online networks.

    Science.gov (United States)

    Shi, Yongren; Macy, Michael

    2016-09-01

    Structural similarity based on bipartite graphs can be used to detect meaningful communities, but the networks have been tiny compared to massive online networks. Scalability is important in applications involving tens of millions of individuals with highly skewed degree distributions. Simulation analysis holding underlying similarity constant shows that two widely used measures - Jaccard index and cosine similarity - are biased by the distribution of out-degree in web-scale networks. However, an alternative measure, the Standardized Co-incident Ratio (SCR), is unbiased. We apply SCR to members of Congress, musical artists, and professional sports teams to show how massive co-following on Twitter can be used to map meaningful affiliations among cultural entities, even in the absence of direct connections to one another. Our results show how structural similarity can be used to map cultural alignments and demonstrate the potential usefulness of social media data in the study of culture, politics, and organizations across the social and behavioral sciences. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Quality assessment of protein model-structures based on structural and functional similarities.

    Science.gov (United States)

    Konopka, Bogumil M; Nebel, Jean-Christophe; Kotulska, Malgorzata

    2012-09-21

    Experimental determination of protein 3D structures is expensive, time consuming and sometimes impossible. A gap between number of protein structures deposited in the World Wide Protein Data Bank and the number of sequenced proteins constantly broadens. Computational modeling is deemed to be one of the ways to deal with the problem. Although protein 3D structure prediction is a difficult task, many tools are available. These tools can model it from a sequence or partial structural information, e.g. contact maps. Consequently, biologists have the ability to generate automatically a putative 3D structure model of any protein. However, the main issue becomes evaluation of the model quality, which is one of the most important challenges of structural biology. GOBA--Gene Ontology-Based Assessment is a novel Protein Model Quality Assessment Program. It estimates the compatibility between a model-structure and its expected function. GOBA is based on the assumption that a high quality model is expected to be structurally similar to proteins functionally similar to the prediction target. Whereas DALI is used to measure structure similarity, protein functional similarity is quantified using standardized and hierarchical description of proteins provided by Gene Ontology combined with Wang's algorithm for calculating semantic similarity. Two approaches are proposed to express the quality of protein model-structures. One is a single model quality assessment method, the other is its modification, which provides a relative measure of model quality. Exhaustive evaluation is performed on data sets of model-structures submitted to the CASP8 and CASP9 contests. The validation shows that the method is able to discriminate between good and bad model-structures. The best of tested GOBA scores achieved 0.74 and 0.8 as a mean Pearson correlation to the observed quality of models in our CASP8 and CASP9-based validation sets. GOBA also obtained the best result for two targets of CASP8, and

  8. Lipschitz equivalence of self-similar sets with touching structures

    International Nuclear Information System (INIS)

    Ruan, Huo-Jun; Wang, Yang; Xi, Li-Feng

    2014-01-01

    Lipschitz equivalence of self-similar sets is an important area in the study of fractal geometry. It is known that two dust-like self-similar sets with the same contraction ratios are always Lipschitz equivalent. However, when self-similar sets have touching structures the problem of Lipschitz equivalence becomes much more challenging and intriguing at the same time. So far, all the known results only cover self-similar sets in R with no more than three branches. In this study we establish results for the Lipschitz equivalence of self-similar sets with touching structures in R with arbitrarily many branches. Key to our study is the introduction of a geometric condition for self-similar sets called substitutable. (paper)

  9. Multi-scale structural similarity index for motion detection

    Directory of Open Access Journals (Sweden)

    M. Abdel-Salam Nasr

    2017-07-01

    Full Text Available The most recent approach for measuring the image quality is the structural similarity index (SSI. This paper presents a novel algorithm based on the multi-scale structural similarity index for motion detection (MS-SSIM in videos. The MS-SSIM approach is based on modeling of image luminance, contrast and structure at multiple scales. The MS-SSIM has resulted in much better performance than the single scale SSI approach but at the cost of relatively lower processing speed. The major advantages of the presented algorithm are both: the higher detection accuracy and the quasi real-time processing speed.

  10. GIS: a comprehensive source for protein structure similarities.

    Science.gov (United States)

    Guerler, Aysam; Knapp, Ernst-Walter

    2010-07-01

    A web service for analysis of protein structures that are sequentially or non-sequentially similar was generated. Recently, the non-sequential structure alignment algorithm GANGSTA+ was introduced. GANGSTA+ can detect non-sequential structural analogs for proteins stated to possess novel folds. Since GANGSTA+ ignores the polypeptide chain connectivity of secondary structure elements (i.e. alpha-helices and beta-strands), it is able to detect structural similarities also between proteins whose sequences were reshuffled during evolution. GANGSTA+ was applied in an all-against-all comparison on the ASTRAL40 database (SCOP version 1.75), which consists of >10,000 protein domains yielding about 55 x 10(6) possible protein structure alignments. Here, we provide the resulting protein structure alignments as a public web-based service, named GANGSTA+ Internet Services (GIS). We also allow to browse the ASTRAL40 database of protein structures with GANGSTA+ relative to an externally given protein structure using different constraints to select specific results. GIS allows us to analyze protein structure families according to the SCOP classification scheme. Additionally, users can upload their own protein structures for pairwise protein structure comparison, alignment against all protein structures of the ASTRAL40 database (SCOP version 1.75) or symmetry analysis. GIS is publicly available at http://agknapp.chemie.fu-berlin.de/gplus.

  11. The Similar Structures and Control Problems of Complex Systems

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In this paper, the naturally evolving complex systems, such as biotic and social ones, are considered. Focusing on their structures, a feature is noteworthy, i.e., the similarity in structures. The relations between the functions and behaviors of these systems and their similar structures will be studied. Owing to the management of social systems and the course of evolution of biotic systems may be regarded as control processes, the researches will be within the scope of control problems. Moreover, since it is difficult to model for biotic and social systems, it will start with the control problems of complex systems, possessing similar structures, in engineering.The obtained results show that for either linear or nonlinear systems and for a lot of control problemssimilar structures lead to a series of simplifications. In general, the original system may be decomposed into reduced amount of subsystems with lower dimensions and simpler structures. By virtue of such subsystems, the control problems of original system can be solved more simply.At last, it turns round to observe the biotic and social systems and some analyses are given.

  12. New serum markers for small-cell lung cancer. I. The ganglioside fucosyl-GM1

    DEFF Research Database (Denmark)

    Vangsted, A; Drivsholm, L; Andersen, E

    1994-01-01

    The ganglioside fucosyl-GM1 (FucGM1) has been suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analyses have shown the expression of the ganglioside in tumors in 75 to 90% of patients with SCLC. We have demonstrated that the ganglioside is shedded from SCLC cells both...... an immunoassay based on the scintillation proximity assay to analyze the concentrations of FucGM1 in sera from 112 SCLC patients, 21 patients with non-SCLC, 4 patients with other cancer forms, and 20 healthy controls. Sera were collected at the time of diagnosis before initiation of chemotherapy. The expression...... of FucGM1 was related to age, sex, blood group of the patient, and to the stage of disease and organ site involvement of metastases. The sera of 50% of the patients with SCLC were positive for FucGM1, and 12 of 21 sera from non-SCLC patients were markedly elevated. In SCLC sera, the concentration of Fuc...

  13. Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

    Science.gov (United States)

    Yee, Yohan; Fernandes, Darren J; French, Leon; Ellegood, Jacob; Cahill, Lindsay S; Vousden, Dulcie A; Spencer Noakes, Leigh; Scholz, Jan; van Eede, Matthijs C; Nieman, Brian J; Sled, John G; Lerch, Jason P

    2018-05-18

    An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the

  14. A method for rapid similarity analysis of RNA secondary structures

    Directory of Open Access Journals (Sweden)

    Liu Na

    2006-11-01

    Full Text Available Abstract Background Owing to the rapid expansion of RNA structure databases in recent years, efficient methods for structure comparison are in demand for function prediction and evolutionary analysis. Usually, the similarity of RNA secondary structures is evaluated based on tree models and dynamic programming algorithms. We present here a new method for the similarity analysis of RNA secondary structures. Results Three sets of real data have been used as input for the example applications. Set I includes the structures from 5S rRNAs. Set II includes the secondary structures from RNase P and RNase MRP. Set III includes the structures from 16S rRNAs. Reasonable phylogenetic trees are derived for these three sets of data by using our method. Moreover, our program runs faster as compared to some existing ones. Conclusion The famous Lempel-Ziv algorithm can efficiently extract the information on repeated patterns encoded in RNA secondary structures and makes our method an alternative to analyze the similarity of RNA secondary structures. This method will also be useful to researchers who are interested in evolutionary analysis.

  15. Rapid milk group classification by 1H NMR analysis of Le and H epitopes in human milk oligosaccharide donor samples

    NARCIS (Netherlands)

    van Leeuwen, Sander S; Schoemaker, Ruud J W; Gerwig, Gerrit J; van Leusen-van Kan, Ellen J M; Dijkhuizen, Lubbert; Kamerling, Johannis P

    Human milk oligosaccharides (HMOs) are a major constituent of human breast milk and play an important role in reducing the risk of infections in infants. The structures of these HMOs show similarities with blood group antigens in protein glycosylation, in particular in relation to fucosylation in

  16. Different measures of structural similarity tap different aspects of visual object processing

    DEFF Research Database (Denmark)

    Gerlach, Christian

    2017-01-01

    The structural similarity of objects has been an important variable in explaining why some objects are easier to categorize at a superordinate level than to individuate, and also why some patients with brain injury have more difficulties in recognizing natural (structurally similar) objects than...... artifacts (structurally distinct objects). In spite of its merits as an explanatory variable, structural similarity is not a unitary construct, and it has been operationalized in different ways. Furthermore, even though measures of structural similarity have been successful in explaining task and category-effects...

  17. Fc-Glycosylation in Human IgG1 and IgG3 Is Similar for Both Total and Anti-Red-Blood Cell Anti-K Antibodies

    Directory of Open Access Journals (Sweden)

    Myrthe E. Sonneveld

    2018-01-01

    Full Text Available After albumin, immunoglobulin G (IgG are the most abundant proteins in human serum, with IgG1 and IgG3 being the most abundant subclasses directed against protein antigens. The quality of the IgG-Fc-glycosylation has important functional consequences, which have been found to be skewed toward low fucosylation in some antigen-specific immune responses. This increases the affinity to IgG1-Fc-receptor (FcγRIIIa/b and thereby directly affects downstream effector functions and disease severity. To date, antigen-specific IgG-glycosylation have not been analyzed for IgG3. Here, we analyzed 30 pregnant women with anti-K alloantibodies from a prospective screening cohort and compared the type of Fc-tail glycosylation of total serum- and antigen-specific IgG1 and IgG3 using mass spectrometry. Total serum IgG1 and IgG3 Fc-glycoprofiles were highly similar. Fc glycosylation of antigen-specific IgG varied greatly between individuals, but correlated significantly with each other for IgG1 and IgG3, except for bisection. However, although the magnitude of changes in fucosylation and galactosylation were similar for both subclasses, this was not the case for sialylation levels, which were significantly higher for both total and anti-K IgG3. We found that the combination of relative IgG1 and IgG3 Fc-glycosylation levels did not improve the prediction of anti-K mediated disease over IgG1 alone. In conclusion, Fc-glycosylation profiles of serum- and antigen-specific IgG1 and IgG3 are highly similar.

  18. Musical structure analysis using similarity matrix and dynamic programming

    Science.gov (United States)

    Shiu, Yu; Jeong, Hong; Kuo, C.-C. Jay

    2005-10-01

    Automatic music segmentation and structure analysis from audio waveforms based on a three-level hierarchy is examined in this research, where the three-level hierarchy includes notes, measures and parts. The pitch class profile (PCP) feature is first extracted at the note level. Then, a similarity matrix is constructed at the measure level, where a dynamic time warping (DTW) technique is used to enhance the similarity computation by taking the temporal distortion of similar audio segments into account. By processing the similarity matrix, we can obtain a coarse-grain music segmentation result. Finally, dynamic programming is applied to the coarse-grain segments so that a song can be decomposed into several major parts such as intro, verse, chorus, bridge and outro. The performance of the proposed music structure analysis system is demonstrated for pop and rock music.

  19. Unveiling Music Structure Via PLSA Similarity Fusion

    DEFF Research Database (Denmark)

    Arenas-García, Jerónimo; Meng, Anders; Petersen, Kaare Brandt

    2007-01-01

    Nowadays there is an increasing interest in developing methods for building music recommendation systems. In order to get a satisfactory performance from such a system, one needs to incorporate as much information about songs similarity as possible; however, how to do so is not obvious. In this p......Nowadays there is an increasing interest in developing methods for building music recommendation systems. In order to get a satisfactory performance from such a system, one needs to incorporate as much information about songs similarity as possible; however, how to do so is not obvious...... observed similarities can be satisfactorily explained using the latent semantics. Additionally, this approach significantly simplifies the song retrieval phase, leading to a more practical system implementation. The suitability of the PLSA model for representing music structure is studied in a simplified...

  20. APPLICABILITY OF SIMILARITY CONDITIONS TO ANALOGUE MODELLING OF TECTONIC STRUCTURES

    Directory of Open Access Journals (Sweden)

    Mikhail A. Goncharov

    2010-01-01

    Full Text Available The publication is aimed at comparing concepts of V.V. Belousov and M.V. Gzovsky, outstanding researchers who established fundamentals of tectonophysics in Russia, specifically similarity conditions in application to tectonophysical modeling. Quotations from their publications illustrate differences in their views. In this respect, we can reckon V.V. Belousov as a «realist» as he supported «the liberal point of view» [Methods of modelling…, 1988, p. 21–22], whereas M.V. Gzovsky can be regarded as an «idealist» as he believed that similarity conditions should be mandatorily applied to ensure correctness of physical modeling of tectonic deformations and structures [Gzovsky, 1975, pp. 88 and 94].Objectives of the present publication are (1 to be another reminder about desirability of compliance with similarity conditions in experimental tectonics; (2 to point out difficulties in ensuring such compliance; (3 to give examples which bring out the fact that similarity conditions are often met per se, i.e. automatically observed; (4 to show that modeling can be simplified in some cases without compromising quantitative estimations of parameters of structure formation.(1 Physical modelling of tectonic deformations and structures should be conducted, if possible, in compliance with conditions of geometric and physical similarity between experimental models and corresponding natural objects. In any case, a researcher should have a clear vision of conditions applicable to each particular experiment.(2 Application of similarity conditions is often challenging due to unavoidable difficulties caused by the following: a Imperfection of experimental equipment and technologies (Fig. 1 to 3; b uncertainties in estimating parameters of formation of natural structures, including main ones: structure size (Fig. 4, time of formation (Fig. 5, deformation properties of the medium wherein such structures are formed, including, first of all, viscosity (Fig. 6

  1. Fucosylated chondroitin sulfate is covalently associated with collagen fibrils in sea cucumber Apostichopus japonicus body wall.

    Science.gov (United States)

    Wang, Jun; Chang, Yaoguang; Wu, Fanxiu; Xu, Xiaoqi; Xue, Changhu

    2018-04-15

    Fucosylated chondroitin sulfate (fCS) is the major carbohydrate constituent of sea cucumber. However, the distribution of fCS in the sea cucumber body wall has not been fully described. We addressed this in the present study employing Apostichopus japonicus as the material, a sea cucumber species with significant commercial importance. It was found that fCS was covalently attached to collagen fibrils via O-glycosidic linkages. Transmission electron microscopy analysis revealed that fCS precipitate was present in gap regions of collagen fibrils as roughly globular or ellipsoidal dots. The fCS dots arranged circumferentially around the fibrils with an axial repeat period that matched the periodicity of the fibrils. Physicochemical analysis indicated that the presence of fCS significantly increased the negative charge of the fibrils. These findings provide novel insight into fCS distribution in the sea cucumber body wall and its supramolecular organization with other macromolecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Thai Language Sentence Similarity Computation Based on Syntactic Structure and Semantic Vector

    Science.gov (United States)

    Wang, Hongbin; Feng, Yinhan; Cheng, Liang

    2018-03-01

    Sentence similarity computation plays an increasingly important role in text mining, Web page retrieval, machine translation, speech recognition and question answering systems. Thai language as a kind of resources scarce language, it is not like Chinese language with HowNet and CiLin resources. So the Thai sentence similarity research faces some challenges. In order to solve this problem of the Thai language sentence similarity computation. This paper proposes a novel method to compute the similarity of Thai language sentence based on syntactic structure and semantic vector. This method firstly uses the Part-of-Speech (POS) dependency to calculate two sentences syntactic structure similarity, and then through the word vector to calculate two sentences semantic similarity. Finally, we combine the two methods to calculate two Thai language sentences similarity. The proposed method not only considers semantic, but also considers the sentence syntactic structure. The experiment result shows that this method in Thai language sentence similarity computation is feasible.

  3. A Structural-Lexical Measure of Semantic Similarity for Geo-Knowledge Graphs

    Directory of Open Access Journals (Sweden)

    Andrea Ballatore

    2015-04-01

    Full Text Available Graphs have become ubiquitous structures to encode geographic knowledge online. The Semantic Web’s linked open data, folksonomies, wiki websites and open gazetteers can be seen as geo-knowledge graphs, that is labeled graphs whose vertices represent geographic concepts and whose edges encode the relations between concepts. To compute the semantic similarity of concepts in such structures, this article defines the network-lexical similarity measure (NLS. This measure estimates similarity by combining two complementary sources of information: the network similarity of vertices and the semantic similarity of the lexical definitions. NLS is evaluated on the OpenStreetMap Semantic Network, a crowdsourced geo-knowledge graph that describes geographic concepts. The hybrid approach outperforms both network and lexical measures, obtaining very strong correlation with the similarity judgments of human subjects.

  4. An approach to large scale identification of non-obvious structural similarities between proteins

    Science.gov (United States)

    Cherkasov, Artem; Jones, Steven JM

    2004-01-01

    Background A new sequence independent bioinformatics approach allowing genome-wide search for proteins with similar three dimensional structures has been developed. By utilizing the numerical output of the sequence threading it establishes putative non-obvious structural similarities between proteins. When applied to the testing set of proteins with known three dimensional structures the developed approach was able to recognize structurally similar proteins with high accuracy. Results The method has been developed to identify pathogenic proteins with low sequence identity and high structural similarity to host analogues. Such protein structure relationships would be hypothesized to arise through convergent evolution or through ancient horizontal gene transfer events, now undetectable using current sequence alignment techniques. The pathogen proteins, which could mimic or interfere with host activities, would represent candidate virulence factors. The developed approach utilizes the numerical outputs from the sequence-structure threading. It identifies the potential structural similarity between a pair of proteins by correlating the threading scores of the corresponding two primary sequences against the library of the standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity in distinguishing protein pairs with high structural similarity. Conclusion Preliminary results obtained by comparison of the genomes of Homo sapiens and several strains of Chlamydia trachomatis have demonstrated the potential usefulness of the method in the identification of bacterial proteins with known or potential roles in virulence. PMID:15147578

  5. An approach to large scale identification of non-obvious structural similarities between proteins

    Directory of Open Access Journals (Sweden)

    Cherkasov Artem

    2004-05-01

    Full Text Available Abstract Background A new sequence independent bioinformatics approach allowing genome-wide search for proteins with similar three dimensional structures has been developed. By utilizing the numerical output of the sequence threading it establishes putative non-obvious structural similarities between proteins. When applied to the testing set of proteins with known three dimensional structures the developed approach was able to recognize structurally similar proteins with high accuracy. Results The method has been developed to identify pathogenic proteins with low sequence identity and high structural similarity to host analogues. Such protein structure relationships would be hypothesized to arise through convergent evolution or through ancient horizontal gene transfer events, now undetectable using current sequence alignment techniques. The pathogen proteins, which could mimic or interfere with host activities, would represent candidate virulence factors. The developed approach utilizes the numerical outputs from the sequence-structure threading. It identifies the potential structural similarity between a pair of proteins by correlating the threading scores of the corresponding two primary sequences against the library of the standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity in distinguishing protein pairs with high structural similarity. Conclusion Preliminary results obtained by comparison of the genomes of Homo sapiens and several strains of Chlamydia trachomatis have demonstrated the potential usefulness of the method in the identification of bacterial proteins with known or potential roles in virulence.

  6. A Feature-Based Structural Measure: An Image Similarity Measure for Face Recognition

    Directory of Open Access Journals (Sweden)

    Noor Abdalrazak Shnain

    2017-08-01

    Full Text Available Facial recognition is one of the most challenging and interesting problems within the field of computer vision and pattern recognition. During the last few years, it has gained special attention due to its importance in relation to current issues such as security, surveillance systems and forensics analysis. Despite this high level of attention to facial recognition, the success is still limited by certain conditions; there is no method which gives reliable results in all situations. In this paper, we propose an efficient similarity index that resolves the shortcomings of the existing measures of feature and structural similarity. This measure, called the Feature-Based Structural Measure (FSM, combines the best features of the well-known SSIM (structural similarity index measure and FSIM (feature similarity index measure approaches, striking a balance between performance for similar and dissimilar images of human faces. In addition to the statistical structural properties provided by SSIM, edge detection is incorporated in FSM as a distinctive structural feature. Its performance is tested for a wide range of PSNR (peak signal-to-noise ratio, using ORL (Olivetti Research Laboratory, now AT&T Laboratory Cambridge and FEI (Faculty of Industrial Engineering, São Bernardo do Campo, São Paulo, Brazil databases. The proposed measure is tested under conditions of Gaussian noise; simulation results show that the proposed FSM outperforms the well-known SSIM and FSIM approaches in its efficiency of similarity detection and recognition of human faces.

  7. Self-similar structure in the distribution and density of the partition function zeros

    International Nuclear Information System (INIS)

    Huang, M.-C.; Luo, Y.-P.; Liaw, T.-M.

    2003-01-01

    Based on the knowledge of the partition function zeros for the cell-decorated triangular Ising model, we analyze the similar structures contained in the distribution pattern and density function of the zeros. The two own the same symmetries, and the arising of the similar structure in the road toward the infinite decoration-level is exhibited explicitly. The distinct features of the formation of the self-similar structure revealed from this model may be quite general

  8. Similarity of High-Resolution Tandem Mass Spectrometry Spectra of Structurally Related Micropollutants and Transformation Products

    Science.gov (United States)

    Schollée, Jennifer E.; Schymanski, Emma L.; Stravs, Michael A.; Gulde, Rebekka; Thomaidis, Nikolaos S.; Hollender, Juliane

    2017-12-01

    High-resolution tandem mass spectrometry (HRMS2) with electrospray ionization is frequently applied to study polar organic molecules such as micropollutants. Fragmentation provides structural information to confirm structures of known compounds or propose structures of unknown compounds. Similarity of HRMS2 spectra between structurally related compounds has been suggested to facilitate identification of unknown compounds. To test this hypothesis, the similarity of reference standard HRMS2 spectra was calculated for 243 pairs of micropollutants and their structurally related transformation products (TPs); for comparison, spectral similarity was also calculated for 219 pairs of unrelated compounds. Spectra were measured on Orbitrap and QTOF mass spectrometers and similarity was calculated with the dot product. The influence of different factors on spectral similarity [e.g., normalized collision energy (NCE), merging fragments from all NCEs, and shifting fragments by the mass difference of the pair] was considered. Spectral similarity increased at higher NCEs and highest similarity scores for related pairs were obtained with merged spectra including measured fragments and shifted fragments. Removal of the monoisotopic peak was critical to reduce false positives. Using a spectral similarity score threshold of 0.52, 40% of related pairs and 0% of unrelated pairs were above this value. Structural similarity was estimated with the Tanimoto coefficient and pairs with higher structural similarity generally had higher spectral similarity. Pairs where one or both compounds contained heteroatoms such as sulfur often resulted in dissimilar spectra. This work demonstrates that HRMS2 spectral similarity may indicate structural similarity and that spectral similarity can be used in the future to screen complex samples for related compounds such as micropollutants and TPs, assisting in the prioritization of non-target compounds. [Figure not available: see fulltext.

  9. Fast protein tertiary structure retrieval based on global surface shape similarity.

    Science.gov (United States)

    Sael, Lee; Li, Bin; La, David; Fang, Yi; Ramani, Karthik; Rustamov, Raif; Kihara, Daisuke

    2008-09-01

    Characterization and identification of similar tertiary structure of proteins provides rich information for investigating function and evolution. The importance of structure similarity searches is increasing as structure databases continue to expand, partly due to the structural genomics projects. A crucial drawback of conventional protein structure comparison methods, which compare structures by their main-chain orientation or the spatial arrangement of secondary structure, is that a database search is too slow to be done in real-time. Here we introduce a global surface shape representation by three-dimensional (3D) Zernike descriptors, which represent a protein structure compactly as a series expansion of 3D functions. With this simplified representation, the search speed against a few thousand structures takes less than a minute. To investigate the agreement between surface representation defined by 3D Zernike descriptor and conventional main-chain based representation, a benchmark was performed against a protein classification generated by the combinatorial extension algorithm. Despite the different representation, 3D Zernike descriptor retrieved proteins of the same conformation defined by combinatorial extension in 89.6% of the cases within the top five closest structures. The real-time protein structure search by 3D Zernike descriptor will open up new possibility of large-scale global and local protein surface shape comparison. 2008 Wiley-Liss, Inc.

  10. Structural similarities between prokaryotic and eukaryotic 5S ribosomal RNAs

    International Nuclear Information System (INIS)

    Welfle, H.; Boehm, S.; Damaschun, G.; Fabian, H.; Gast, K.; Misselwitz, R.; Mueller, J.J.; Zirwer, D.; Filimonov, V.V.; Venyaminov, S.Yu.; Zalkova, T.N.

    1986-01-01

    5S RNAs from rat liver and E. coli have been studied by diffuse X-ray and dynamic light scattering and by infrared and Raman spectroscopy. Identical structures at a resolution of 1 nm can be deduced from the comparison of the experimental X-ray scattering curves and electron distance distribution functions and from the agreement of the shape parameters. A flat shape model with a compact central region and two protruding arms was derived. Double helical stems are eleven-fold helices with a mean base pair distance of 0.28 nm. The number of base pairs (26 GC, 9 AU for E. coli; 27 GC, 9 AU for rat liver) and the degree of base stacking are the same within the experimental error. A very high regularity in the ribophosphate backbone is indicated for both 5S RNAs. The observed structural similarity and the consensus secondary structure pattern derived from comparative sequence analyses suggest the conclusion that prokaryotic and eukaryotic 5S RNAs are in general very similar with respect to their fundamental structural features. (author)

  11. An enzymatic deglycosylation scheme enabling identification of core fucosylated N-glycans and O-glycosylation site mapping of human plasma proteins

    DEFF Research Database (Denmark)

    Hägglund, Per; Matthiesen, R.; Elortza, F.

    2007-01-01

    and N-acetyl-β-glucosaminidase) are also included. The two strategies were here applied to identify 103 N-glycosylation sites in the Cohn IV fraction of human plasma. In addition, Endo D/H digestion uniquely enabled identification of 23 fucosylated N-glycosylation sites. Several O-glycosylated peptides......, thereby reducing the complexity and facilitating glycosylation site determinations. Here, we have used two different enzymatic deglycosylation strategies for N-glycosylation site analysis. (1) Removal of entire N-glycan chains by peptide- N-glycosidase (PNGase) digestion, with concomitant deamidation...... of the released asparagine residue. The reaction is carried out in H218O to facilitate identification of the formerly glycosylated peptide by incorporatation of 18O into the formed aspartic acid residue. (2) Digestion with two endo-β- N-acetylglucosaminidases (Endo D and Endo H) that cleave the glycosidic bond...

  12. Discrete Self-Similarity in Interfacial Hydrodynamics and the Formation of Iterated Structures.

    Science.gov (United States)

    Dallaston, Michael C; Fontelos, Marco A; Tseluiko, Dmitri; Kalliadasis, Serafim

    2018-01-19

    The formation of iterated structures, such as satellite and subsatellite drops, filaments, and bubbles, is a common feature in interfacial hydrodynamics. Here we undertake a computational and theoretical study of their origin in the case of thin films of viscous fluids that are destabilized by long-range molecular or other forces. We demonstrate that iterated structures appear as a consequence of discrete self-similarity, where certain patterns repeat themselves, subject to rescaling, periodically in a logarithmic time scale. The result is an infinite sequence of ridges and filaments with similarity properties. The character of these discretely self-similar solutions as the result of a Hopf bifurcation from ordinarily self-similar solutions is also described.

  13. Local-global alignment for finding 3D similarities in protein structures

    Science.gov (United States)

    Zemla, Adam T [Brentwood, CA

    2011-09-20

    A method of finding 3D similarities in protein structures of a first molecule and a second molecule. The method comprises providing preselected information regarding the first molecule and the second molecule. Comparing the first molecule and the second molecule using Longest Continuous Segments (LCS) analysis. Comparing the first molecule and the second molecule using Global Distance Test (GDT) analysis. Comparing the first molecule and the second molecule using Local Global Alignment Scoring function (LGA_S) analysis. Verifying constructed alignment and repeating the steps to find the regions of 3D similarities in protein structures.

  14. Cloud4Psi: cloud computing for 3D protein structure similarity searching.

    Science.gov (United States)

    Mrozek, Dariusz; Małysiak-Mrozek, Bożena; Kłapciński, Artur

    2014-10-01

    Popular methods for 3D protein structure similarity searching, especially those that generate high-quality alignments such as Combinatorial Extension (CE) and Flexible structure Alignment by Chaining Aligned fragment pairs allowing Twists (FATCAT) are still time consuming. As a consequence, performing similarity searching against large repositories of structural data requires increased computational resources that are not always available. Cloud computing provides huge amounts of computational power that can be provisioned on a pay-as-you-go basis. We have developed the cloud-based system that allows scaling of the similarity searching process vertically and horizontally. Cloud4Psi (Cloud for Protein Similarity) was tested in the Microsoft Azure cloud environment and provided good, almost linearly proportional acceleration when scaled out onto many computational units. Cloud4Psi is available as Software as a Service for testing purposes at: http://cloud4psi.cloudapp.net/. For source code and software availability, please visit the Cloud4Psi project home page at http://zti.polsl.pl/dmrozek/science/cloud4psi.htm. © The Author 2014. Published by Oxford University Press.

  15. ProCKSI: a decision support system for Protein (Structure Comparison, Knowledge, Similarity and Information

    Directory of Open Access Journals (Sweden)

    Błażewicz Jacek

    2007-10-01

    Full Text Available Abstract Background We introduce the decision support system for Protein (Structure Comparison, Knowledge, Similarity and Information (ProCKSI. ProCKSI integrates various protein similarity measures through an easy to use interface that allows the comparison of multiple proteins simultaneously. It employs the Universal Similarity Metric (USM, the Maximum Contact Map Overlap (MaxCMO of protein structures and other external methods such as the DaliLite and the TM-align methods, the Combinatorial Extension (CE of the optimal path, and the FAST Align and Search Tool (FAST. Additionally, ProCKSI allows the user to upload a user-defined similarity matrix supplementing the methods mentioned, and computes a similarity consensus in order to provide a rich, integrated, multicriteria view of large datasets of protein structures. Results We present ProCKSI's architecture and workflow describing its intuitive user interface, and show its potential on three distinct test-cases. In the first case, ProCKSI is used to evaluate the results of a previous CASP competition, assessing the similarity of proposed models for given targets where the structures could have a large deviation from one another. To perform this type of comparison reliably, we introduce a new consensus method. The second study deals with the verification of a classification scheme for protein kinases, originally derived by sequence comparison by Hanks and Hunter, but here we use a consensus similarity measure based on structures. In the third experiment using the Rost and Sander dataset (RS126, we investigate how a combination of different sets of similarity measures influences the quality and performance of ProCKSI's new consensus measure. ProCKSI performs well with all three datasets, showing its potential for complex, simultaneous multi-method assessment of structural similarity in large protein datasets. Furthermore, combining different similarity measures is usually more robust than

  16. Examining Similarity Structure: Multidimensional Scaling and Related Approaches in Neuroimaging

    Directory of Open Access Journals (Sweden)

    Svetlana V. Shinkareva

    2013-01-01

    Full Text Available This paper covers similarity analyses, a subset of multivariate pattern analysis techniques that are based on similarity spaces defined by multivariate patterns. These techniques offer several advantages and complement other methods for brain data analyses, as they allow for comparison of representational structure across individuals, brain regions, and data acquisition methods. Particular attention is paid to multidimensional scaling and related approaches that yield spatial representations or provide methods for characterizing individual differences. We highlight unique contributions of these methods by reviewing recent applications to functional magnetic resonance imaging data and emphasize areas of caution in applying and interpreting similarity analysis methods.

  17. Structure modulates similarity-based interference in sluicing: An eye tracking study.

    Directory of Open Access Journals (Sweden)

    Jesse A. Harris

    2015-12-01

    Full Text Available In cue-based content-addressable approaches to memory, a target and its competitors are retrieved in parallel from memory via a fast, associative cue-matching procedure under a severely limited focus of attention. Such a parallel matching procedure could in principle ignore the serial order or hierarchical structure characteristic of linguistic relations. I present an eye tracking while reading experiment that investigates whether the sentential position of a potential antecedent modulates the strength of similarity-based interference, a well-studied effect in which increased similarity in features between a target and its competitors results in slower and less accurate retrieval overall. The manipulation trades on an independently established Locality bias in sluiced structures to associate a wh-remnant (which ones in clausal ellipsis with the most local correlate (some wines, as in The tourists enjoyed some wines, but I don’t know which ones. The findings generally support cue-based parsing models of sentence processing that are subject to similarity-based interference in retrieval, and provide additional support to the growing body of evidence that retrieval is sensitive to both the structural position of a target antecedent and its competitors, and the specificity of retrieval cues.

  18. Strategic Planning Process and Organizational Structure: Impacts, Confluence and Similarities

    Directory of Open Access Journals (Sweden)

    Dyogo Felype Neis

    2017-01-01

    Full Text Available This article aims to analyze the relationship between the strategic planning process and organizational structure in the reality of a complex organization: the Public Prosecutor’s Office of Santa Catarina (MPSC. The research is set by the single case study research strategy and data were collected through the following instruments: bibliographical research, documentary research, semi-structured interviews and systematic observation. The conclusion indicates that the phases of the strategic planning process influence and are influenced by the elements of the organizational structure and highlights the confluences, the impacts and similarities between the stages of formulation and implementation of the strategic process with the various constituent elements of the organizational structure.

  19. Fucosylated chondroitin sulfates from the body wall of the sea cucumber Holothuria forskali: conformation, selectin binding, and biological activity.

    Science.gov (United States)

    Panagos, Charalampos G; Thomson, Derek S; Moss, Claire; Hughes, Adam D; Kelly, Maeve S; Liu, Yan; Chai, Wengang; Venkatasamy, Radhakrishnan; Spina, Domenico; Page, Clive P; Hogwood, John; Woods, Robert J; Mulloy, Barbara; Bavington, Charlie D; Uhrín, Dušan

    2014-10-10

    Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: → 3)GalNAcβ4,6S(1 → 4) [FucαX(1 → 3)]GlcAβ(1 →, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Le(x) blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu(2+)-catalyzed Fenton-type and photochemical depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

    Science.gov (United States)

    Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

    2017-04-03

    Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

  1. Similarity Structure of Wave-Collapse

    DEFF Research Database (Denmark)

    Rypdal, Kristoffer; Juul Rasmussen, Jens; Thomsen, Kenneth

    1985-01-01

    Similarity transformations of the cubic Schrödinger equation (CSE) are investigated. The transformations are used to remove the explicit time variation in the CSE and reduce it to differential equations in the spatial variables only. Two different methods for similarity reduction are employed and...

  2. A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose branch exhibits neurite outgrowth-promoting activity: Novel biological roles of fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Shida, Miharu; Mikami, Tadahisa; Tamura, Jun-Ichi; Kitagawa, Hiroshi

    2017-06-03

    Chondroitin sulfate (CS) is a class of sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide unit composed of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). CS chains are found throughout the pericellular and extracellular spaces and contribute to the formation of functional microenvironments for numerous biological events. However, their structure-function relations remain to be fully characterized. Here, a fucosylated CS (FCS) was isolated from the body wall of the sea cucumber Apostichopus japonicus. Its promotional effects on neurite outgrowth were assessed by using isolated polysaccharides and the chemically synthesized FCS trisaccharide β-D-GalNAc(4,6-O-disulfate) (1-4)[α-l-fucose (2,4-O-disulfate) (1-3)]-β-D-GlcA. FCS polysaccharides contained the E-type disaccharide unit GlcA-GalNAc(4,6-O-disulfate) as a CS major backbone structure and carried distinct sulfated fucose branches. Despite their relatively lower abundance of E unit, FCS polysaccharides exhibited neurite outgrowth-promoting activity comparable to squid cartilage-derived CS-E polysaccharides, which are characterized by their predominant E units, suggesting potential roles of the fucose branch in neurite outgrowth. Indeed, the chemically synthesized FCS trisaccharide was as effective as CS-E tetrasaccharide in stimulating neurite elongation in vitro. In conclusion, FCS trisaccharide units with 2,4-O-disulfated fucose branches may provide new insights into understanding the structure-function relations of CS chains. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Multidrug transporters from bacteria to man : similarities in structure and function

    NARCIS (Netherlands)

    van Veen, HW; Konings, WN

    Organisms ranging from bacteria to man possess transmembrane transporters which confer resistance to toxic corn pounds. Underlining their biological significance, prokaryotic and eukaryotic multidrug transport proteins are very similar in structure and function. Therefore, a study of the factors

  4. Weighted similarity-based clustering of chemical structures and bioactivity data in early drug discovery.

    Science.gov (United States)

    Perualila-Tan, Nolen Joy; Shkedy, Ziv; Talloen, Willem; Göhlmann, Hinrich W H; Moerbeke, Marijke Van; Kasim, Adetayo

    2016-08-01

    The modern process of discovering candidate molecules in early drug discovery phase includes a wide range of approaches to extract vital information from the intersection of biology and chemistry. A typical strategy in compound selection involves compound clustering based on chemical similarity to obtain representative chemically diverse compounds (not incorporating potency information). In this paper, we propose an integrative clustering approach that makes use of both biological (compound efficacy) and chemical (structural features) data sources for the purpose of discovering a subset of compounds with aligned structural and biological properties. The datasets are integrated at the similarity level by assigning complementary weights to produce a weighted similarity matrix, serving as a generic input in any clustering algorithm. This new analysis work flow is semi-supervised method since, after the determination of clusters, a secondary analysis is performed wherein it finds differentially expressed genes associated to the derived integrated cluster(s) to further explain the compound-induced biological effects inside the cell. In this paper, datasets from two drug development oncology projects are used to illustrate the usefulness of the weighted similarity-based clustering approach to integrate multi-source high-dimensional information to aid drug discovery. Compounds that are structurally and biologically similar to the reference compounds are discovered using this proposed integrative approach.

  5. Self-similarities of periodic structures for a discrete model of a two-gene system

    International Nuclear Information System (INIS)

    Souza, S.L.T. de; Lima, A.A.; Caldas, I.L.; Medrano-T, R.O.; Guimarães-Filho, Z.O.

    2012-01-01

    We report self-similar properties of periodic structures remarkably organized in the two-parameter space for a two-gene system, described by two-dimensional symmetric map. The map consists of difference equations derived from the chemical reactions for gene expression and regulation. We characterize the system by using Lyapunov exponents and isoperiodic diagrams identifying periodic windows, denominated Arnold tongues and shrimp-shaped structures. Period-adding sequences are observed for both periodic windows. We also identify Fibonacci-type series and Golden ratio for Arnold tongues, and period multiple-of-three windows for shrimps. -- Highlights: ► The existence of noticeable periodic windows has been reported recently for several nonlinear systems. ► The periodic window distributions appear highly organized in two-parameter space. ► We characterize self-similar properties of Arnold tongues and shrimps for a two-gene model. ► We determine the period of the Arnold tongues recognizing a Fibonacci-type sequence. ► We explore self-similar features of the shrimps identifying multiple period-three structures.

  6. Self-similarities of periodic structures for a discrete model of a two-gene system

    Energy Technology Data Exchange (ETDEWEB)

    Souza, S.L.T. de, E-mail: thomaz@ufsj.edu.br [Departamento de Física e Matemática, Universidade Federal de São João del-Rei, Ouro Branco, MG (Brazil); Lima, A.A. [Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Caldas, I.L. [Instituto de Física, Universidade de São Paulo, São Paulo, SP (Brazil); Medrano-T, R.O. [Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Diadema, SP (Brazil); Guimarães-Filho, Z.O. [Aix-Marseille Univ., CNRS PIIM UMR6633, International Institute for Fusion Science, Marseille (France)

    2012-03-12

    We report self-similar properties of periodic structures remarkably organized in the two-parameter space for a two-gene system, described by two-dimensional symmetric map. The map consists of difference equations derived from the chemical reactions for gene expression and regulation. We characterize the system by using Lyapunov exponents and isoperiodic diagrams identifying periodic windows, denominated Arnold tongues and shrimp-shaped structures. Period-adding sequences are observed for both periodic windows. We also identify Fibonacci-type series and Golden ratio for Arnold tongues, and period multiple-of-three windows for shrimps. -- Highlights: ► The existence of noticeable periodic windows has been reported recently for several nonlinear systems. ► The periodic window distributions appear highly organized in two-parameter space. ► We characterize self-similar properties of Arnold tongues and shrimps for a two-gene model. ► We determine the period of the Arnold tongues recognizing a Fibonacci-type sequence. ► We explore self-similar features of the shrimps identifying multiple period-three structures.

  7. Structural similarities in DNA packaging and delivery apparatuses in Herpesvirus and dsDNA bacteriophages.

    Science.gov (United States)

    Rixon, Frazer J; Schmid, Michael F

    2014-04-01

    Structural information can inform our understanding of virus origins and evolution. The herpesviruses and tailed bacteriophages constitute two large families of dsDNA viruses which infect vertebrates and prokaryotes respectively. A relationship between these disparate groups was initially suggested by similarities in their capsid assembly and DNA packaging strategies. This relationship has now been confirmed by a range of studies that have revealed common structural features in their capsid proteins, and similar organizations and sequence conservation in their DNA packaging machinery and maturational proteases. This concentration of conserved traits in proteins involved in essential and primordial capsid/packaging functions is evidence that these structures are derived from an ancient, common ancestor and is in sharp contrast to the lack of such evidence for other virus functions. Copyright © 2014. Published by Elsevier B.V.

  8. Structural similarity image quality reliability: Determining parameters and window size

    OpenAIRE

    Silvestre-Blanes, Javier

    2011-01-01

    The need to obtain objective values of the quality of distorted images with respect to the original is fundamental in multimedia and image processing applications. It is generally required that this value correlates well with the human vision system (HVS). In spite of the properties and the general use of the mean square error (MSE) measurement, this has a poor correlation with HSV, which has led to the development of methods such as structural similarity (SSIM). This metric improves the corr...

  9. Investigation of Time Series Representations and Similarity Measures for Structural Damage Pattern Recognition

    Science.gov (United States)

    Swartz, R. Andrew

    2013-01-01

    This paper investigates the time series representation methods and similarity measures for sensor data feature extraction and structural damage pattern recognition. Both model-based time series representation and dimensionality reduction methods are studied to compare the effectiveness of feature extraction for damage pattern recognition. The evaluation of feature extraction methods is performed by examining the separation of feature vectors among different damage patterns and the pattern recognition success rate. In addition, the impact of similarity measures on the pattern recognition success rate and the metrics for damage localization are also investigated. The test data used in this study are from the System Identification to Monitor Civil Engineering Structures (SIMCES) Z24 Bridge damage detection tests, a rigorous instrumentation campaign that recorded the dynamic performance of a concrete box-girder bridge under progressively increasing damage scenarios. A number of progressive damage test case datasets and damage test data with different damage modalities are used. The simulation results show that both time series representation methods and similarity measures have significant impact on the pattern recognition success rate. PMID:24191136

  10. Investigation of Time Series Representations and Similarity Measures for Structural Damage Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Wenjia Liu

    2013-01-01

    Full Text Available This paper investigates the time series representation methods and similarity measures for sensor data feature extraction and structural damage pattern recognition. Both model-based time series representation and dimensionality reduction methods are studied to compare the effectiveness of feature extraction for damage pattern recognition. The evaluation of feature extraction methods is performed by examining the separation of feature vectors among different damage patterns and the pattern recognition success rate. In addition, the impact of similarity measures on the pattern recognition success rate and the metrics for damage localization are also investigated. The test data used in this study are from the System Identification to Monitor Civil Engineering Structures (SIMCES Z24 Bridge damage detection tests, a rigorous instrumentation campaign that recorded the dynamic performance of a concrete box-girder bridge under progressively increasing damage scenarios. A number of progressive damage test case datasets and damage test data with different damage modalities are used. The simulation results show that both time series representation methods and similarity measures have significant impact on the pattern recognition success rate.

  11. Bioengineering of rFVIIa Biopharmaceutical and Structure Characterization for Biosimilarity Assessment

    Directory of Open Access Journals (Sweden)

    Othman Montacir

    2018-01-01

    Full Text Available Eptacog alfa (NovoSeven® is a vitamin K-dependent recombinant Factor VIIa produced by genetic engineering from baby hamster kidney (BHK cells as a single peptide chain of 406 residues. After activation, it consists of a light chain (LC of 152 amino and a heavy chain (HC of 254 amino acids. Recombinant FVIIa undergoes many post-translational modifications (PTMs. The first ten glutamic acids of the N-terminal moiety are γ-carboxylated, Asn145 and Asn322 are N-glycosylated, and Ser52 and Ser60 are O-glycosylated. A head-to-head biosimilarity study was conducted for the originator and the first biosimilar AryoSeven™ to evaluate comparable bioengineering. Physicochemical properties were analyzed based on mass spectrometry, including intact mass, PTMs and higher-order structure. Both biotherapeutics exhibit a batch-to-batch variability in their N-glycan profiles. N-Glycopeptide analysis with UHPLC-QTOF-MSE confirmed N-glycosylation sites as well as two different O-glycopeptide sites. Ser60 was found to be O-fucosylated and Ser52 had O-glucose or O-glucose-(xylose1,2 motifs as glycan variants. Ion mobility spectrometry (TWIMS and NMR spectroscopy data affirm close similarity of the higher-order structure of both biologicals. Potency of the biodrugs was analyzed by a coagulation assay demonstrating comparable bioactivity. Consequently, careful process optimization led to a stable production process of the biopharmaceuticals.

  12. Searching the protein structure database for ligand-binding site similarities using CPASS v.2

    Directory of Open Access Journals (Sweden)

    Caprez Adam

    2011-01-01

    Full Text Available Abstract Background A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2 database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function. Findings We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated. Conclusions CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores

  13. Monitoring engineering structures by the comparison of similar photographs

    International Nuclear Information System (INIS)

    Jones, A.

    1976-12-01

    A commonly used method of monitoring engineering structures is to compare similar photographs taken at different times. The initial part of this note deals with commercially available equipment, known as a comparascope, which enables differences between photographs to be rapidly (and reliably) detected. A series of practical tests is described in which it is established that a change in dimensions of 0.05mm can be detected between photographs. For typical camera systems, this will usually correspond to detectable displacements of the order of several mm in object space. Perhaps the most serious disadvantages of the technique is that alterations in camera attitude between photographs can cause changes in the recorded image which mask genuine movements in the structure. The changes caused by a given shift in camera attitude are, therefore, investigated theoretically. Since it is desirable that the changes are small enough to go undetected in the comparison, the established detection limit of the comparascope is included in the investigation to specify how accurately the camera attitude must be controlled for a given set of experimental circumstances. As a result, it appears that a special purpose camera mounting will nearly always be required if structural differences as small as several mm are to be reliably detected. Hand-held cameras should only be used for relatively coarse monitoring tasks. (author)

  14. Structural similarities between brain and linguistic data provide evidence of semantic relations in the brain.

    Directory of Open Access Journals (Sweden)

    Colleen E Crangle

    Full Text Available This paper presents a new method of analysis by which structural similarities between brain data and linguistic data can be assessed at the semantic level. It shows how to measure the strength of these structural similarities and so determine the relatively better fit of the brain data with one semantic model over another. The first model is derived from WordNet, a lexical database of English compiled by language experts. The second is given by the corpus-based statistical technique of latent semantic analysis (LSA, which detects relations between words that are latent or hidden in text. The brain data are drawn from experiments in which statements about the geography of Europe were presented auditorily to participants who were asked to determine their truth or falsity while electroencephalographic (EEG recordings were made. The theoretical framework for the analysis of the brain and semantic data derives from axiomatizations of theories such as the theory of differences in utility preference. Using brain-data samples from individual trials time-locked to the presentation of each word, ordinal relations of similarity differences are computed for the brain data and for the linguistic data. In each case those relations that are invariant with respect to the brain and linguistic data, and are correlated with sufficient statistical strength, amount to structural similarities between the brain and linguistic data. Results show that many more statistically significant structural similarities can be found between the brain data and the WordNet-derived data than the LSA-derived data. The work reported here is placed within the context of other recent studies of semantics and the brain. The main contribution of this paper is the new method it presents for the study of semantics and the brain and the focus it permits on networks of relations detected in brain data and represented by a semantic model.

  15. Molecular similarity measures.

    Science.gov (United States)

    Maggiora, Gerald M; Shanmugasundaram, Veerabahu

    2011-01-01

    Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

  16. Similarity or difference?

    DEFF Research Database (Denmark)

    Villadsen, Anders Ryom

    2013-01-01

    While the organizational structures and strategies of public organizations have attracted substantial research attention among public management scholars, little research has explored how these organizational core dimensions are interconnected and influenced by pressures for similarity....... In this paper I address this topic by exploring the relation between expenditure strategy isomorphism and structure isomorphism in Danish municipalities. Different literatures suggest that organizations exist in concurrent pressures for being similar to and different from other organizations in their field......-shaped relation exists between expenditure strategy isomorphism and structure isomorphism in a longitudinal quantitative study of Danish municipalities....

  17. Towards a chromatographic similarity index to establish localised quantitative structure-retention relationships for retention prediction. II Use of Tanimoto similarity index in ion chromatography.

    Science.gov (United States)

    Park, Soo Hyun; Talebi, Mohammad; Amos, Ruth I J; Tyteca, Eva; Haddad, Paul R; Szucs, Roman; Pohl, Christopher A; Dolan, John W

    2017-11-10

    Quantitative Structure-Retention Relationships (QSRR) are used to predict retention times of compounds based only on their chemical structures encoded by molecular descriptors. The main concern in QSRR modelling is to build models with high predictive power, allowing reliable retention prediction for the unknown compounds across the chromatographic space. With the aim of enhancing the prediction power of the models, in this work, our previously proposed QSRR modelling approach called "federation of local models" is extended in ion chromatography to predict retention times of unknown ions, where a local model for each target ion (unknown) is created using only structurally similar ions from the dataset. A Tanimoto similarity (TS) score was utilised as a measure of structural similarity and training sets were developed by including ions that were similar to the target ion, as defined by a threshold value. The prediction of retention parameters (a- and b-values) in the linear solvent strength (LSS) model in ion chromatography, log k=a - blog[eluent], allows the prediction of retention times under all eluent concentrations. The QSRR models for a- and b-values were developed by a genetic algorithm-partial least squares method using the retention data of inorganic and small organic anions and larger organic cations (molecular mass up to 507) on four Thermo Fisher Scientific columns (AS20, AS19, AS11HC and CS17). The corresponding predicted retention times were calculated by fitting the predicted a- and b-values of the models into the LSS model equation. The predicted retention times were also plotted against the experimental values to evaluate the goodness of fit and the predictive power of the models. The application of a TS threshold of 0.6 was found to successfully produce predictive and reliable QSRR models (Q ext(F2) 2 >0.8 and Mean Absolute Error<0.1), and hence accurate retention time predictions with an average Mean Absolute Error of 0.2min. Crown Copyright

  18. Structural similarities and differences between the human and the mouse pancreas

    Science.gov (United States)

    Dolenšek, Jurij; Rupnik, Marjan Slak; Stožer, Andraž

    2015-01-01

    Mice remain the most studied animal model in pancreas research. Since the findings of this research are typically extrapolated to humans, it is important to understand both similarities and differences between the 2 species. Beside the apparent difference in size and macroscopic organization of the organ in the 2 species, there are a number of less evident and only recently described differences in organization of the acinar and ductal exocrine tissue, as well as in the distribution, composition, and architecture of the endocrine islets of Langerhans. Furthermore, the differences in arterial, venous, and lymphatic vessels, as well as innervation are potentially important. In this article, the structure of the human and the mouse pancreas, together with the similarities and differences between them are reviewed in detail in the light of conceivable repercussions for basic research and clinical application. PMID:26030186

  19. Internal structures of self-organized relaxed states and self-similar decay phase

    International Nuclear Information System (INIS)

    Kondoh, Yoshiomi

    1992-03-01

    A thought analysis on relaxation due to nonlinear processes is presented to lead to a set of general thoughts applicable to general nonlinear dynamical systems for finding out internal structures of the self-organized relaxed state without using 'invariant'. Three applications of the set of general thoughts to energy relaxations in resistive MHD plasmas, incompressible viscous fluids, and incompressible viscous MHD fluids are shown to lead to the internal structures of the self-organized relaxed states. It is shown that all of the relaxed states in these three dynamical systems are followed by self-similar decay phase without significant change of the spatial structure. The well known relaxed state of ∇ x B = ±λ B is shown to be derived generally in the low β plasma limit. (author)

  20. Neighborhood Structural Similarity Mapping for the Classification of Masses in Mammograms.

    Science.gov (United States)

    Rabidas, Rinku; Midya, Abhishek; Chakraborty, Jayasree

    2018-05-01

    In this paper, two novel feature extraction methods, using neighborhood structural similarity (NSS), are proposed for the characterization of mammographic masses as benign or malignant. Since gray-level distribution of pixels is different in benign and malignant masses, more regular and homogeneous patterns are visible in benign masses compared to malignant masses; the proposed method exploits the similarity between neighboring regions of masses by designing two new features, namely, NSS-I and NSS-II, which capture global similarity at different scales. Complementary to these global features, uniform local binary patterns are computed to enhance the classification efficiency by combining with the proposed features. The performance of the features are evaluated using the images from the mini-mammographic image analysis society (mini-MIAS) and digital database for screening mammography (DDSM) databases, where a tenfold cross-validation technique is incorporated with Fisher linear discriminant analysis, after selecting the optimal set of features using stepwise logistic regression method. The best area under the receiver operating characteristic curve of 0.98 with an accuracy of is achieved with the mini-MIAS database, while the same for the DDSM database is 0.93 with accuracy .

  1. Comparative analysis of chemical similarity methods for modular natural products with a hypothetical structure enumeration algorithm.

    Science.gov (United States)

    Skinnider, Michael A; Dejong, Chris A; Franczak, Brian C; McNicholas, Paul D; Magarvey, Nathan A

    2017-08-16

    Natural products represent a prominent source of pharmaceutically and industrially important agents. Calculating the chemical similarity of two molecules is a central task in cheminformatics, with applications at multiple stages of the drug discovery pipeline. Quantifying the similarity of natural products is a particularly important problem, as the biological activities of these molecules have been extensively optimized by natural selection. The large and structurally complex scaffolds of natural products distinguish their physical and chemical properties from those of synthetic compounds. However, no analysis of the performance of existing methods for molecular similarity calculation specific to natural products has been reported to date. Here, we present LEMONS, an algorithm for the enumeration of hypothetical modular natural product structures. We leverage this algorithm to conduct a comparative analysis of molecular similarity methods within the unique chemical space occupied by modular natural products using controlled synthetic data, and comprehensively investigate the impact of diverse biosynthetic parameters on similarity search. We additionally investigate a recently described algorithm for natural product retrobiosynthesis and alignment, and find that when rule-based retrobiosynthesis can be applied, this approach outperforms conventional two-dimensional fingerprints, suggesting it may represent a valuable approach for the targeted exploration of natural product chemical space and microbial genome mining. Our open-source algorithm is an extensible method of enumerating hypothetical natural product structures with diverse potential applications in bioinformatics.

  2. Wind loads and competition for light sculpt trees into self-similar structures.

    Science.gov (United States)

    Eloy, Christophe; Fournier, Meriem; Lacointe, André; Moulia, Bruno

    2017-10-18

    Trees are self-similar structures: their branch lengths and diameters vary allometrically within the tree architecture, with longer and thicker branches near the ground. These tree allometries are often attributed to optimisation of hydraulic sap transport and safety against elastic buckling. Here, we show that these allometries also emerge from a model that includes competition for light, wind biomechanics and no hydraulics. We have developed MECHATREE, a numerical model of trees growing and evolving on a virtual island. With this model, we identify the fittest growth strategy when trees compete for light and allocate their photosynthates to grow seeds, create new branches or reinforce existing ones in response to wind-induced loads. Strikingly, we find that selected trees species are self-similar and follow allometric scalings similar to those observed on dicots and conifers. This result suggests that resistance to wind and competition for light play an essential role in determining tree allometries.

  3. A discriminative structural similarity measure and its application to video-volume registration for endoscope three-dimensional motion tracking.

    Science.gov (United States)

    Luo, Xiongbiao; Mori, Kensaku

    2014-06-01

    Endoscope 3-D motion tracking, which seeks to synchronize pre- and intra-operative images in endoscopic interventions, is usually performed as video-volume registration that optimizes the similarity between endoscopic video and pre-operative images. The tracking performance, in turn, depends significantly on whether a similarity measure can successfully characterize the difference between video sequences and volume rendering images driven by pre-operative images. The paper proposes a discriminative structural similarity measure, which uses the degradation of structural information and takes image correlation or structure, luminance, and contrast into consideration, to boost video-volume registration. By applying the proposed similarity measure to endoscope tracking, it was demonstrated to be more accurate and robust than several available similarity measures, e.g., local normalized cross correlation, normalized mutual information, modified mean square error, or normalized sum squared difference. Based on clinical data evaluation, the tracking error was reduced significantly from at least 14.6 mm to 4.5 mm. The processing time was accelerated more than 30 frames per second using graphics processing unit.

  4. Prediction of Protein Structural Classes for Low-Similarity Sequences Based on Consensus Sequence and Segmented PSSM

    Directory of Open Access Journals (Sweden)

    Yunyun Liang

    2015-01-01

    Full Text Available Prediction of protein structural classes for low-similarity sequences is useful for understanding fold patterns, regulation, functions, and interactions of proteins. It is well known that feature extraction is significant to prediction of protein structural class and it mainly uses protein primary sequence, predicted secondary structure sequence, and position-specific scoring matrix (PSSM. Currently, prediction solely based on the PSSM has played a key role in improving the prediction accuracy. In this paper, we propose a novel method called CSP-SegPseP-SegACP by fusing consensus sequence (CS, segmented PsePSSM, and segmented autocovariance transformation (ACT based on PSSM. Three widely used low-similarity datasets (1189, 25PDB, and 640 are adopted in this paper. Then a 700-dimensional (700D feature vector is constructed and the dimension is decreased to 224D by using principal component analysis (PCA. To verify the performance of our method, rigorous jackknife cross-validation tests are performed on 1189, 25PDB, and 640 datasets. Comparison of our results with the existing PSSM-based methods demonstrates that our method achieves the favorable and competitive performance. This will offer an important complementary to other PSSM-based methods for prediction of protein structural classes for low-similarity sequences.

  5. Pairwise local structural alignment of RNA sequences with sequence similarity less than 40%

    DEFF Research Database (Denmark)

    Havgaard, Jakob Hull; Lyngsø, Rune B.; Stormo, Gary D.

    2005-01-01

    detect two genes with low sequence similarity, where the genes are part of a larger genomic region. Results: Here we present such an approach for pairwise local alignment which is based on FILDALIGN and the Sankoff algorithm for simultaneous structural alignment of multiple sequences. We include...... the ability to conduct mutual scans of two sequences of arbitrary length while searching for common local structural motifs of some maximum length. This drastically reduces the complexity of the algorithm. The scoring scheme includes structural parameters corresponding to those available for free energy....... The structure prediction performance for a family is typically around 0.7 using Matthews correlation coefficient. In case (2), the algorithm is successful at locating RNA families with an average sensitivity of 0.8 and a positive predictive value of 0.9 using a BLAST-like hit selection scheme. Availability...

  6. Similarity between community structures of different online social networks and its impact on underlying community detection

    Science.gov (United States)

    Fan, W.; Yeung, K. H.

    2015-03-01

    As social networking services are popular, many people may register in more than one online social network. In this paper we study a set of users who have accounts of three online social networks: namely Foursquare, Facebook and Twitter. Community structure of this set of users may be reflected in these three online social networks. Therefore, high correlation between these reflections and the underlying community structure may be observed. In this work, community structures are detected in all three online social networks. Also, we investigate the similarity level of community structures across different networks. It is found that they show strong correlation with each other. The similarity between different networks may be helpful to find a community structure close to the underlying one. To verify this, we propose a method to increase the weights of some connections in networks. With this method, new networks are generated to assist community detection. By doing this, value of modularity can be improved and the new community structure match network's natural structure better. In this paper we also show that the detected community structures of online social networks are correlated with users' locations which are identified on Foursquare. This information may also be useful for underlying community detection.

  7. Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure.

    Science.gov (United States)

    Strasser, Richard; Stadlmann, Johannes; Schähs, Matthias; Stiegler, Gabriela; Quendler, Heribert; Mach, Lukas; Glössl, Josef; Weterings, Koen; Pabst, Martin; Steinkellner, Herta

    2008-05-01

    A common argument against using plants as a production system for therapeutic proteins is their inability to perform authentic human N-glycosylation (i.e. the presence of beta1,2-xylosylation and core alpha1,3-fucosylation). In this study, RNA interference (RNAi) technology was used to obtain a targeted down-regulation of the endogenous beta1,2-xylosyltransferase (XylT) and alpha1,3-fucosyltransferase (FucT) genes in Nicotiana benthamiana, a tobacco-related plant species widely used for recombinant protein expression. Three glyco-engineered lines with significantly reduced xylosylated and/or core alpha1,3-fucosylated glycan structures were generated. The human anti HIV monoclonal antibody 2G12 was transiently expressed in these glycosylation mutants as well as in wild-type plants. Four glycoforms of 2G12 differing in the presence/absence of xylose and core alpha1,3-fucose residues in their N-glycans were produced. Notably, 2G12 produced in XylT/FucT-RNAi plants was found to contain an almost homogeneous N-glycan species without detectable xylose and alpha1,3-fucose residues. Plant-derived glycoforms were indistinguishable from Chinese hamster ovary (CHO)-derived 2G12 with respect to electrophoretic properties, and exhibited functional properties (i.e. antigen binding and HIV neutralization activity) at least equivalent to those of the CHO counterpart. The generated RNAi lines were stable, viable and did not show any obvious phenotype, thus providing a robust tool for the production of therapeutically relevant glycoproteins in plants with a humanized N-glycan structure.

  8. Neutral N-glycan patterns of the gastropods Limax maximus, Cepaea hortensis, Planorbarius corneus, Arianta arbustorum and Achatina fulica.

    Science.gov (United States)

    Gutternigg, Martin; Bürgmayr, Sabine; Pöltl, Gerald; Rudolf, Judith; Staudacher, Erika

    2007-11-01

    The N-glycosylation potentials of Limax maximus, Cepaea hortensis, Planorbarius corneus, Arianta arbustorum and Achatina fulica were analysed by investigation of the N-glycan structures of the skin and viscera glycoproteins by a combination of HPLC and mass-spectrometry methods. It is one of the first steps to enlarge the knowledge on the glycosylation abilities of gastropods, which may help to establish new cell culture systems, to uncover new means for pest control for some species, and to identify carbohydrate-epitopes which may be relevant for immune response. All snails analysed contained mainly oligomannosidic and small paucimannosidic structures, often terminated with 3-O-methylated mannoses. The truncated structures carried modifications by beta1-2-linked xylose to the beta-mannose residue, and/or an alpha-fucosylation, mainly alpha1,6-linked to the innermost N-acetylglucosaminyl residue of the core. Many of these structures were missing the terminal N-acetylglucosamine, which has been shown to be a prerequisite for processing to complex N-glycans in the Golgi. In some species (Planorbarius corneus and Achatina fulica) traces of large structures, terminated by 3-O-methylated galactoses and carrying xylose and/or fucose residues, were also detected. In Planorbarius viscera low amounts of terminal alpha1-2-fucosylation were determined. Combining these results, gastropods seem to be capable to produce all kinds of structures ranging from those typical in mammals through to structures similar to those found in plants, insects or nematodes. The detailed knowledge of this very complex glycosylation system of the gastropods will be a valuable tool to understand the principle rules of glycosylation in all organisms.

  9. Macrophage and NK-mediated killing of precursor-B acute lymphoblastic leukemia cells targeted with a-fucosylated anti-CD19 humanized antibodies.

    Science.gov (United States)

    Matlawska-Wasowska, K; Ward, E; Stevens, S; Wang, Y; Herbst, R; Winter, S S; Wilson, B S

    2013-06-01

    This work reports the tumoricidal effects of a novel investigational humanized anti-CD19 monoclonal antibody (Medi-551). An a-fucosylated antibody with increased affinity for human FcγRIIIA, Medi-551 is shown to mediate both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Medi-551/CD19 complexes internalize slowly (>5 h) and thus remain accessible to effector cells for prolonged periods. We evaluated in vitro ADCC and ADCP activities of primary human natural killer (NK) cells and macrophages against precursor-B (pre-B) acute lymphoblastic leukemia (ALL) cell lines and pediatric patient blasts. Fluorescent imaging studies document immunological synapses formed between anti-CD19-bound target leukemia cells and effector cells and capture the kinetics of both NK-mediated killing and macrophage phagocytosis. Genetic polymorphisms in FcγRIIIA-158F/V modulate in vitro activities of effector cells, with FcγRIIIA-158V homozygotes or heterozygotes showing the strongest activity. Medi-551 treatment of severe combined immunodeficiency (SCID) mice engrafted with human pre-B cells led to prolonged animal survival and markedly reduced disease burden in blood, liver and bone marrow. These data show that anti-CD19 antibodies effectively recruit immune cells to pre-B ALL cells and support a move forward to early phase trials in this disease.

  10. Volutin granules of Eimeria parasites are acidic compartments and have physiological and structural characteristics similar to acidocalcisomes

    Science.gov (United States)

    Medeiros, Lia Carolina Soares; Gomes, Fabio; Maciel, Luis Renato Maia; Seabra, Sergio Henrique; Docampo, Roberto; Moreno, Silvia; Plattner, Helmut; Hentschel, Joachim; Kawazoe, Urara; Barrabin, Hector; de Souza, Wanderley; DaMatta, Renato Augusto; Miranda, Kildare

    2012-01-01

    The structural organization of parasites has been the subject of investigation by many groups and has lead to the identification of structures and metabolic pathways that may represent targets for anti-parasitic drugs. A specific group of organelles named acidocalcisomes has been identified in a number of organisms, including the apicomplexan parasites such as Toxoplasma and Plasmodium, where they have been shown to be involved in cation homeostasis, polyphosphate metabolism, and osmoregulation. Their structural counterparts in the apicomplexan parasite Eimeria have not been fully characterized. In this work, the ultrastructural and chemical properties of acidocalcisomes in Eimeria were characterized. Electron microscopy analysis of Eimeria parasites showed the dense organelles called volutin granules similar to acidocalcisomes. Immunolocalization of the vacuolar proton pyrophosphatase, considered as a marker for acidocalcisomes, showed labeling in vesicles of size and distribution similar to the dense organelles seen by electron microscopy. Spectrophotometric measurements of the kinetics of proton uptake showed a vacuolar proton pyrophosphatase activity. X-ray mapping revealed significant amounts of Na, Mg, P, K, Ca, and Zn in their matrix. The results suggest that volutin granules of Eimeria parasites are acidic, dense organelles and possess structural and chemical properties analogous to those of other acidocalcisomes, suggesting a similar functional role in these parasites. PMID:21699625

  11. Common neighbour structure and similarity intensity in complex networks

    Science.gov (United States)

    Hou, Lei; Liu, Kecheng

    2017-10-01

    Complex systems as networks always exhibit strong regularities, implying underlying mechanisms governing their evolution. In addition to the degree preference, the similarity has been argued to be another driver for networks. Assuming a network is randomly organised without similarity preference, the present paper studies the expected number of common neighbours between vertices. A symmetrical similarity index is accordingly developed by removing such expected number from the observed common neighbours. The developed index can not only describe the similarities between vertices, but also the dissimilarities. We further apply the proposed index to measure of the influence of similarity on the wring patterns of networks. Fifteen empirical networks as well as artificial networks are examined in terms of similarity intensity and degree heterogeneity. Results on real networks indicate that, social networks are strongly governed by the similarity as well as the degree preference, while the biological networks and infrastructure networks show no apparent similarity governance. Particularly, classical network models, such as the Barabási-Albert model, the Erdös-Rényi model and the Ring Lattice, cannot well describe the social networks in terms of the degree heterogeneity and similarity intensity. The findings may shed some light on the modelling and link prediction of different classes of networks.

  12. Improvement of training set structure in fusion data cleaning using Time-Domain Global Similarity method

    International Nuclear Information System (INIS)

    Liu, J.; Lan, T.; Qin, H.

    2017-01-01

    Traditional data cleaning identifies dirty data by classifying original data sequences, which is a class-imbalanced problem since the proportion of incorrect data is much less than the proportion of correct ones for most diagnostic systems in Magnetic Confinement Fusion (MCF) devices. When using machine learning algorithms to classify diagnostic data based on class-imbalanced training set, most classifiers are biased towards the major class and show very poor classification rates on the minor class. By transforming the direct classification problem about original data sequences into a classification problem about the physical similarity between data sequences, the class-balanced effect of Time-Domain Global Similarity (TDGS) method on training set structure is investigated in this paper. Meanwhile, the impact of improved training set structure on data cleaning performance of TDGS method is demonstrated with an application example in EAST POlarimetry-INTerferometry (POINT) system.

  13. MetalS(3), a database-mining tool for the identification of structurally similar metal sites.

    Science.gov (United States)

    Valasatava, Yana; Rosato, Antonio; Cavallaro, Gabriele; Andreini, Claudia

    2014-08-01

    We have developed a database search tool to identify metal sites having structural similarity to a query metal site structure within the MetalPDB database of minimal functional sites (MFSs) contained in metal-binding biological macromolecules. MFSs describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such a local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. The database search tool, which we called MetalS(3) (Metal Sites Similarity Search), can be accessed through a Web interface at http://metalweb.cerm.unifi.it/tools/metals3/ . MetalS(3) uses a suitably adapted version of an algorithm that we previously developed to systematically compare the structure of the query metal site with each MFS in MetalPDB. For each MFS, the best superposition is kept. All these superpositions are then ranked according to the MetalS(3) scoring function and are presented to the user in tabular form. The user can interact with the output Web page to visualize the structural alignment or the sequence alignment derived from it. Options to filter the results are available. Test calculations show that the MetalS(3) output correlates well with expectations from protein homology considerations. Furthermore, we describe some usage scenarios that highlight the usefulness of MetalS(3) to obtain mechanistic and functional hints regardless of homology.

  14. Development of scaffold-free elastic cartilaginous constructs with structural similarities to auricular cartilage.

    Science.gov (United States)

    Giardini-Rosa, Renata; Joazeiro, Paulo P; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna; Waldman, Stephen D

    2014-03-01

    External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternatively, tissue engineering can offer the potential to grow autogenous cartilage suitable for implantation. While tissue-engineered auricle cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for reconstruction. Similarly, as routine cell expansion can elicit negative effects on chondrocyte function, we have developed an approach to generate large-sized engineered auricle constructs (≥3 cm(2)) directly from a small population of donor cells (20,000-40,000 cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated constructs adopted structural-like characteristics similar to native auricular cartilage, including the development of distinct cartilaginous and perichondrium-like regions. Both alterations in media composition and seeding density had profound effects on the formation of engineered elastic tissue constructs in terms of cellularity, extracellular matrix accumulation, and tissue structure. Higher seeding densities and media containing sodium bicarbonate produced tissue constructs that were closer to the native tissue in terms of structure and composition. Future studies will be aimed at improving the accumulation of specific tissue constituents and determining the clinical effectiveness of this approach using a reconstructive animal model.

  15. Genomics meets glycomics-the first GWAS study of human N-Glycome identifies HNF1α as a master regulator of plasma protein fucosylation.

    Directory of Open Access Journals (Sweden)

    Gordan Lauc

    2010-12-01

    Full Text Available Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate their assembly are poorly understood. A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1α and its downstream target HNF4α regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1α is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1α as a master transcriptional regulator of multiple stages in the fucosylation process. This mechanism has implications for the regulation of immunity, embryonic development, and protein folding, as well as for our understanding of the molecular mechanisms underlying cancer, coronary heart disease, and metabolic and inflammatory disorders.

  16. Site-specific glycosylation of donkey milk lactoferrin investigated by high-resolution mass spectrometry

    DEFF Research Database (Denmark)

    Gallina, Serafina; Saletti, Rosaria; Cunsolo, Vincenzo

    2016-01-01

    A comprehensive monosaccharide composition of the N-glycans of donkey milk lactoferrin, isolated by ion exchange chromatography from an individual milk sample, was obtained by means of chymotryptic digestion, TiO2 and HILIC enrichment, reversed-phase high-performance liquid chromatography......, electrospray mass spectrometry, and high collision dissociation fragmentation. The results obtained allowed identifying 26 different glycan structures, including high mannose, complex and hybrid N-glycans, linked to the protein backbone via an amide bond to asparagine residues located at the positions 137, 281...... and 476. Altogether, the N-glycan structures determined revealed that most of the N-glycans identified in donkey milk lactoferrin are neutral complex/hybrid. Indeed, 10 neutral non-fucosylated complex/hybrid N-glycans and 4 neutral fucosylated complex/hybrid N-glycans were found. In addition, two high...

  17. Processes of Similarity Judgment

    Science.gov (United States)

    Larkey, Levi B.; Markman, Arthur B.

    2005-01-01

    Similarity underlies fundamental cognitive capabilities such as memory, categorization, decision making, problem solving, and reasoning. Although recent approaches to similarity appreciate the structure of mental representations, they differ in the processes posited to operate over these representations. We present an experiment that…

  18. Wake structure and similar behavior of wake profiles downstream of a plunging airfoil

    Directory of Open Access Journals (Sweden)

    Ali R. DAVARI

    2017-08-01

    Full Text Available Very limited attention has already been paid to the velocity behavior in the wake region in unsteady aerodynamic problems. A series of tests has been performed on a flapping airfoil in a subsonic wind tunnel to study the wake structure for different sets of mean angle of attack, plunging amplitude and reduced frequency. In this study, the velocity profiles in the wake for various oscillation parameters have been measured using a wide shoulder rake, especially designed for the present experiments. The airfoil under consideration was a critical section of a 660 kW wind turbine. The results show that for a flapping airfoil the wake structure can be of drag producing type, thrust producing or neutral, depending on the mean angle of attack, oscillation amplitude and reduced frequency. In a thrust producing wake, a high-momentum high-velocity jet flow is formed in the core region of the wake instead of the conventional low-momentum flow. As a result, the drag force normally experienced by the body due to the momentum deficit would be replaced by a thrust force. According to the results, the momentum loss in the wake decreases as the reduced frequency increases. The thrust producing wake pattern for the flapping airfoil has been observed for sufficiently low angles of attack in the absence of the viscous effects. This phenomenon has also been observed for either high oscillation amplitudes or high reduced frequencies. According to the results, for different reduced frequencies and plunging amplitudes, such that the product of them be a constant, the velocity profiles exhibit similar behavior and coalesce on each other. This similarity parameter works excellently at small angles of attack. However, at near stall boundaries, the similarity is not as evident as before.

  19. Earthworm coelomocyte extracellular traps: structural and functional similarities with neutrophil NETs.

    Science.gov (United States)

    Homa, Joanna

    2018-03-01

    Invertebrate immunity is associated with natural mechanisms that include cellular and humoral elements, similar to those that play a role in vertebrate innate immune responses. Formation of extracellular traps (ETs) is a newly discovered mechanism to combat pathogens, operating not only in vertebrate leucocytes but also in invertebrate immune cells. The ET components include extracellular DNA (exDNA), antimicrobial proteins and histones. Formation of mammalian ETs depends on enzymes such as neutrophil elastase, myeloperoxidase, the citrullination of histones and protease activity. It was confirmed that coelomocytes-immunocompetent cells of the earthworm Eisenia andrei-are also able to release ETs in a protease-dependent manner, dependent or independent of the formation of reactive oxygen species and rearrangement of the cell cytoskeleton. Similar to vertebrate leukocytes (e.g., neutrophil), coelomocytes are responsible for many immune functions like phagocytosis, cytotoxicity and secretion of humoral factors. ETs formed by coelomocyte analogues to neutrophil ETs consist of exDNA, histone H3 and attached to these structures proteins, e.g., heat shock proteins HSP27. The latter fact confirms that mechanisms of ET release are conserved in evolution. The study on Annelida adds this animal group to the list of invertebrates capable of ET release, but most importantly provides insides into innate mechanisms of ET formation in lower animal taxa.

  20. RxnFinder: biochemical reaction search engines using molecular structures, molecular fragments and reaction similarity.

    Science.gov (United States)

    Hu, Qian-Nan; Deng, Zhe; Hu, Huanan; Cao, Dong-Sheng; Liang, Yi-Zeng

    2011-09-01

    Biochemical reactions play a key role to help sustain life and allow cells to grow. RxnFinder was developed to search biochemical reactions from KEGG reaction database using three search criteria: molecular structures, molecular fragments and reaction similarity. RxnFinder is helpful to get reference reactions for biosynthesis and xenobiotics metabolism. RxnFinder is freely available via: http://sdd.whu.edu.cn/rxnfinder. qnhu@whu.edu.cn.

  1. StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Zemla, A; Lang, D; Kostova, T; Andino, R; Zhou, C

    2010-11-29

    Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory - still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could overcome these difficulties and facilitate the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV, a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus and demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique or that shared structural similarity with structures that are distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected

  2. On universal common ancestry, sequence similarity, and phylogenetic structure: the sins of P-values and the virtues of Bayesian evidence

    Directory of Open Access Journals (Sweden)

    Theobald Douglas L

    2011-11-01

    Full Text Available Abstract Background The universal common ancestry (UCA of all known life is a fundamental component of modern evolutionary theory, supported by a wide range of qualitative molecular evidence. Nevertheless, recently both the status and nature of UCA has been questioned. In earlier work I presented a formal, quantitative test of UCA in which model selection criteria overwhelmingly choose common ancestry over independent ancestry, based on a dataset of universally conserved proteins. These model-based tests are founded in likelihoodist and Bayesian probability theory, in opposition to classical frequentist null hypothesis tests such as Karlin-Altschul E-values for sequence similarity. In a recent comment, Koonin and Wolf (K&W claim that the model preference for UCA is "a trivial consequence of significant sequence similarity". They support this claim with a computational simulation, derived from universally conserved proteins, which produces similar sequences lacking phylogenetic structure. The model selection tests prefer common ancestry for this artificial data set. Results For the real universal protein sequences, hierarchical phylogenetic structure (induced by genealogical history is the overriding reason for why the tests choose UCA; sequence similarity is a relatively minor factor. First, for cases of conflicting phylogenetic structure, the tests choose independent ancestry even with highly similar sequences. Second, certain models, like star trees and K&W's profile model (corresponding to their simulation, readily explain sequence similarity yet lack phylogenetic structure. However, these are extremely poor models for the real proteins, even worse than independent ancestry models, though they explain K&W's artificial data well. Finally, K&W's simulation is an implementation of a well-known phylogenetic model, and it produces sequences that mimic homologous proteins. Therefore the model selection tests work appropriately with the artificial

  3. Structural similarity between β(3)-peptides synthesized from β(3)-homo-amino acids and aspartic acid monomers.

    Science.gov (United States)

    Ahmed, Sahar; Sprules, Tara; Kaur, Kamaljit

    2014-07-01

    Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β(3)-hexapeptides synthesized from L-aspartic acid monomers (β(3)-peptides 1, 5a, and 6) or homologated β(3)-amino acids (β(3)-peptide 2), fold into similar stable 14-helical secondary structures in solution, except that the former form right-handed 14-helix and the later form left-handed 14-helix. β(3)-Peptides from L-Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the NMR solution structures, we found that β(3)-peptide from L-Asp monomers (1) and from homologated amino acids (2) form similar structures with no additional side-chain interactions. These results suggest that the β(3)-peptides derived from L-Asp are promising peptide-mimetics that can be readily synthesized using L-Asp monomers as well as the right-handed 14-helical conformation of these β(3)-peptides (such as 1 and 6) may prove beneficial in the design of mimics for right-handed α-helix of α-peptides. © 2014 Wiley Periodicals, Inc.

  4. UPF201 Archaeal Specific Family Members Reveals Structural Similarity to RNA-Binding Proteins but Low Likelihood for RNA-Binding Function

    Energy Technology Data Exchange (ETDEWEB)

    Rao, K.N.; Swaminathan, S.; Burley, S. K.

    2008-12-11

    We have determined X-ray crystal structures of four members of an archaeal specific family of proteins of unknown function (UPF0201; Pfam classification: DUF54) to advance our understanding of the genetic repertoire of archaea. Despite low pairwise amino acid sequence identities (10-40%) and the absence of conserved sequence motifs, the three-dimensional structures of these proteins are remarkably similar to one another. Their common polypeptide chain fold, encompassing a five-stranded antiparallel {beta}-sheet and five {alpha}-helices, proved to be quite unexpectedly similar to that of the RRM-type RNA-binding domain of the ribosomal L5 protein, which is responsible for binding the 5S- rRNA. Structure-based sequence alignments enabled construction of a phylogenetic tree relating UPF0201 family members to L5 ribosomal proteins and other structurally similar RNA binding proteins, thereby expanding our understanding of the evolutionary purview of the RRM superfamily. Analyses of the surfaces of these newly determined UPF0201 structures suggest that they probably do not function as RNA binding proteins, and that this domain specific family of proteins has acquired a novel function in archaebacteria, which awaits experimental elucidation.

  5. Correlating the vibrational spectra of structurally related molecules: A spectroscopic measure of similarity.

    Science.gov (United States)

    Tao, Yunwen; Zou, Wenli; Cremer, Dieter; Kraka, Elfi

    2018-03-05

    Using catastrophe theory and the concept of a mutation path, an algorithm is developed that leads to the direct correlation of the normal vibrational modes of two structurally related molecules. The mutation path is defined by weighted incremental changes in mass and geometry of the molecules in question, which are successively applied to mutate a molecule into a structurally related molecule and thus continuously converting their normal vibrational spectra from one into the other. Correlation diagrams are generated that accurately relate the normal vibrational modes to each other by utilizing mode-mode overlap criteria and resolving allowed and avoided crossings of vibrational eigenstates. The limitations of normal mode correlation, however, foster the correlation of local vibrational modes, which offer a novel vibrational measure of similarity. It will be shown how this will open new avenues for chemical studies. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Effects of species' similarity and dominance on the functional and phylogenetic structure of a plant meta-community.

    Science.gov (United States)

    Chalmandrier, L; Münkemüller, T; Lavergne, S; Thuiller, W

    2015-01-01

    Different assembly processes drive the spatial structure of meta-communities (beta-diversity). Recently, functional and phylogenetic diversities have been suggested as indicators of these assembly processes. Assuming that diversity is a good proxy for niche overlap, high beta-diversity along environmental gradients should be the result of environmental filtering while low beta-diversity should stem from competitive interactions. So far, studies trying to disentangle the relative importance of these assembly processes have provided mixed results. One reason for this may be that these studies often rely on a single measure of diversity and thus implicitly make a choice on how they account for species relative abundances and how species similarities are captured by functional traits or phylogeny. Here, we tested the effect of gradually scaling the importance of dominance (the weight given to dominant vs. rare species) and species similarity (the weight given to small vs. large similarities) on resulting beta-diversity patterns of an alpine plant meta-community. To this end, we combined recent extensions of the Hill numbers framework with Pagel's phylogenetic tree transformation approach. We included functional (based on the leaf-height-seed spectrum) and phylogenetic facets of beta-diversity in our analysis and explicitly accounted for effects of environmental and spatial covariates. We found that functional beta-diversity, was high when the same weight was given to dominant vs. rare species and to large vs. small species' similarities. In contrast, phylogenetic beta-diversity was low when greater weight was given to dominant species and small species' similarities. Those results suggested that different environments along the gradients filtered different species according to their functional traits, while, the same competitive lineages dominated communities across the gradients. Our results highlight that functional vs. phylogenetic facets, presence-absence vs

  7. Similarity search processing. Paralelization and indexing technologies.

    Directory of Open Access Journals (Sweden)

    Eder Dos Santos

    2015-08-01

    The next Scientific-Technical Report addresses the similarity search and the implementation of metric structures on parallel environments. It also presents the state of the art related to similarity search on metric structures and parallelism technologies. Comparative analysis are also proposed, seeking to identify the behavior of a set of metric spaces and metric structures over processing platforms multicore-based and GPU-based.

  8. Ectopic osteogenesis and angiogenesis regulated by porous architecture of hydroxyapatite scaffolds with similar interconnecting structure in vivo

    Science.gov (United States)

    Li, Jinyu; Zhi, Wei; Xu, Taotao; Shi, Feng; Duan, Ke; Wang, Jianxin; Mu, Yandong; Weng, Jie

    2016-01-01

    The macro-pore sizes of porous scaffold play a key role for regulating ectopic osteogenesis and angiogenesis but many researches ignored the influence of interconnection between macro-pores with different sizes. In order to accurately reveal the relationship between ectopic osteogenesis and macro-pore sizes in dorsal muscle and abdominal cavities of dogs, hydroxyapatite (HA) scaffolds with three different macro-pore sizes of 500–650, 750–900 and 1100–1250 µm were prepared via sugar spheres-leaching process, which also had similar interconnecting structure determined by keeping the d/s ratio of interconnecting window diameter to macro-pore size constant. The permeability test showed that the seepage flow of fluid through the porous scaffolds increased with the increase of macro-pore sizes. The cell growth in three scaffolds was not affected by the macro-pore sizes. The in vivo ectopic implantation results indicated that the macro-pore sizes of HA scaffolds with the similar interconnecting structure have impact not only the speed of osteogenesis and angiogenesis but also the space distribution of newly formed bone. The scaffold with macro-pore sizes of 750–900 µm exhibited much faster angiogenesis and osteogenesis, and much more uniformly distribution of new bone than those with other macro-pore sizes. This work illustrates the importance of a suitable macro-pore sizes in HA scaffolds with the similar interconnecting structure which provides the environment for ectopic osteogenesis and angiogenesis. PMID:27699059

  9. Seismodynamics of extended underground structures and soils: Statement of the problem and self-similar solutions

    Science.gov (United States)

    Georgievskii, D. V.; Israilov, M. Sh.

    2015-07-01

    In the problems of common vibrations of extended underground structures (pipelines and tunnels) and soil, an approach of the one-dimensional deformation of the medium is developed; this approach is based on the assumption that the soil deformation in the direction of seismic wave propagation coinciding with the pipeline axis is prevailing. The analytic solutions are obtained in the cases where the wave velocity in the soil is respectively less or greater than the wave velocity in the pipeline. The parameters influencing the pipeline fracture are revealed and methods for increasing the seismic stability of such structures are given. The possibility of the pipeline fatigue fracture is pointed out. The statements and solutions of parabolic problems modeling the physical phenomena in soils in the case of discontinuous velocity on the boundaries at the initial time are given. The notion of generalized vorticity diffusion is introduced and the cases of self-similarity existence are classified. A detailed analysis is performed for the non-Newtonian polynomial fluid, the medium close in properties to the rigidly ideally plastic body, and the viscoplastic Shvedov—Bingham body. In the case of physically linear medium, new self-similar solutions are obtained which describe the process of unsteady axially symmetric shear in spherical coordinates. The first approximation to the asymptotic solution of the problem of the vortex sheet diffusion is constructed in a medium with small polynomial nonlinearity. The solutions polynomially decreasing to zero as the self-similar variable increases are proposed in the class of two-constant fluids.

  10. Revelation of the Sun Self-Similarity Skeletal Structures

    International Nuclear Information System (INIS)

    Rantsev-Kartinov, V.A.

    2005-01-01

    The analysis of databases of photographic images of a surface of the Sun, its atmosphere and the closest its space environment taken at various spatial resolutions and for various types of radiation of a surface of the Sun by means of a method multilevel dynamic contrasting, has revealed presence skeletal structures as on the Sun directly such and in its environment. It is demonstrated the revealed a global structures of the Sun and powerful ejections of mass of its corona, as well as the structures of its atmosphere, protuberances, sun-spots and a globular structures of its photosphere

  11. Reynolds stress structures in a self-similar adverse pressure gradient turbulent boundary layer at the verge of separation.

    Science.gov (United States)

    Atkinson, C.; Sekimoto, A.; Jiménez, J.; Soria, J.

    2018-04-01

    Mean Reynolds stress profiles and instantaneous Reynolds stress structures are investigated in a self-similar adverse pressure gradient turbulent boundary layer (APG-TBL) at the verge of separation using data from direct numerical simulations. The use of a self-similar APG-TBL provides a flow domain in which the flow gradually approaches a constant non-dimensional pressure gradient, resulting in a flow in which the relative contribution of each term in the governing equations is independent of streamwise position over a domain larger than two boundary layer thickness. This allows the flow structures to undergo a development that is less dependent on the upstream flow history when compared to more rapidly decelerated boundary layers. This APG-TBL maintains an almost constant shape factor of H = 2.3 to 2.35 over a momentum thickness based Reynolds number range of Re δ 2 = 8420 to 12400. In the APG-TBL the production of turbulent kinetic energy is still mostly due to the correlation of streamwise and wall-normal fluctuations, 〈uv〉, however the contribution form the other components of the Reynolds stress tensor are no longer negligible. Statistical properties associated with the scale and location of sweeps and ejections in this APG-TBL are compared with those of a zero pressure gradient turbulent boundary layer developing from the same inlet profile, resulting in momentum thickness based range of Re δ 2 = 3400 to 3770. In the APG-TBL the peak in both the mean Reynolds stress and the production of turbulent kinetic energy move from the near wall region out to a point consistent with the displacement thickness height. This is associated with a narrower distribution of the Reynolds stress and a 1.6 times higher relative number of wall-detached negative uv structures. These structures occupy 5 times less of the boundary layer volume and show a similar reduction in their streamwise extent with respect to the boundary layer thickness. A significantly lower percentage

  12. Rapid discovery of peptide capture candidates with demonstrated specificity for structurally similar toxins

    Science.gov (United States)

    Sarkes, Deborah A.; Hurley, Margaret M.; Coppock, Matthew B.; Farrell, Mikella E.; Pellegrino, Paul M.; Stratis-Cullum, Dimitra N.

    2016-05-01

    Peptides have emerged as viable alternatives to antibodies for molecular-based sensing due to their similarity in recognition ability despite their relative structural simplicity. Various methods for peptide capture reagent discovery exist, including phage display, yeast display, and bacterial display. One of the primary advantages of peptide discovery by bacterial display technology is the speed to candidate peptide capture agent, due to both rapid growth of bacteria and direct utilization of the sorted cells displaying each individual peptide for the subsequent round of biopanning. We have previously isolated peptide affinity reagents towards protective antigen of Bacillus anthracis using a commercially available automated magnetic sorting platform with improved enrichment as compared to manual magnetic sorting. In this work, we focus on adapting our automated biopanning method to a more challenging sort, to demonstrate the specificity possible with peptide capture agents. This was achieved using non-toxic, recombinant variants of ricin and abrin, RiVax and abrax, respectively, which are structurally similar Type II ribosomal inactivating proteins with significant sequence homology. After only two rounds of biopanning, enrichment of peptide capture candidates binding abrax but not RiVax was achieved as demonstrated by Fluorescence Activated Cell Sorting (FACS) studies. Further sorting optimization included negative sorting against RiVax, proper selection of autoMACS programs for specific sorting rounds, and using freshly made buffer and freshly thawed protein target for each round of biopanning for continued enrichment over all four rounds. Most of the resulting candidates from biopanning for abrax binding peptides were able to bind abrax but not RiVax, demonstrating that short peptide sequences can be highly specific even at this early discovery stage.

  13. From SNOMED CT to Uberon: Transferability of evaluation methodology between similarly structured ontologies.

    Science.gov (United States)

    Elhanan, Gai; Ochs, Christopher; Mejino, Jose L V; Liu, Hao; Mungall, Christopher J; Perl, Yehoshua

    2017-06-01

    To examine whether disjoint partial-area taxonomy, a semantically-based evaluation methodology that has been successfully tested in SNOMED CT, will perform with similar effectiveness on Uberon, an anatomical ontology that belongs to a structurally similar family of ontologies as SNOMED CT. A disjoint partial-area taxonomy was generated for Uberon. One hundred randomly selected test concepts that overlap between partial-areas were matched to a same size control sample of non-overlapping concepts. The samples were blindly inspected for non-critical issues and presumptive errors first by a general domain expert whose results were then confirmed or rejected by a highly experienced anatomical ontology domain expert. Reported issues were subsequently reviewed by Uberon's curators. Overlapping concepts in Uberon's disjoint partial-area taxonomy exhibited a significantly higher rate of all issues. Clear-cut presumptive errors trended similarly but did not reach statistical significance. A sub-analysis of overlapping concepts with three or more relationship types indicated a much higher rate of issues. Overlapping concepts from Uberon's disjoint abstraction network are quite likely (up to 28.9%) to exhibit issues. The results suggest that the methodology can transfer well between same family ontologies. Although Uberon exhibited relatively few overlapping concepts, the methodology can be combined with other semantic indicators to expand the process to other concepts within the ontology that will generate high yields of discovered issues. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Analysis of network motifs in cellular regulation: Structural similarities, input-output relations and signal integration.

    Science.gov (United States)

    Straube, Ronny

    2017-12-01

    Much of the complexity of regulatory networks derives from the necessity to integrate multiple signals and to avoid malfunction due to cross-talk or harmful perturbations. Hence, one may expect that the input-output behavior of larger networks is not necessarily more complex than that of smaller network motifs which suggests that both can, under certain conditions, be described by similar equations. In this review, we illustrate this approach by discussing the similarities that exist in the steady state descriptions of a simple bimolecular reaction, covalent modification cycles and bacterial two-component systems. Interestingly, in all three systems fundamental input-output characteristics such as thresholds, ultrasensitivity or concentration robustness are described by structurally similar equations. Depending on the system the meaning of the parameters can differ ranging from protein concentrations and affinity constants to complex parameter combinations which allows for a quantitative understanding of signal integration in these systems. We argue that this approach may also be extended to larger regulatory networks. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Identification of structural similarities between putative transmission proteins of Polymyxa and Spongospora transmitted bymoviruses and furoviruses.

    Science.gov (United States)

    Dessens, J T; Meyer, M

    1996-01-01

    Comparison of amino acid sequence and hydropathy profiles shows conserved, structural similarities between the capsid readthrough protein of potato mop top virus (transmitted by Spongospora subterranea) and furovirus and bymovirus proteins implicated in transmission by Polymyxa spp. This suggests that these proteins have a common ancestry and are involved in a common biological process: virus transmission by plasmodiophorid fungi.

  16. Self-similar spectral structures and edge-locking hierarchy in open-boundary spin chains

    International Nuclear Information System (INIS)

    Haque, Masudul

    2010-01-01

    For an anisotropic Heisenberg (XXZ) spin chain, we show that an open boundary induces a series of approximately self-similar features at different energy scales, high up in the eigenvalue spectrum. We present a nonequilibrium phenomenon related to this fractal structure, involving states in which a connected block near the edge is polarized oppositely to the rest of the chain. We show that such oppositely polarized blocks can be 'locked' to the edge of the spin chain and that there is a hierarchy of edge-locking effects at various orders of the anisotropy. The phenomenon enables dramatic control of quantum-state transmission and magnetization control.

  17. Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.

    Directory of Open Access Journals (Sweden)

    Seiichi Tawara

    Full Text Available Fucosylated haptoglobin (Fuc-Hpt and Mac-2 binding protein (Mac-2 bp are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD. We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F ≥ 2. In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F ≥ 3. In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI and Fibrosis-4 (FIB4 index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco-biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C.

  18. ProBiS-2012: web server and web services for detection of structurally similar binding sites in proteins.

    Science.gov (United States)

    Konc, Janez; Janezic, Dusanka

    2012-07-01

    The ProBiS web server is a web server for detection of structurally similar binding sites in the PDB and for local pairwise alignment of protein structures. In this article, we present a new version of the ProBiS web server that is 10 times faster than earlier versions, due to the efficient parallelization of the ProBiS algorithm, which now allows significantly faster comparison of a protein query against the PDB and reduces the calculation time for scanning the entire PDB from hours to minutes. It also features new web services, and an improved user interface. In addition, the new web server is united with the ProBiS-Database and thus provides instant access to pre-calculated protein similarity profiles for over 29 000 non-redundant protein structures. The ProBiS web server is particularly adept at detection of secondary binding sites in proteins. It is freely available at http://probis.cmm.ki.si/old-version, and the new ProBiS web server is at http://probis.cmm.ki.si.

  19. Clustering and visualizing similarity networks of membrane proteins.

    Science.gov (United States)

    Hu, Geng-Ming; Mai, Te-Lun; Chen, Chi-Ming

    2015-08-01

    We proposed a fast and unsupervised clustering method, minimum span clustering (MSC), for analyzing the sequence-structure-function relationship of biological networks, and demonstrated its validity in clustering the sequence/structure similarity networks (SSN) of 682 membrane protein (MP) chains. The MSC clustering of MPs based on their sequence information was found to be consistent with their tertiary structures and functions. For the largest seven clusters predicted by MSC, the consistency in chain function within the same cluster is found to be 100%. From analyzing the edge distribution of SSN for MPs, we found a characteristic threshold distance for the boundary between clusters, over which SSN of MPs could be properly clustered by an unsupervised sparsification of the network distance matrix. The clustering results of MPs from both MSC and the unsupervised sparsification methods are consistent with each other, and have high intracluster similarity and low intercluster similarity in sequence, structure, and function. Our study showed a strong sequence-structure-function relationship of MPs. We discussed evidence of convergent evolution of MPs and suggested applications in finding structural similarities and predicting biological functions of MP chains based on their sequence information. © 2015 Wiley Periodicals, Inc.

  20. CMASA: an accurate algorithm for detecting local protein structural similarity and its application to enzyme catalytic site annotation

    Directory of Open Access Journals (Sweden)

    Li Gong-Hua

    2010-08-01

    Full Text Available Abstract Background The rapid development of structural genomics has resulted in many "unknown function" proteins being deposited in Protein Data Bank (PDB, thus, the functional prediction of these proteins has become a challenge for structural bioinformatics. Several sequence-based and structure-based methods have been developed to predict protein function, but these methods need to be improved further, such as, enhancing the accuracy, sensitivity, and the computational speed. Here, an accurate algorithm, the CMASA (Contact MAtrix based local Structural Alignment algorithm, has been developed to predict unknown functions of proteins based on the local protein structural similarity. This algorithm has been evaluated by building a test set including 164 enzyme families, and also been compared to other methods. Results The evaluation of CMASA shows that the CMASA is highly accurate (0.96, sensitive (0.86, and fast enough to be used in the large-scale functional annotation. Comparing to both sequence-based and global structure-based methods, not only the CMASA can find remote homologous proteins, but also can find the active site convergence. Comparing to other local structure comparison-based methods, the CMASA can obtain the better performance than both FFF (a method using geometry to predict protein function and SPASM (a local structure alignment method; and the CMASA is more sensitive than PINTS and is more accurate than JESS (both are local structure alignment methods. The CMASA was applied to annotate the enzyme catalytic sites of the non-redundant PDB, and at least 166 putative catalytic sites have been suggested, these sites can not be observed by the Catalytic Site Atlas (CSA. Conclusions The CMASA is an accurate algorithm for detecting local protein structural similarity, and it holds several advantages in predicting enzyme active sites. The CMASA can be used in large-scale enzyme active site annotation. The CMASA can be available by the

  1. In Vitro-Assembled Alphavirus Core-Like Particles Maintain a Structure Similar to That of Nucleocapsid Cores in Mature Virus

    OpenAIRE

    Mukhopadhyay, Suchetana; Chipman, Paul R.; Hong, Eunmee M.; Kuhn, Richard J.; Rossmann, Michael G.

    2002-01-01

    In vitro-assembled core-like particles produced from alphavirus capsid protein and nucleic acid were studied by cryoelectron microscopy. These particles were found to have a diameter of 420 Å with 240 copies of the capsid protein arranged in a T=4 icosahedral surface lattice, similar to the nucleocapsid core in mature virions. However, when the particles were subjected to gentle purification procedures, they were damaged, preventing generation of reliable structural information. Similarly, pu...

  2. Renewing the Respect for Similarity

    Directory of Open Access Journals (Sweden)

    Shimon eEdelman

    2012-07-01

    Full Text Available In psychology, the concept of similarity has traditionally evoked a mixture of respect, stemmingfrom its ubiquity and intuitive appeal, and concern, due to its dependence on the framing of the problemat hand and on its context. We argue for a renewed focus on similarity as an explanatory concept, bysurveying established results and new developments in the theory and methods of similarity-preservingassociative lookup and dimensionality reduction — critical components of many cognitive functions, aswell as of intelligent data management in computer vision. We focus in particular on the growing familyof algorithms that support associative memory by performing hashing that respects local similarity, andon the uses of similarity in representing structured objects and scenes. Insofar as these similarity-basedideas and methods are useful in cognitive modeling and in AI applications, they should be included inthe core conceptual toolkit of computational neuroscience.

  3. Pythoscape: a framework for generation of large protein similarity networks.

    Science.gov (United States)

    Barber, Alan E; Babbitt, Patricia C

    2012-11-01

    Pythoscape is a framework implemented in Python for processing large protein similarity networks for visualization in other software packages. Protein similarity networks are graphical representations of sequence, structural and other similarities among proteins for which pairwise all-by-all similarity connections have been calculated. Mapping of biological and other information to network nodes or edges enables hypothesis creation about sequence-structure-function relationships across sets of related proteins. Pythoscape provides several options to calculate pairwise similarities for input sequences or structures, applies filters to network edges and defines sets of similar nodes and their associated data as single nodes (termed representative nodes) for compression of network information and output data or formatted files for visualization.

  4. Structural and functional similarities between osmotin from Nicotiana tabacum seeds and human adiponectin.

    Science.gov (United States)

    Miele, Marco; Costantini, Susan; Colonna, Giovanni

    2011-02-02

    Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the β-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico.

  5. Predicting drug?drug interactions through drug structural similarities and interaction networks incorporating pharmacokinetics and pharmacodynamics knowledge

    OpenAIRE

    Takeda, Takako; Hao, Ming; Cheng, Tiejun; Bryant, Stephen H.; Wang, Yanli

    2017-01-01

    Drug?drug interactions (DDIs) may lead to adverse effects and potentially result in drug withdrawal from the market. Predicting DDIs during drug development would help reduce development costs and time by rigorous evaluation of drug candidates. The primary mechanisms of DDIs are based on pharmacokinetics (PK) and pharmacodynamics (PD). This study examines the effects of 2D structural similarities of drugs on DDI prediction through interaction networks including both PD and PK knowledge. Our a...

  6. A Similarity Search Using Molecular Topological Graphs

    Directory of Open Access Journals (Sweden)

    Yoshifumi Fukunishi

    2009-01-01

    Full Text Available A molecular similarity measure has been developed using molecular topological graphs and atomic partial charges. Two kinds of topological graphs were used. One is the ordinary adjacency matrix and the other is a matrix which represents the minimum path length between two atoms of the molecule. The ordinary adjacency matrix is suitable to compare the local structures of molecules such as functional groups, and the other matrix is suitable to compare the global structures of molecules. The combination of these two matrices gave a similarity measure. This method was applied to in silico drug screening, and the results showed that it was effective as a similarity measure.

  7. Similarity and self-similarity in high energy density physics: application to laboratory astrophysics

    International Nuclear Information System (INIS)

    Falize, E.

    2008-10-01

    The spectacular recent development of powerful facilities allows the astrophysical community to explore, in laboratory, astrophysical phenomena where radiation and matter are strongly coupled. The titles of the nine chapters of the thesis are: from high energy density physics to laboratory astrophysics; Lie groups, invariance and self-similarity; scaling laws and similarity properties in High-Energy-Density physics; the Burgan-Feix-Munier transformation; dynamics of polytropic gases; stationary radiating shocks and the POLAR project; structure, dynamics and stability of optically thin fluids; from young star jets to laboratory jets; modelling and experiences for laboratory jets

  8. Phonological Similarity in American Sign Language.

    Science.gov (United States)

    Hildebrandt, Ursula; Corina, David

    2002-01-01

    Investigates deaf and hearing subjects' ratings of American Sign Language (ASL) signs to assess whether linguistic experience shapes judgments of sign similarity. Findings are consistent with linguistic theories that posit movement and location as core structural elements of syllable structure in ASL. (Author/VWL)

  9. Structural similarities between the tradition of moral philosophy and Durkheim’s social theory

    Directory of Open Access Journals (Sweden)

    Ana Marta González

    2017-05-01

    Full Text Available The first sociological theories are indebted to Enlightenment philosophy of history, which first appeared to provide a framework of meaning for moral action once moral theory had renounced the metaphysical commitments of early modern moral philosophy. While defending the autonomy of sociology from philosophy, Durkheim prescribed a specific task for sociological thought, namely: develop a moral science which, by keeping together the two features with which moral facts appear before conscience —solidarity and coercion— could account for the moral sense of the division of labour, a phenomenon previously considered almost a natural process. The purpose of this article is to show how Durkheim’s approach makes room for us to establish a structural similarity between sociological analysis and the perspective of mutual obligations characteristic of the moral philosophical tradition.

  10. Large-scale structural and textual similarity-based mining of knowledge graph to predict drug-drug interactions

    KAUST Repository

    Abdelaziz, Ibrahim; Fokoue, Achille; Hassanzadeh, Oktie; Zhang, Ping; Sadoghi, Mohammad

    2017-01-01

    Drug-Drug Interactions (DDIs) are a major cause of preventable Adverse Drug Reactions (ADRs), causing a significant burden on the patients’ health and the healthcare system. It is widely known that clinical studies cannot sufficiently and accurately identify DDIs for new drugs before they are made available on the market. In addition, existing public and proprietary sources of DDI information are known to be incomplete and/or inaccurate and so not reliable. As a result, there is an emerging body of research on in-silico prediction of drug-drug interactions. In this paper, we present Tiresias, a large-scale similarity-based framework that predicts DDIs through link prediction. Tiresias takes in various sources of drug-related data and knowledge as inputs, and provides DDI predictions as outputs. The process starts with semantic integration of the input data that results in a knowledge graph describing drug attributes and relationships with various related entities such as enzymes, chemical structures, and pathways. The knowledge graph is then used to compute several similarity measures between all the drugs in a scalable and distributed framework. In particular, Tiresias utilizes two classes of features in a knowledge graph: local and global features. Local features are derived from the information directly associated to each drug (i.e., one hop away) while global features are learnt by minimizing a global loss function that considers the complete structure of the knowledge graph. The resulting similarity metrics are used to build features for a large-scale logistic regression model to predict potential DDIs. We highlight the novelty of our proposed Tiresias and perform thorough evaluation of the quality of the predictions. The results show the effectiveness of Tiresias in both predicting new interactions among existing drugs as well as newly developed drugs.

  11. Large-scale structural and textual similarity-based mining of knowledge graph to predict drug-drug interactions

    KAUST Repository

    Abdelaziz, Ibrahim

    2017-06-12

    Drug-Drug Interactions (DDIs) are a major cause of preventable Adverse Drug Reactions (ADRs), causing a significant burden on the patients’ health and the healthcare system. It is widely known that clinical studies cannot sufficiently and accurately identify DDIs for new drugs before they are made available on the market. In addition, existing public and proprietary sources of DDI information are known to be incomplete and/or inaccurate and so not reliable. As a result, there is an emerging body of research on in-silico prediction of drug-drug interactions. In this paper, we present Tiresias, a large-scale similarity-based framework that predicts DDIs through link prediction. Tiresias takes in various sources of drug-related data and knowledge as inputs, and provides DDI predictions as outputs. The process starts with semantic integration of the input data that results in a knowledge graph describing drug attributes and relationships with various related entities such as enzymes, chemical structures, and pathways. The knowledge graph is then used to compute several similarity measures between all the drugs in a scalable and distributed framework. In particular, Tiresias utilizes two classes of features in a knowledge graph: local and global features. Local features are derived from the information directly associated to each drug (i.e., one hop away) while global features are learnt by minimizing a global loss function that considers the complete structure of the knowledge graph. The resulting similarity metrics are used to build features for a large-scale logistic regression model to predict potential DDIs. We highlight the novelty of our proposed Tiresias and perform thorough evaluation of the quality of the predictions. The results show the effectiveness of Tiresias in both predicting new interactions among existing drugs as well as newly developed drugs.

  12. Glycosaminoglycans analogues from marine invertebrates: structure, biological effects and potential as new therapeutics.

    Directory of Open Access Journals (Sweden)

    Mauro Sergio Pavao

    2014-09-01

    Full Text Available In this review, several glycosaminoglycan analogs obtained from different marine invertebrate are reported. The structure, biological activity and mechanism of action of these unique molecules are detailed reviewed and exemplified by experiments in vitro and in vivo. Among the glycans studied are low-sulfated heparin-like polymers from ascidians, containing significant anticoagulant activity and no bleeding effect; dermatan sulfates with significant neurite outgrowth promoting activity and anti-P-selectin from ascidians, and a unique fucosylated chondroitin sulfate from sea cucumbers, possessing anticoagulant activity after oral administration and high anti P- and L-selectin activities. The therapeutic value and safety of these invertebrate glycans have been extensively proved by several experimental animal models of diseases, including thrombosis, inflammation and metastasis. These invertebrate glycans can be obtained in high concentrations from marine organisms that have been used as a food source for decades, and usually obtained from marine farms in sufficient quantities to be used as starting material for new therapeutics.

  13. Solid-phase extraction NMR studies of chromatographic fractions of saponins from Quillaja saponaria.

    Science.gov (United States)

    Nyberg, Nils T; Baumann, Herbert; Kenne, Lennart

    2003-01-15

    The saponin mixture QH-B from the tree Quillaja saponaria var. Molina was fractionated by RP-HPLC in several steps. The fractions were analyzed by solid-phase extraction NMR (SPE-NMR), a technique combining the workup by solid-phase extraction with on-line coupling to an NMR flow probe. Together with MALDI-TOF mass spectrometry and comparison with chemical shifts of similar saponins, the structures of both major and minor components in QH-B could be obtained. The procedure described is a simple method to determine the structure of components in a complex mixture. The two major fractions of the mixture were found to contain at least 28 saponins, differing in the carbohydrate substructures. Eight of these have not previously been determined. The 28 saponins formed 14 equilibrium pairs by the migration of an O-acyl group between two adjacent positions on a fucosyl residue.

  14. Identification of similar regions of protein structures using integrated sequence and structure analysis tools

    Directory of Open Access Journals (Sweden)

    Heiland Randy

    2006-03-01

    Full Text Available Abstract Background Understanding protein function from its structure is a challenging problem. Sequence based approaches for finding homology have broad use for annotation of both structure and function. 3D structural information of protein domains and their interactions provide a complementary view to structure function relationships to sequence information. We have developed a web site http://www.sblest.org/ and an API of web services that enables users to submit protein structures and identify statistically significant neighbors and the underlying structural environments that make that match using a suite of sequence and structure analysis tools. To do this, we have integrated S-BLEST, PSI-BLAST and HMMer based superfamily predictions to give a unique integrated view to prediction of SCOP superfamilies, EC number, and GO term, as well as identification of the protein structural environments that are associated with that prediction. Additionally, we have extended UCSF Chimera and PyMOL to support our web services, so that users can characterize their own proteins of interest. Results Users are able to submit their own queries or use a structure already in the PDB. Currently the databases that a user can query include the popular structural datasets ASTRAL 40 v1.69, ASTRAL 95 v1.69, CLUSTER50, CLUSTER70 and CLUSTER90 and PDBSELECT25. The results can be downloaded directly from the site and include function prediction, analysis of the most conserved environments and automated annotation of query proteins. These results reflect both the hits found with PSI-BLAST, HMMer and with S-BLEST. We have evaluated how well annotation transfer can be performed on SCOP ID's, Gene Ontology (GO ID's and EC Numbers. The method is very efficient and totally automated, generally taking around fifteen minutes for a 400 residue protein. Conclusion With structural genomics initiatives determining structures with little, if any, functional characterization

  15. The identification and characterization of novel N-glycan-based biomarkers in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Long Liu

    Full Text Available To identify and validate N-glycan biomarkers in gastric cancer (GC and to elucidate their underlying molecular mechanism of action.In total, 347 individuals, including patients with GC (gastric cancer or atrophic gastritis and healthy controls, were randomly divided into a training group (n=287 and a retrospective validation group (n=60. Serum N-glycan profiling was achieved with DNA sequencer-assisted/fluorophore-assisted carbohydrate electrophoresis (DSA-FACE. Two diagnostic models were constructed based on the N-glycan profiles using logistic stepwise regression. The diagnostic performance of each model was assessed in retrospective, prospective (n=60, and follow-up (n=40 cohorts. Lectin blotting was performed to determine total core-fucosylation, and the expression of genes involved in core-fucosylation in GC was analyzed by reverse transcriptase-polymerase chain reaction.We identified at least 9 N-glycan structures (peaks and the levels of core fucose residues and fucosyltransferase were significantly decreased in GC. Two diagnostic models, designated GCglycoA and GCglycoB, were constructed to differentiate GC from control and atrophic gastritis. The areas under the receiver operating characteristic (ROC curves (AUC for both GCglycoA and GCglycoB were higher than those for CEA, CA19-9, CA125 and CA72-4. Compared with CEA, CA19-9, CA125 and CA72-4, the sensitivity of GCglycoA increased 29.66%, 37.28%, 56.78% and 61.86%, respectively, and the accuracy increased 10.62%, 16.82%, 25.67% and 28.76%, respectively. For GCglycoB, the sensitivity increased 27.97%, 35.59%, 55.09% and 60.17% and the accuracy increased 21.26%, 24.64%, 31.40% and 34.30% compared with CEA, CA19-9, CA125 and CA72-4, respectively. After curative surgery, the core fucosylated peak (peak 3 and the total core fucosylated N-glycans (sumfuc were reversed.The results indicated that the diagnostic models based on N-glycan markers are valuable and noninvasive alternatives for

  16. Chemical characterization of milk oligosaccharides of the koala (Phascolarctos cinereus).

    Science.gov (United States)

    Urashima, Tadasu; Taufik, Epi; Fukuda, Rino; Nakamura, Tadashi; Fukuda, Kenji; Saito, Tadao; Messer, Michael

    2013-11-01

    Previous structural characterizations of marsupial milk oligosaccharides had been performed in only two macropod species, the tammar wallaby and the red kangaroo. To clarify the homology and heterogeneity of milk oligosaccharides among marsupial species, which could provide information on their evolution, the oligosaccharides of the koala milk carbohydrate fraction were characterized in this study. Neutral and acidic oligosaccharides were separated from the carbohydrate fraction of milk of the koala, a non-macropod marsupial, and characterized by (1)H-nuclear magnetic resonance spectroscopy. The structures of the neutral saccharides were found to be Gal(β1-4)Glc (lactose), Gal(β1-3)Gal(β1-4)Glc (3'-galactosyllactose), Gal(β1-3)Gal(β1-3)Gal(β1-4)Glc (3',3″-digalactosyllactose), Gal(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (lacto-N-novopentaose I) and Gal(β1-3){Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-6)}Gal(β1-4)Glc (fucosyl lacto-N-novopentaose I), while those of the acidic saccharides were Neu5Ac(α2-3)Gal(β1-4)Glc (3'-SL), Neu5Ac(α2-3)Gal(β1-3)Gal(β1-4)Gal (sialyl 3'-galactosyllactose), Neu5Ac(α2-3)Gal(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (sialyl lacto-N-novopentaose a), Gal(β1-3)[Neu5Ac(α2-6)Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (sialyl lacto-N-novopentaose b), Gal(β1-3)[Neu5Ac(α2-3)Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (sialyl lacto-N-novopentaose c), and Neu5Ac(α2-3)Gal(β1-3){Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-6)}Gal(β1-4)Glc (fucosyl sialyl lacto-N-novopentaose a). The neutral oligosaccharides, other than fucosyl lacto-N-novopentaose I, a novel hexasaccharide, had been found in milk of the tammar wallaby, a macropod marsupial, while the acidic oligosaccharides, other than fucosyl sialyl lacto-N-novopentaose a had been identified in milk carbohydrate of the red kangaroo. The presence of fucosyl oligosaccharides is a significant feature of koala milk, in which it differs from milk of the tammar wallaby and the red kangaroo.

  17. Production of human milk oligosaccharides by enzymatic and whole-cell microbial biotransformations.

    Science.gov (United States)

    Sprenger, Georg A; Baumgärtner, Florian; Albermann, Christoph

    2017-09-20

    Human milk oligosaccharides (HMO) are almost unique constituents of breast milk and are not found in appreciable amounts in cow milk. Due to several positive aspects of HMO for the development, health, and wellbeing of infants, production of HMO would be desirable. As a result, scientists from different disciplines have developed methods for the preparation of single HMO compounds. Here, we review approaches to HMO preparation by (chemo-)enzymatic syntheses or by whole-cell biotransformation with recombinant bacterial cells. With lactose as acceptor (in vitro or in vivo), fucosyltransferases can be used for the production of 2'-fucosyllactose, 3-fucosyllactose, or more complex fucosylated core structures. Sialylated HMO can be produced by sialyltransferases and trans-sialidases. Core structures as lacto-N-tetraose can be obtained by glycosyltransferases from chemical donor compounds or by multi-enzyme cascades; recent publications also show production of lacto-N-tetraose by recombinant Escherichia coli bacteria and approaches to obtain fucosylated core structures. In view of an industrial production of HMOs, the whole cell biotransformation is at this stage the most promising option to provide human milk oligosaccharides as food additive. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure.

    Science.gov (United States)

    Zhao, Bo; Wang, Xue-Qing; Wang, Xiao-You; Zhang, Hua; Dai, Wen-Bing; Wang, Jun; Zhong, Zhen-Lin; Wu, Hou-Nan; Zhang, Qiang

    2013-10-03

    Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research. Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared. In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice. All the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs. These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more

  19. Complex overlapping concepts: An effective auditing methodology for families of similarly structured BioPortal ontologies.

    Science.gov (United States)

    Zheng, Ling; Chen, Yan; Elhanan, Gai; Perl, Yehoshua; Geller, James; Ochs, Christopher

    2018-05-28

    In previous research, we have demonstrated for a number of ontologies that structurally complex concepts (for different definitions of "complex") in an ontology are more likely to exhibit errors than other concepts. Thus, such complex concepts often become fertile ground for quality assurance (QA) in ontologies. They should be audited first. One example of complex concepts is given by "overlapping concepts" (to be defined below.) Historically, a different auditing methodology had to be developed for every single ontology. For better scalability and efficiency, it is desirable to identify family-wide QA methodologies. Each such methodology would be applicable to a whole family of similar ontologies. In past research, we had divided the 685 ontologies of BioPortal into families of structurally similar ontologies. We showed for four ontologies of the same large family in BioPortal that "overlapping concepts" are indeed statistically significantly more likely to exhibit errors. In order to make an authoritative statement concerning the success of "overlapping concepts" as a methodology for a whole family of similar ontologies (or of large subhierarchies of ontologies), it is necessary to show that "overlapping concepts" have a higher likelihood of errors for six out of six ontologies of the family. In this paper, we are demonstrating for two more ontologies that "overlapping concepts" can successfully predict groups of concepts with a higher error rate than concepts from a control group. The fifth ontology is the Neoplasm subhierarchy of the National Cancer Institute thesaurus (NCIt). The sixth ontology is the Infectious Disease subhierarchy of SNOMED CT. We demonstrate quality assurance results for both of them. Furthermore, in this paper we observe two novel, important, and useful phenomena during quality assurance of "overlapping concepts." First, an erroneous "overlapping concept" can help with discovering other erroneous "non-overlapping concepts" in its vicinity

  20. Assessment of Vegetation Structural Diversity and Similarity Index of ...

    African Journals Online (AJOL)

    Data were analysed using descriptive statistics, relative density, diversity and similarity indices. The result showed that the forest reserve has one hundred and ninety species of plants belonging to sixty three families. The dominant plant families recorded in the forest are Leguminosae (12.63%), Rubiaceae (8.42%), ...

  1. A tale of two pectins: Diverse fine structures can result from identical processive PME treatments on similar high DM subtrates

    Science.gov (United States)

    The effects of a processive pectin-methylesterase treatment on two different pectins, both possessing a high degree of methylesterification, were investigated. While the starting samples were purportedly very similar in fine structure, and even though the sample-averaged degree of methylesterificati...

  2. The effects of similarity of theme and instantiation in analogical reasoning.

    Science.gov (United States)

    Yanowitz, K L

    2001-01-01

    The influence of 2 types of structural similarity on analogical reasoning was examined. The theme of a story is a structural component that constrains other relationships in the story. Another structural component is the way in which the theme is implemented. Participants received pairs of stories that varied in the similarity of these two components. Participants in Experiment 1 judged stories containing similar themes as more analogous than stories with dissimilar themes. Likewise, stories with similar implementations were judged as more analogous than stories with dissimilar implementations. Experiment 2 revealed a similar pattern when participants had the opportunity to transfer information from source to target stories. Greater transfer was seen for stories with similar themes than for stories with dissimilar themes. Greater transfer was also seen for stories with similar implementations of different themes than for stories with different implementations.

  3. Mechanics of ultra-stretchable self-similar serpentine interconnects

    International Nuclear Information System (INIS)

    Zhang, Yihui; Fu, Haoran; Su, Yewang; Xu, Sheng

    2013-01-01

    Graphical abstract: We developed analytical models of flexibility and elastic-stretchability for self-similar interconnect. The analytic solutions agree very well with the finite element analyses, both demonstrating that the elastic-stretchability more than doubles when the order of self-similar structure increases by one. Design optimization yields 90% and 50% elastic stretchability for systems with surface filling ratios of 50% and 70% of active devices, respectively. The analytic models are useful for the development of stretchable electronics that simultaneously demand large coverage of active devices, such as stretchable photovoltaics and electronic eye-ball cameras. -- Abstract: Electrical interconnects that adopt self-similar, serpentine layouts offer exceptional levels of stretchability in systems that consist of collections of small, non-stretchable active devices in the so-called island–bridge design. This paper develops analytical models of flexibility and elastic stretchability for such structures, and establishes recursive formulae at different orders of self-similarity. The analytic solutions agree well with finite element analysis, with both demonstrating that the elastic stretchability more than doubles when the order of the self-similar structure increases by one. Design optimization yields 90% and 50% elastic stretchability for systems with surface filling ratios of 50% and 70% of active devices, respectively

  4. Fold-recognition and comparative modeling of human α2,3-sialyltransferases reveal their sequence and structural similarities to CstII from Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Balaji Petety V

    2006-04-01

    Full Text Available Abstract Background The 3-D structure of none of the eukaryotic sialyltransferases (SiaTs has been determined so far. Sequence alignment algorithms such as BLAST and PSI-BLAST could not detect a homolog of these enzymes from the protein databank. SiaTs, thus, belong to the hard/medium target category in the CASP experiments. The objective of the current work is to model the 3-D structures of human SiaTs which transfer the sialic acid in α2,3-linkage viz., ST3Gal I, II, III, IV, V, and VI, using fold-recognition and comparative modeling methods. The pair-wise sequence similarity among these six enzymes ranges from 41 to 63%. Results Unlike the sequence similarity servers, fold-recognition servers identified CstII, a α2,3/8 dual-activity SiaT from Campylobacter jejuni as the homolog of all the six ST3Gals; the level of sequence similarity between CstII and ST3Gals is only 15–20% and the similarity is restricted to well-characterized motif regions of ST3Gals. Deriving template-target sequence alignments for the entire ST3Gal sequence was not straightforward: the fold-recognition servers could not find a template for the region preceding the L-motif and that between the L- and S-motifs. Multiple structural templates were identified to model these regions and template identification-modeling-evaluation had to be performed iteratively to choose the most appropriate templates. The modeled structures have acceptable stereochemical properties and are also able to provide qualitative rationalizations for some of the site-directed mutagenesis results reported in literature. Apart from the predicted models, an unexpected but valuable finding from this study is the sequential and structural relatedness of family GT42 and family GT29 SiaTs. Conclusion The modeled 3-D structures can be used for docking and other modeling studies and for the rational identification of residues to be mutated to impart desired properties such as altered stability, substrate

  5. HIV and influenza share a similar structural blueprint

    Science.gov (United States)

    HIV uses a protein called the envelope glycoprotein spike to attach itself and fuse with the cell membrane; NCI scientists have now defined the structure of this spike in its pre-fusion state using cryo-electron microscopy

  6. Self-similarity in the equation of motion of a ship

    Directory of Open Access Journals (Sweden)

    Gyeong Joong Lee

    2014-06-01

    Full Text Available If we want to analyze the motion of a body in fluid, we should use rigid-body dynamics and fluid dynamics together. Even if the rigid-body and fluid dynamics are each self-consistent, there arises the problem of self-similar structure in the equation of motion when the two dynamics are coupled with each other. When the added mass is greater than the mass of a body, the calculated motion is divergent because of its self-similar structure. This study showed that the above problem is an inherent problem. This problem of self-similar structure may arise in the equation of motion in which the fluid dynamic forces are treated as external forces on the right hand side of the equation. A reconfiguration technique for the equation of motion using pseudo-added-mass was proposed to resolve the self-similar structure problem; specifically for the case when the fluid force is expressed by integration of the fluid pressure.

  7. Stochastic self-similar and fractal universe

    International Nuclear Information System (INIS)

    Iovane, G.; Laserra, E.; Tortoriello, F.S.

    2004-01-01

    The structures formation of the Universe appears as if it were a classically self-similar random process at all astrophysical scales. An agreement is demonstrated for the present hypotheses of segregation with a size of astrophysical structures by using a comparison between quantum quantities and astrophysical ones. We present the observed segregated Universe as the result of a fundamental self-similar law, which generalizes the Compton wavelength relation. It appears that the Universe has a memory of its quantum origin as suggested by R. Penrose with respect to quasi-crystal. A more accurate analysis shows that the present theory can be extended from the astrophysical to the nuclear scale by using generalized (stochastically) self-similar random process. This transition is connected to the relevant presence of the electromagnetic and nuclear interactions inside the matter. In this sense, the presented rule is correct from a subatomic scale to an astrophysical one. We discuss the near full agreement at organic cell scale and human scale too. Consequently the Universe, with its structures at all scales (atomic nucleus, organic cell, human, planet, solar system, galaxy, clusters of galaxy, super clusters of galaxy), could have a fundamental quantum reason. In conclusion, we analyze the spatial dimensions of the objects in the Universe as well as space-time dimensions. The result is that it seems we live in an El Naschie's E-infinity Cantorian space-time; so we must seriously start considering fractal geometry as the geometry of nature, a type of arena where the laws of physics appear at each scale in a self-similar way as advocated long ago by the Swedish school of astrophysics

  8. Multidimensional Riemann problem with self-similar internal structure. Part II - Application to hyperbolic conservation laws on unstructured meshes

    Science.gov (United States)

    Balsara, Dinshaw S.; Dumbser, Michael

    2015-04-01

    Multidimensional Riemann solvers that have internal sub-structure in the strongly-interacting state have been formulated recently (D.S. Balsara (2012, 2014) [5,16]). Any multidimensional Riemann solver operates at the grid vertices and takes as its input all the states from its surrounding elements. It yields as its output an approximation of the strongly interacting state, as well as the numerical fluxes. The multidimensional Riemann problem produces a self-similar strongly-interacting state which is the result of several one-dimensional Riemann problems interacting with each other. To compute this strongly interacting state and its higher order moments we propose the use of a Galerkin-type formulation to compute the strongly interacting state and its higher order moments in terms of similarity variables. The use of substructure in the Riemann problem reduces numerical dissipation and, therefore, allows a better preservation of flow structures, like contact and shear waves. In this second part of a series of papers we describe how this technique is extended to unstructured triangular meshes. All necessary details for a practical computer code implementation are discussed. In particular, we explicitly present all the issues related to computational geometry. Because these Riemann solvers are Multidimensional and have Self-similar strongly-Interacting states that are obtained by Consistency with the conservation law, we call them MuSIC Riemann solvers. (A video introduction to multidimensional Riemann solvers is available on http://www.elsevier.com/xml/linking-roles/text/html". The MuSIC framework is sufficiently general to handle general nonlinear systems of hyperbolic conservation laws in multiple space dimensions. It can also accommodate all self-similar one-dimensional Riemann solvers and subsequently produces a multidimensional version of the same. In this paper we focus on unstructured triangular meshes. As examples of different systems of conservation laws we

  9. Pythoscape: A framework for generation of large protein similarity networks

    OpenAIRE

    Babbitt, Patricia; Barber, AE; Babbitt, PC

    2012-01-01

    Pythoscape is a framework implemented in Python for processing large protein similarity networks for visualization in other software packages. Protein similarity networks are graphical representations of sequence, structural and other similarities among pr

  10. Solenopsis invicta virus 3: mapping of structural proteins, ribosomal frameshifting, and similarities to Acyrthosiphon pisum virus and Kelp fly virus.

    Directory of Open Access Journals (Sweden)

    Steven M Valles

    Full Text Available Solenopsis invicta virus 3 (SINV-3 is a positive-sense single-stranded RNA virus that infects the red imported fire ant, Solenopsis invicta. We show that the second open reading frame (ORF of the dicistronic genome is expressed via a frameshifting mechanism and that the sequences encoding the structural proteins map to both ORF2 and the 3' end of ORF1, downstream of the sequence that encodes the RNA-dependent RNA polymerase. The genome organization and structural protein expression strategy resemble those of Acyrthosiphon pisum virus (APV, an aphid virus. The capsid protein that is encoded by the 3' end of ORF1 in SINV-3 and APV is predicted to have a jelly-roll fold similar to the capsid proteins of picornaviruses and caliciviruses. The capsid-extension protein that is produced by frameshifting, includes the jelly-roll fold domain encoded by ORF1 as its N-terminus, while the C-terminus encoded by the 5' half of ORF2 has no clear homology with other viral structural proteins. A third protein, encoded by the 3' half of ORF2, is associated with purified virions at sub-stoichiometric ratios. Although the structural proteins can be translated from the genomic RNA, we show that SINV-3 also produces a subgenomic RNA encoding the structural proteins. Circumstantial evidence suggests that APV may also produce such a subgenomic RNA. Both SINV-3 and APV are unclassified picorna-like viruses distantly related to members of the order Picornavirales and the family Caliciviridae. Within this grouping, features of the genome organization and capsid domain structure of SINV-3 and APV appear more similar to caliciviruses, perhaps suggesting the basis for a "Calicivirales" order.

  11. Testing statistical significance scores of sequence comparison methods with structure similarity

    Directory of Open Access Journals (Sweden)

    Leunissen Jack AM

    2006-10-01

    Full Text Available Abstract Background In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical significance testing for an alignment. The e-value is the most commonly used statistical validation method for sequence database searching. The CluSTr database and the Protein World database have been created using an alternative statistical significance test: a Z-score based on Monte-Carlo statistics. Several papers have described the superiority of the Z-score as compared to the e-value, using simulated data. We were interested if this could be validated when applied to existing, evolutionary related protein sequences. Results All experiments are performed on the ASTRAL SCOP database. The Smith-Waterman sequence comparison algorithm with both e-value and Z-score statistics is evaluated, using ROC, CVE and AP measures. The BLAST and FASTA algorithms are used as reference. We find that two out of three Smith-Waterman implementations with e-value are better at predicting structural similarities between proteins than the Smith-Waterman implementation with Z-score. SSEARCH especially has very high scores. Conclusion The compute intensive Z-score does not have a clear advantage over the e-value. The Smith-Waterman implementations give generally better results than their heuristic counterparts. We recommend using the SSEARCH algorithm combined with e-values for pairwise sequence comparisons.

  12. Structure and floristic similarities of upper montane forests in Serra Fina mountain range, southeastern Brazil

    Directory of Open Access Journals (Sweden)

    Leonardo Dias Meireles

    2015-03-01

    Full Text Available The upper montane forests in the southern and southeastern regions of Brazil have an unusual and discontinuous geographic distribution at the top of the Atlantic coastal mountain ranges. To describe the floristic composition and structure of the Atlantic Forest near its upper altitudinal limit in southeastern Brazil, 30 plots with 10 × 10 m were installed in three forest sites between 2,200 and 2,300 m.a.s.l. at Serra Fina. The floristic composition and phytosociological structure of this forest were compared with other montane and upper montane forests. In total, 704 individuals were included, belonging to 24 species, 15 families, and 19 genera. Myrsinaceae, Myrtaceae, Symplocaceae, and Cunoniaceae were the most important families, and Myrsine gardneriana, Myrceugenia alpigena, Weinmannia humilis, and Symplocos corymboclados were the most important species. The three forest sites revealed differences in the abundance of species, density, canopy height, and number of stems per individual. The upper montane forests showed structural similarities, such as lower richness, diversity, and effective number of species, and they tended to have higher total densities and total dominance per hectare to montane forests. The most important species in these upper montane forests belong to Austral-Antartic genera or neotropical and pantropical genera that are typical of montane areas. The high number of species shared by these forests suggests past connections between the vegetation in southern Brazilian high-altitude areas.

  13. On the use of the fictitious wave steepness and related surf-similarity parameters in methods that describe the hydraulic and structural response to waves

    NARCIS (Netherlands)

    Heineke, D.; Verhagen, H.J.

    2007-01-01

    To assess the hydraulic performance of coastal structures - viz. wave run-up, overtopping and reflection - and to evaluate the stability of the armour layers, use is made of the dimensionless surf similarity parameter, as introduced by Battjes (1974). The front side slope of the structure and the

  14. On the nature of structural disorder in calcium silicate hydrates with a calcium/silicon ratio similar to tobermorite

    Energy Technology Data Exchange (ETDEWEB)

    Grangeon, Sylvain, E-mail: S.Grangeon@brgm.fr [BRGM, 3, Avenue Claude Guillemin, 45060 Orléans Cedex 2 (France); Claret, Francis; Lerouge, Catherine [BRGM, 3, Avenue Claude Guillemin, 45060 Orléans Cedex 2 (France); Warmont, Fabienne [CRMD, UMR 6619 – CNRS, 1b rue de la férollerie, 45071 Orléans Cedex 2 (France); Sato, Tsutomu; Anraku, Sohtaro [Laboratory of Environmental Geology, Research Group of Geoenvironmental/Engineering Division of Solid Waste, Resources and Geoenvironmental/Engineering Graduate School of Engineering, Hokkaido University, Kita 13 Nishi 8, Sapporo 060-8628 (Japan); Numako, Chiya [Faculty of Integrated Arts and Sciences, The University of Tokushima, 1-1, Minami-Josanjima, Tokushima, 770-8502 (Japan); Linard, Yannick [ANDRA, Centre de Meuse/Haute Marne, 55290 Bure (France); Lanson, Bruno [ISTerre, Grenoble University, CNRS, F-38041 Grenoble (France)

    2013-10-15

    Four calcium silicate hydrates (C-S-H) with structural calcium/silicon (Ca/Si) ratios ranging from 0.82 ± 0.02 to 0.87 ± 0.02 were synthesized at room temperature, 50, 80, and 110 °C. Their structure was elucidated by collating information from electron probe micro-analysis, transmission electron microscopy, extended X-ray absorption fine structure spectroscopy, and powder X-ray diffraction (XRD). A modeling approach specific to defective minerals was used because sample turbostratism prevented analysis using usual XRD refinement techniques (e.g. Rietveld analysis). It is shown that C-S-H with Ca/Si ratio of ∼ 0.8 are structurally similar to nano-crystalline turbostratic tobermorite, a naturally occurring mineral. Their structure thus consists of sheets of calcium atoms in 7-fold coordination, covered by ribbons of silicon tetrahedra with a dreierketten (wollastonite-like) organization. In these silicate ribbons, 0.42 Si per bridging tetrahedron are missing. Random stacking faults occur systematically between successive layers (turbostratic stacking). Layer-to-layer distance is equal to 11.34 Å. Crystallites have a mean size of 10 nm in the a–b plane, and a mean number of 2.6–2.9 layers stacked coherently along the c* axis.

  15. Similar Fracture Patterns in Human Nose and Gothic Cathedral.

    Science.gov (United States)

    Lee, Shu Jin; Tse, Kwong Ming; Lee, Heow Pueh

    2015-10-01

    This study proposes that the bony anatomy of the human nose and masonry structure of the Gothic cathedral are geometrically similar, and have common fracture patterns. We also aim to correlate the fracture patterns observed in patients' midface structures with those seen in the Gothic cathedral using computational approach. CT scans of 33 patients with facial fractures were examined and compared with computer simulations of both the Gothic cathedral and human nose. Three similar patterns were found: (1) Cracks of the nasal arch with crumpling of the vertical buttresses akin to the damage seen during minor earthquakes; (2) lateral deviation of the central nasal arch and collapse of the vertical buttresses akin to those due to lateral forces from wind and in major earthquakes; and (3) Central arch collapse seen as a result of collapse under excessive dead weight. Interestingly, the finding of occult nasal and septal fractures in the mandible fractures with absence of direct nasal trauma highlights the possibility of transmission of forces from the foundation to the arch leading to structural failure. It was also found that the structural buttresses of the Gothic cathedral delineate the vertical buttresses in the human midface structure. These morphologic similarities between the human nose and Gothic cathedral will serve as a basis to study the biomechanics of nasal fractures. Identification of structural buttresses in a skeletal structure has important implications for reconstruction as reestablishment of structural continuity restores normal anatomy and architectural stability of the human midface structure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. A study of concept-based similarity approaches for recommending program examples

    Science.gov (United States)

    Hosseini, Roya; Brusilovsky, Peter

    2017-07-01

    This paper investigates a range of concept-based example recommendation approaches that we developed to provide example-based problem-solving support in the domain of programming. The goal of these approaches is to offer students a set of most relevant remedial examples when they have trouble solving a code comprehension problem where students examine a program code to determine its output or the final value of a variable. In this paper, we use the ideas of semantic-level similarity-based linking developed in the area of intelligent hypertext to generate examples for the given problem. To determine the best-performing approach, we explored two groups of similarity approaches for selecting examples: non-structural approaches focusing on examples that are similar to the problem in terms of concept coverage and structural approaches focusing on examples that are similar to the problem by the structure of the content. We also explored the value of personalized example recommendation based on student's knowledge levels and learning goal of the exercise. The paper presents concept-based similarity approaches that we developed, explains the data collection studies and reports the result of comparative analysis. The results of our analysis showed better ranking performance of the personalized structural variant of cosine similarity approach.

  17. Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase

    International Nuclear Information System (INIS)

    Wu, Zhengliang L.; Zhou, Hui; Ethen, Cheryl M.; Reinhold, Vernon N.

    2016-01-01

    The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and "3H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain why

  18. Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Zhou, Hui [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States); Ethen, Cheryl M. [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States)

    2016-04-29

    The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and {sup 3}H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain

  19. Monin-Obukhov Similarity Functions of the Structure Parameter of Temperature and Turbulent Kinetic Energy Dissipation Rate in the Stable Boundary Layer

    NARCIS (Netherlands)

    Hartogensis, O.K.; Debruin, H.A.R.

    2005-01-01

    The Monin-Obukhov similarity theory (MOST) functions fepsi; and fT, of the dissipation rate of turbulent kinetic energy (TKE), ¿, and the structure parameter of temperature, CT2, were determined for the stable atmospheric surface layer using data gathered in the context of CASES-99. These data cover

  20. Notions of similarity for systems biology models.

    Science.gov (United States)

    Henkel, Ron; Hoehndorf, Robert; Kacprowski, Tim; Knüpfer, Christian; Liebermeister, Wolfram; Waltemath, Dagmar

    2018-01-01

    Systems biology models are rapidly increasing in complexity, size and numbers. When building large models, researchers rely on software tools for the retrieval, comparison, combination and merging of models, as well as for version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of 'similarity' may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here we survey existing methods for the comparison of models, introduce quantitative measures for model similarity, and discuss potential applications of combined similarity measures. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on a combination of different model aspects. The six aspects that we define as potentially relevant for similarity are underlying encoding, references to biological entities, quantitative behaviour, qualitative behaviour, mathematical equations and parameters and network structure. We argue that future similarity measures will benefit from combining these model aspects in flexible, problem-specific ways to mimic users' intuition about model similarity, and to support complex model searches in databases. © The Author 2016. Published by Oxford University Press.

  1. Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.

    Science.gov (United States)

    Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J; Liu, Jennifer

    ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

  2. Contributions of pitch contour, tonality, rhythm, and meter to melodic similarity.

    Science.gov (United States)

    Prince, Jon B

    2014-12-01

    The identity of a melody resides in its sequence of pitches and durations, both of which exhibit surface details as well as structural properties. In this study, pitch contour (pattern of ups and downs) served as pitch surface information, and tonality (musical key) as pitch structure; in the temporal dimension, surface information was the ordinal duration ratios of adjacent notes (rhythm), and meter (beat, or pulse) comprised the structure. Factorially manipulating the preservation or alteration of all of these forms of information in 17 novel melodies (typifying Western music) enabled measuring their effect on perceived melodic similarity. In Experiment 1, 34 participants (varied musical training) rated the perceived similarity of melody pairs transposed to new starting pitches. Rhythm was the largest contributor to perceived similarity, then contour, meter, and tonality. Experiment 2 used the same melodies but varied the tempo within a pair, and added a prefix of 3 chords, which oriented the listener to the starting pitch and tempo before the melody began. Now contour was the strongest influence on similarity ratings, followed by tonality, and then rhythm; meter was not significant. Overall, surface features influenced perceived similarity more than structural, but both had observable effects. The primary theoretical advances in melodic similarity research are that (a) the relative emphasis on pitch and temporal factors is flexible; (b) pitch and time functioned independently when factorially manipulated, regardless of which dimension is more influential; and (c) interactions between surface and structural information were unreliable and never occurred between dimensions. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  3. Asymmetry quantification from reflectance images of orthotic patients using structural similarity metrics

    Science.gov (United States)

    Boucher, Marc-Antoine; Watts, Nicolas; Gremillet, Frederic; Legare, Philippe; Kadoury, Samuel

    2018-02-01

    Pathologies like plantar fasciitis, a common soft tissue disorder of the foot, is frequently associated with older age, high BMI and little exercise. Like other pathologies associated with the foot, the knee or hip, foot orthoses can help the patient's posture and recent techniques allow the creation of personalized foot orthoses based on 3D foot model that are fitted with high accuracy to the foot surface. In order to assess the efficacy of the personalized orthoses on the patient's pose and balance, depth images with reflectance camera filters are acquired in order to evaluate the posture of the patient before and after the use of the orthoses. Images are analysed by clinicians to assess the region asymmetry and posture changes. However, this remains a subjective evaluation and a quantifiable measurement is required to follow patient progression. In this paper, we present a novel tool to assess and quantify the asymmetry of body regions using a color-based structural similarity metric calculated from paired regions. This provides a quantitative measure to evaluate the effect of the personalized orthoses on the patient. A user-friendly interface allows the user to select an area of the body and automatically generate a symmetry axis, along with a measure of asymmetry measuring reflectance variations from the skin. The tool was validated on 30 patients, demonstrating an 83% agreement rate compare to clinical observations.

  4. Notions of similarity for computational biology models

    KAUST Repository

    Waltemath, Dagmar

    2016-03-21

    Computational models used in biology are rapidly increasing in complexity, size, and numbers. To build such large models, researchers need to rely on software tools for model retrieval, model combination, and version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of similarity may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here, we introduce a general notion of quantitative model similarities, survey the use of existing model comparison methods in model building and management, and discuss potential applications of model comparison. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on different model aspects. Potentially relevant aspects of a model comprise its references to biological entities, network structure, mathematical equations and parameters, and dynamic behaviour. Future similarity measures could combine these model aspects in flexible, problem-specific ways in order to mimic users\\' intuition about model similarity, and to support complex model searches in databases.

  5. Notions of similarity for computational biology models

    KAUST Repository

    Waltemath, Dagmar; Henkel, Ron; Hoehndorf, Robert; Kacprowski, Tim; Knuepfer, Christian; Liebermeister, Wolfram

    2016-01-01

    Computational models used in biology are rapidly increasing in complexity, size, and numbers. To build such large models, researchers need to rely on software tools for model retrieval, model combination, and version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of similarity may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here, we introduce a general notion of quantitative model similarities, survey the use of existing model comparison methods in model building and management, and discuss potential applications of model comparison. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on different model aspects. Potentially relevant aspects of a model comprise its references to biological entities, network structure, mathematical equations and parameters, and dynamic behaviour. Future similarity measures could combine these model aspects in flexible, problem-specific ways in order to mimic users' intuition about model similarity, and to support complex model searches in databases.

  6. Similarity indices I: what do they measure

    International Nuclear Information System (INIS)

    Johnston, J.W.

    1976-11-01

    A method for estimating the effects of environmental effusions on ecosystems is described. The characteristics of 25 similarity indices used in studies of ecological communities were investigated. The type of data structure, to which these indices are frequently applied, was described as consisting of vectors of measurements on attributes (species) observed in a set of samples. A general similarity index was characterized as the result of a two-step process defined on a pair of vectors. In the first step an attribute similarity score is obtained for each attribute by comparing the attribute values observed in the pair of vectors. The result is a vector of attribute similarity scores. These are combined in the second step to arrive at the similarity index. The operation in the first step was characterized as a function, g, defined on pairs of attribute values. The second operation was characterized as a function, F, defined on the vector of attribute similarity scores from the first step. Usually, F was a simple sum or weighted sum of the attribute similarity scores. It is concluded that similarity indices should not be used as the test statistic to discriminate between two ecological communities

  7. Similarity indices I: what do they measure.

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, J.W.

    1976-11-01

    A method for estimating the effects of environmental effusions on ecosystems is described. The characteristics of 25 similarity indices used in studies of ecological communities were investigated. The type of data structure, to which these indices are frequently applied, was described as consisting of vectors of measurements on attributes (species) observed in a set of samples. A general similarity index was characterized as the result of a two-step process defined on a pair of vectors. In the first step an attribute similarity score is obtained for each attribute by comparing the attribute values observed in the pair of vectors. The result is a vector of attribute similarity scores. These are combined in the second step to arrive at the similarity index. The operation in the first step was characterized as a function, g, defined on pairs of attribute values. The second operation was characterized as a function, F, defined on the vector of attribute similarity scores from the first step. Usually, F was a simple sum or weighted sum of the attribute similarity scores. It is concluded that similarity indices should not be used as the test statistic to discriminate between two ecological communities.

  8. Accurate protein structure annotation through competitive diffusion of enzymatic functions over a network of local evolutionary similarities.

    Directory of Open Access Journals (Sweden)

    Eric Venner

    Full Text Available High-throughput Structural Genomics yields many new protein structures without known molecular function. This study aims to uncover these missing annotations by globally comparing select functional residues across the structural proteome. First, Evolutionary Trace Annotation, or ETA, identifies which proteins have local evolutionary and structural features in common; next, these proteins are linked together into a proteomic network of ETA similarities; then, starting from proteins with known functions, competing functional labels diffuse link-by-link over the entire network. Every node is thus assigned a likelihood z-score for every function, and the most significant one at each node wins and defines its annotation. In high-throughput controls, this competitive diffusion process recovered enzyme activity annotations with 99% and 97% accuracy at half-coverage for the third and fourth Enzyme Commission (EC levels, respectively. This corresponds to false positive rates 4-fold lower than nearest-neighbor and 5-fold lower than sequence-based annotations. In practice, experimental validation of the predicted carboxylesterase activity in a protein from Staphylococcus aureus illustrated the effectiveness of this approach in the context of an increasingly drug-resistant microbe. This study further links molecular function to a small number of evolutionarily important residues recognizable by Evolutionary Tracing and it points to the specificity and sensitivity of functional annotation by competitive global network diffusion. A web server is at http://mammoth.bcm.tmc.edu/networks.

  9. Assessing Analytical Similarity of Proposed Amgen Biosimilar ABP 501 to Adalimumab.

    Science.gov (United States)

    Liu, Jennifer; Eris, Tamer; Li, Cynthia; Cao, Shawn; Kuhns, Scott

    2016-08-01

    ABP 501 is being developed as a biosimilar to adalimumab. Comprehensive comparative analytical characterization studies have been conducted and completed. The objective of this study was to assess analytical similarity between ABP 501 and two adalimumab reference products (RPs), licensed by the United States Food and Drug Administration (adalimumab [US]) and authorized by the European Union (adalimumab [EU]), using state-of-the-art analytical methods. Comprehensive analytical characterization incorporating orthogonal analytical techniques was used to compare products. Physicochemical property comparisons comprised the primary structure related to amino acid sequence and post-translational modifications including glycans; higher-order structure; primary biological properties mediated by target and receptor binding; product-related substances and impurities; host-cell impurities; general properties of the finished drug product, including strength and formulation; subvisible and submicron particles and aggregates; and forced thermal degradation. ABP 501 had the same amino acid sequence and similar post-translational modification profiles compared with adalimumab RPs. Primary structure, higher-order structure, and biological activities were similar for the three products. Product-related size and charge variants and aggregate and particle levels were also similar. ABP 501 had very low residual host-cell protein and DNA. The finished ABP 501 drug product has the same strength with regard to protein concentration and fill volume as adalimumab RPs. ABP 501 and the RPs had a similar stability profile both in normal storage and thermal stress conditions. Based on the comprehensive analytical similarity assessment, ABP 501 was found to be similar to adalimumab with respect to physicochemical and biological properties.

  10. RNA-TVcurve: a Web server for RNA secondary structure comparison based on a multi-scale similarity of its triple vector curve representation.

    Science.gov (United States)

    Li, Ying; Shi, Xiaohu; Liang, Yanchun; Xie, Juan; Zhang, Yu; Ma, Qin

    2017-01-21

    RNAs have been found to carry diverse functionalities in nature. Inferring the similarity between two given RNAs is a fundamental step to understand and interpret their functional relationship. The majority of functional RNAs show conserved secondary structures, rather than sequence conservation. Those algorithms relying on sequence-based features usually have limitations in their prediction performance. Hence, integrating RNA structure features is very critical for RNA analysis. Existing algorithms mainly fall into two categories: alignment-based and alignment-free. The alignment-free algorithms of RNA comparison usually have lower time complexity than alignment-based algorithms. An alignment-free RNA comparison algorithm was proposed, in which novel numerical representations RNA-TVcurve (triple vector curve representation) of RNA sequence and corresponding secondary structure features are provided. Then a multi-scale similarity score of two given RNAs was designed based on wavelet decomposition of their numerical representation. In support of RNA mutation and phylogenetic analysis, a web server (RNA-TVcurve) was designed based on this alignment-free RNA comparison algorithm. It provides three functional modules: 1) visualization of numerical representation of RNA secondary structure; 2) detection of single-point mutation based on secondary structure; and 3) comparison of pairwise and multiple RNA secondary structures. The inputs of the web server require RNA primary sequences, while corresponding secondary structures are optional. For the primary sequences alone, the web server can compute the secondary structures using free energy minimization algorithm in terms of RNAfold tool from Vienna RNA package. RNA-TVcurve is the first integrated web server, based on an alignment-free method, to deliver a suite of RNA analysis functions, including visualization, mutation analysis and multiple RNAs structure comparison. The comparison results with two popular RNA

  11. Estimating correlation and covariance matrices by weighting of market similarity

    OpenAIRE

    Michael C. M\\"unnix; Rudi Sch\\"afer; Oliver Grothe

    2010-01-01

    We discuss a weighted estimation of correlation and covariance matrices from historical financial data. To this end, we introduce a weighting scheme that accounts for similarity of previous market conditions to the present one. The resulting estimators are less biased and show lower variance than either unweighted or exponentially weighted estimators. The weighting scheme is based on a similarity measure which compares the current correlation structure of the market to the structures at past ...

  12. Isoforms of thyroxine-binding globulin as a model for molecular epidemiology of human cancer risk

    International Nuclear Information System (INIS)

    Golovaty, A.S.; Lapko, A.G.

    2000-01-01

    -binding globulin (TBG) by 50-60%, but no elevation in free T4, as compared with similar control groups of from Minsk. One of the reasons for the euthyroid syndrome in teenagers from the contaminated region was shown to be the blood isoforms in TBG. These isoforms differed in the structure of the carbohydrate components and as a rule are characterized by a prolonged circulation time. Using specific affinity chromatography, with subsequent immunological assay we shown that a certain amount of serum TBG-molecules in persons from Khojniki contains a high level of TBG (about 30% higher than the control group) containing fucosyalated biantennary sugar chains with more prolonged survival time. Previous findings showed that increased levels of fucosylation are observed for some serum glycoproteins in the blood of tumour patients. We provide evidence for variations in the TBGfuc which are contained in the serum TBG pool of patients suffering from cancer with various localisation. Thus, analysis of TBGfuc may be regarded as a prognostic marker in the determination of risk groups. The molecular mechanism of increased activity of fucosyl transferases will be discussed. We propose to measure the level of TBG fucosylated to assess the human cancer risk and habitants of contaminated region of Belarus. (authors)

  13. Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.

    Directory of Open Access Journals (Sweden)

    Gareth W Morgan

    2010-02-01

    Full Text Available Vaccinia virus (VACV uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC, a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs. Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD motif, which is conserved in the kinesin-1-binding sequence (KBS of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.

  14. A hybrid algorithm for selecting head-related transfer function based on similarity of anthropometric structures

    Science.gov (United States)

    Zeng, Xiang-Yang; Wang, Shu-Guang; Gao, Li-Ping

    2010-09-01

    As the basic data for virtual auditory technology, head-related transfer function (HRTF) has many applications in the areas of room acoustic modeling, spatial hearing and multimedia. How to individualize HRTF fast and effectively has become an opening problem at present. Based on the similarity and relativity of anthropometric structures, a hybrid HRTF customization algorithm, which has combined the method of principal component analysis (PCA), multiple linear regression (MLR) and database matching (DM), has been presented in this paper. The HRTFs selected by both the best match and the worst match have been applied into obtaining binaurally auralized sounds, which are then used for subjective listening experiments and the results are compared. For the area in the horizontal plane, the localization results have shown that the selection of HRTFs can enhance the localization accuracy and can also abate the problem of front-back confusion.

  15. Multidimensional Riemann problem with self-similar internal structure - part III - a multidimensional analogue of the HLLI Riemann solver for conservative hyperbolic systems

    Science.gov (United States)

    Balsara, Dinshaw S.; Nkonga, Boniface

    2017-10-01

    Just as the quality of a one-dimensional approximate Riemann solver is improved by the inclusion of internal sub-structure, the quality of a multidimensional Riemann solver is also similarly improved. Such multidimensional Riemann problems arise when multiple states come together at the vertex of a mesh. The interaction of the resulting one-dimensional Riemann problems gives rise to a strongly-interacting state. We wish to endow this strongly-interacting state with physically-motivated sub-structure. The fastest way of endowing such sub-structure consists of making a multidimensional extension of the HLLI Riemann solver for hyperbolic conservation laws. Presenting such a multidimensional analogue of the HLLI Riemann solver with linear sub-structure for use on structured meshes is the goal of this work. The multidimensional MuSIC Riemann solver documented here is universal in the sense that it can be applied to any hyperbolic conservation law. The multidimensional Riemann solver is made to be consistent with constraints that emerge naturally from the Galerkin projection of the self-similar states within the wave model. When the full eigenstructure in both directions is used in the present Riemann solver, it becomes a complete Riemann solver in a multidimensional sense. I.e., all the intermediate waves are represented in the multidimensional wave model. The work also presents, for the very first time, an important analysis of the dissipation characteristics of multidimensional Riemann solvers. The present Riemann solver results in the most efficient implementation of a multidimensional Riemann solver with sub-structure. Because it preserves stationary linearly degenerate waves, it might also help with well-balancing. Implementation-related details are presented in pointwise fashion for the one-dimensional HLLI Riemann solver as well as the multidimensional MuSIC Riemann solver.

  16. Self-Similarity of Plasmon Edge Modes on Koch Fractal Antennas.

    Science.gov (United States)

    Bellido, Edson P; Bernasconi, Gabriel D; Rossouw, David; Butet, Jérémy; Martin, Olivier J F; Botton, Gianluigi A

    2017-11-28

    We investigate the plasmonic behavior of Koch snowflake fractal geometries and their possible application as broadband optical antennas. Lithographically defined planar silver Koch fractal antennas were fabricated and characterized with high spatial and spectral resolution using electron energy loss spectroscopy. The experimental data are supported by numerical calculations carried out with a surface integral equation method. Multiple surface plasmon edge modes supported by the fractal structures have been imaged and analyzed. Furthermore, by isolating and reproducing self-similar features in long silver strip antennas, the edge modes present in the Koch snowflake fractals are identified. We demonstrate that the fractal response can be obtained by the sum of basic self-similar segments called characteristic edge units. Interestingly, the plasmon edge modes follow a fractal-scaling rule that depends on these self-similar segments formed in the structure after a fractal iteration. As the size of a fractal structure is reduced, coupling of the modes in the characteristic edge units becomes relevant, and the symmetry of the fractal affects the formation of hybrid modes. This analysis can be utilized not only to understand the edge modes in other planar structures but also in the design and fabrication of fractal structures for nanophotonic applications.

  17. Perception of similarity: a model for social network dynamics

    International Nuclear Information System (INIS)

    Javarone, Marco Alberto; Armano, Giuliano

    2013-01-01

    Some properties of social networks (e.g., the mixing patterns and the community structure) appear deeply influenced by the individual perception of people. In this work we map behaviors by considering similarity and popularity of people, also assuming that each person has his/her proper perception and interpretation of similarity. Although investigated in different ways (depending on the specific scientific framework), from a computational perspective similarity is typically calculated as a distance measure. In accordance with this view, to represent social network dynamics we developed an agent-based model on top of a hyperbolic space on which individual distance measures are calculated. Simulations, performed in accordance with the proposed model, generate small-world networks that exhibit a community structure. We deem this model to be valuable for analyzing the relevant properties of real social networks. (paper)

  18. Clustering biomolecular complexes by residue contacts similarity

    NARCIS (Netherlands)

    Garcia Lopes Maia Rodrigues, João; Trellet, Mikaël; Schmitz, Christophe; Kastritis, Panagiotis; Karaca, Ezgi; Melquiond, Adrien S J; Bonvin, Alexandre M J J; Garcia Lopes Maia Rodrigues, João

    Inaccuracies in computational molecular modeling methods are often counterweighed by brute-force generation of a plethora of putative solutions. These are then typically sieved via structural clustering based on similarity measures such as the root mean square deviation (RMSD) of atomic positions.

  19. User recommendation in healthcare social media by assessing user similarity in heterogeneous network.

    Science.gov (United States)

    Jiang, Ling; Yang, Christopher C

    2017-09-01

    The rapid growth of online health social websites has captured a vast amount of healthcare information and made the information easy to access for health consumers. E-patients often use these social websites for informational and emotional support. However, health consumers could be easily overwhelmed by the overloaded information. Healthcare information searching can be very difficult for consumers, not to mention most of them are not skilled information searcher. In this work, we investigate the approaches for measuring user similarity in online health social websites. By recommending similar users to consumers, we can help them to seek informational and emotional support in a more efficient way. We propose to represent the healthcare social media data as a heterogeneous healthcare information network and introduce the local and global structural approaches for measuring user similarity in a heterogeneous network. We compare the proposed structural approaches with the content-based approach. Experiments were conducted on a dataset collected from a popular online health social website, and the results showed that content-based approach performed better for inactive users, while structural approaches performed better for active users. Moreover, global structural approach outperformed local structural approach for all user groups. In addition, we conducted experiments on local and global structural approaches using different weight schemas for the edges in the network. Leverage performed the best for both local and global approaches. Finally, we integrated different approaches and demonstrated that hybrid method yielded better performance than the individual approach. The results indicate that content-based methods can effectively capture the similarity of inactive users who usually have focused interests, while structural methods can achieve better performance when rich structural information is available. Local structural approach only considers direct connections

  20. BSSF: a fingerprint based ultrafast binding site similarity search and function analysis server

    Directory of Open Access Journals (Sweden)

    Jiang Hualiang

    2010-01-01

    Full Text Available Abstract Background Genome sequencing and post-genomics projects such as structural genomics are extending the frontier of the study of sequence-structure-function relationship of genes and their products. Although many sequence/structure-based methods have been devised with the aim of deciphering this delicate relationship, there still remain large gaps in this fundamental problem, which continuously drives researchers to develop novel methods to extract relevant information from sequences and structures and to infer the functions of newly identified genes by genomics technology. Results Here we present an ultrafast method, named BSSF(Binding Site Similarity & Function, which enables researchers to conduct similarity searches in a comprehensive three-dimensional binding site database extracted from PDB structures. This method utilizes a fingerprint representation of the binding site and a validated statistical Z-score function scheme to judge the similarity between the query and database items, even if their similarities are only constrained in a sub-pocket. This fingerprint based similarity measurement was also validated on a known binding site dataset by comparing with geometric hashing, which is a standard 3D similarity method. The comparison clearly demonstrated the utility of this ultrafast method. After conducting the database searching, the hit list is further analyzed to provide basic statistical information about the occurrences of Gene Ontology terms and Enzyme Commission numbers, which may benefit researchers by helping them to design further experiments to study the query proteins. Conclusions This ultrafast web-based system will not only help researchers interested in drug design and structural genomics to identify similar binding sites, but also assist them by providing further analysis of hit list from database searching.

  1. Zooplankton structure in two interconnected ponds: similarities and differences

    Directory of Open Access Journals (Sweden)

    Špoljar Maria

    2016-03-01

    Full Text Available The research of zooplankton diversity, abundance and trophic structure was conducted during the summer period in pelagial zone on the longitudinal profile of the Sutla River Backwater. Investigated site consists of two interconnected basins: transparent Upper Basin with submerged macrophytes and turbid Lower Basin without macrophytes in the littoral zone. In the Upper Basin, abundance and diversity of zooplankton in the pelagial was higher in comparison to the Lower Basin, with prevailing species of genus Keratella as microfilter-feeder, and genera of Polyartha and Trihocerca as macrofilter-feeder rotifers. On the contrary, in the Lower Basin, crustaceans dominated in abundance. Microfilter-feeder cladoceran (Bosmina longirostris and larval and adult stages of macrofilter-feeder copepod (Macrocyclops albidus prevailed in the Lower Basin. Fish predation pressure was more pronounced in the pelagial of the Upper Basin, indicated by low cladoceran abundance in the surface layer. Although the studied basins were interconnected, results indicate significant (Mann-Whitney U test, p < 0.05 differences in the zooplankton structure as a potential result of the macrophyte impact on environmental conditions and fish predation pressure.

  2. The Hofmethode: Computing Semantic Similarities between E-Learning Products

    Directory of Open Access Journals (Sweden)

    Oliver Michel

    2009-11-01

    Full Text Available The key task in building useful e-learning repositories is to develop a system with an algorithm allowing users to retrieve information that corresponds to their specific requirements. To achieve this, products (or their verbal descriptions, i.e. presented in metadata need to be compared and structured according to the results of this comparison. Such structuring is crucial insofar as there are many search results that correspond to the entered keyword. The Hofmethode is an algorithm (based on psychological considerations to compute semantic similarities between texts and therefore offer a way to compare e-learning products. The computed similarity values are used to build semantic maps in which the products are visually arranged according to their similarities. The paper describes how the Hofmethode is implemented in the online database edulap, and how it contributes to help the user to explore the data in which he is interested.

  3. Structural similarities and functional differences clarify evolutionary relationships between tRNA healing enzymes and the myelin enzyme CNPase.

    Science.gov (United States)

    Muruganandam, Gopinath; Raasakka, Arne; Myllykoski, Matti; Kursula, Inari; Kursula, Petri

    2017-05-16

    Eukaryotic tRNA splicing is an essential process in the transformation of a primary tRNA transcript into a mature functional tRNA molecule. 5'-phosphate ligation involves two steps: a healing reaction catalyzed by polynucleotide kinase (PNK) in association with cyclic phosphodiesterase (CPDase), and a sealing reaction catalyzed by an RNA ligase. The enzymes that catalyze tRNA healing in yeast and higher eukaryotes are homologous to the members of the 2H phosphoesterase superfamily, in particular to the vertebrate myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). We employed different biophysical and biochemical methods to elucidate the overall structural and functional features of the tRNA healing enzymes yeast Trl1 PNK/CPDase and lancelet PNK/CPDase and compared them with vertebrate CNPase. The yeast and the lancelet enzymes have cyclic phosphodiesterase and polynucleotide kinase activity, while vertebrate CNPase lacks PNK activity. In addition, we also show that the healing enzymes are structurally similar to the vertebrate CNPase by applying synchrotron radiation circular dichroism spectroscopy and small-angle X-ray scattering. We provide a structural analysis of the tRNA healing enzyme PNK and CPDase domains together. Our results support evolution of vertebrate CNPase from tRNA healing enzymes with a loss of function at its N-terminal PNK-like domain.

  4. BRSCW Reference Set Application: Karen Abbott -University of Arkansas (2014) — EDRN Public Portal

    Science.gov (United States)

    Our earlier glycoproteomic studies have identified bisecting glycoslyation and core fucosylation changes on particular glycoproteins in endometrioid ovarian cancer tissues and plasma (Abbott et al, 2010, Proteomics). We have validated that these glycan changes occur on the same glycoproteins in serous ovarian cancer plasma using a lectin-pull down western blot assays. We would like to used pooled reference samples to develop a sensitive magnetic bead-based assay to detect these glycoproteins with bisecting and core fucosylation changes.

  5. Observations and analysis of self-similar branching topology in glacier networks

    Science.gov (United States)

    Bahr, D.B.; Peckham, S.D.

    1996-01-01

    Glaciers, like rivers, have a branching structure which can be characterized by topological trees or networks. Probability distributions of various topological quantities in the networks are shown to satisfy the criterion for self-similarity, a symmetry structure which might be used to simplify future models of glacier dynamics. Two analytical methods of describing river networks, Shreve's random topology model and deterministic self-similar trees, are applied to the six glaciers of south central Alaska studied in this analysis. Self-similar trees capture the topological behavior observed for all of the glaciers, and most of the networks are also reasonably approximated by Shreve's theory. Copyright 1996 by the American Geophysical Union.

  6. Discrimination and Measurements of Three Flavonols with Similar Structure Using Terahertz Spectroscopy and Chemometrics

    Science.gov (United States)

    Yan, Ling; Liu, Changhong; Qu, Hao; Liu, Wei; Zhang, Yan; Yang, Jianbo; Zheng, Lei

    2018-03-01

    Terahertz (THz) technique, a recently developed spectral method, has been researched and used for the rapid discrimination and measurements of food compositions due to its low-energy and non-ionizing characteristics. In this study, THz spectroscopy combined with chemometrics has been utilized for qualitative and quantitative analysis of myricetin, quercetin, and kaempferol with concentrations of 0.025, 0.05, and 0.1 mg/mL. The qualitative discrimination was achieved by KNN, ELM, and RF models with the spectra pre-treatments. An excellent discrimination (100% CCR in the prediction set) could be achieved using the RF model. Furthermore, the quantitative analyses were performed by partial least square regression (PLSR) and least squares support vector machine (LS-SVM). Comparing to the PLSR models, the LS-SVM yielded better results with low RMSEP (0.0044, 0.0039, and 0.0048), higher Rp (0.9601, 0.9688, and 0.9359), and higher RPD (8.6272, 9.6333, and 7.9083) for myricetin, quercetin, and kaempferol, respectively. Our results demonstrate that THz spectroscopy technique is a powerful tool for identification of three flavonols with similar chemical structures and quantitative determination of their concentrations.

  7. A Signal Processing Method to Explore Similarity in Protein Flexibility

    Directory of Open Access Journals (Sweden)

    Simina Vasilache

    2010-01-01

    Full Text Available Understanding mechanisms of protein flexibility is of great importance to structural biology. The ability to detect similarities between proteins and their patterns is vital in discovering new information about unknown protein functions. A Distance Constraint Model (DCM provides a means to generate a variety of flexibility measures based on a given protein structure. Although information about mechanical properties of flexibility is critical for understanding protein function for a given protein, the question of whether certain characteristics are shared across homologous proteins is difficult to assess. For a proper assessment, a quantified measure of similarity is necessary. This paper begins to explore image processing techniques to quantify similarities in signals and images that characterize protein flexibility. The dataset considered here consists of three different families of proteins, with three proteins in each family. The similarities and differences found within flexibility measures across homologous proteins do not align with sequence-based evolutionary methods.

  8. Unsupervised Word Mapping Using Structural Similarities in Monolingual Embeddings

    OpenAIRE

    Aldarmaki, Hanan; Mohan, Mahesh; Diab, Mona

    2017-01-01

    Most existing methods for automatic bilingual dictionary induction rely on prior alignments between the source and target languages, such as parallel corpora or seed dictionaries. For many language pairs, such supervised alignments are not readily available. We propose an unsupervised approach for learning a bilingual dictionary for a pair of languages given their independently-learned monolingual word embeddings. The proposed method exploits local and global structures in monolingual vector ...

  9. The centroidal algorithm in molecular similarity and diversity calculations on confidential datasets

    Science.gov (United States)

    Trepalin, Sergey; Osadchiy, Nikolay

    2005-09-01

    Chemical structure provides exhaustive description of a compound, but it is often proprietary and thus an impediment in the exchange of information. For example, structure disclosure is often needed for the selection of most similar or dissimilar compounds. Authors propose a centroidal algorithm based on structural fragments (screens) that can be efficiently used for the similarity and diversity selections without disclosing structures from the reference set. For an increased security purposes, authors recommend that such set contains at least some tens of structures. Analysis of reverse engineering feasibility showed that the problem difficulty grows with decrease of the screen's radius. The algorithm is illustrated with concrete calculations on known steroidal, quinoline, and quinazoline drugs. We also investigate a problem of scaffold identification in combinatorial library dataset. The results show that relatively small screens of radius equal to 2 bond lengths perform well in the similarity sorting, while radius 4 screens yield better results in diversity sorting. The software implementation of the algorithm taking SDF file with a reference set generates screens of various radii which are subsequently used for the similarity and diversity sorting of external SDFs. Since the reverse engineering of the reference set molecules from their screens has the same difficulty as the RSA asymmetric encryption algorithm, generated screens can be stored openly without further encryption. This approach ensures an end user transfers only a set of structural fragments and no other data. Like other algorithms of encryption, the centroid algorithm cannot give 100% guarantee of protecting a chemical structure from dataset, but probability of initial structure identification is very small-order of 10-40 in typical cases.

  10. Understanding similarity of groundwater systems with empirical copulas

    Science.gov (United States)

    Haaf, Ezra; Kumar, Rohini; Samaniego, Luis; Barthel, Roland

    2016-04-01

    Within the classification framework for groundwater systems that aims for identifying similarity of hydrogeological systems and transferring information from a well-observed to an ungauged system (Haaf and Barthel, 2015; Haaf and Barthel, 2016), we propose a copula-based method for describing groundwater-systems similarity. Copulas are an emerging method in hydrological sciences that make it possible to model the dependence structure of two groundwater level time series, independently of the effects of their marginal distributions. This study is based on Samaniego et al. (2010), which described an approach calculating dissimilarity measures from bivariate empirical copula densities of streamflow time series. Subsequently, streamflow is predicted in ungauged basins by transferring properties from similar catchments. The proposed approach is innovative because copula-based similarity has not yet been applied to groundwater systems. Here we estimate the pairwise dependence structure of 600 wells in Southern Germany using 10 years of weekly groundwater level observations. Based on these empirical copulas, dissimilarity measures are estimated, such as the copula's lower- and upper corner cumulated probability, copula-based Spearman's rank correlation - as proposed by Samaniego et al. (2010). For the characterization of groundwater systems, copula-based metrics are compared with dissimilarities obtained from precipitation signals corresponding to the presumed area of influence of each groundwater well. This promising approach provides a new tool for advancing similarity-based classification of groundwater system dynamics. Haaf, E., Barthel, R., 2015. Methods for assessing hydrogeological similarity and for classification of groundwater systems on the regional scale, EGU General Assembly 2015, Vienna, Austria. Haaf, E., Barthel, R., 2016. An approach for classification of hydrogeological systems at the regional scale based on groundwater hydrographs EGU General Assembly

  11. Detecting groups of similar components in complex networks

    International Nuclear Information System (INIS)

    Wang Jiao; Lai, C-H

    2008-01-01

    We study how to detect groups in a complex network each of which consists of component nodes sharing a similar connection pattern. Based on the mixture models and the exploratory analysis set up by Newman and Leicht (2007 Proc. Natl. Acad. Sci. USA 104 9564), we develop an algorithm that is applicable to a network with any degree distribution. The partition of a network suggested by this algorithm also applies to its complementary network. In general, groups of similar components are not necessarily identical with the communities in a community network; thus partitioning a network into groups of similar components provides additional information of the network structure. The proposed algorithm can also be used for community detection when the groups and the communities overlap. By introducing a tunable parameter that controls the involved effects of the heterogeneity, we can also investigate conveniently how the group structure can be coupled with the heterogeneity characteristics. In particular, an interesting example shows a group partition can evolve into a community partition in some situations when the involved heterogeneity effects are tuned. The extension of this algorithm to weighted networks is discussed as well.

  12. Using sequence similarity networks for visualization of relationships across diverse protein superfamilies.

    Directory of Open Access Journals (Sweden)

    Holly J Atkinson

    Full Text Available The dramatic increase in heterogeneous types of biological data--in particular, the abundance of new protein sequences--requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity--GPCRs and kinases from humans, and the crotonase superfamily of enzymes--we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships.

  13. Using sequence similarity networks for visualization of relationships across diverse protein superfamilies.

    Science.gov (United States)

    Atkinson, Holly J; Morris, John H; Ferrin, Thomas E; Babbitt, Patricia C

    2009-01-01

    The dramatic increase in heterogeneous types of biological data--in particular, the abundance of new protein sequences--requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity--GPCRs and kinases from humans, and the crotonase superfamily of enzymes--we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships.

  14. Mutations in HNF1A result in marked alterations of plasma glycan profile

    DEFF Research Database (Denmark)

    Thanabalasingham, Gaya; Huffman, Jennifer E; Kattla, Jayesh J

    2013-01-01

    A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma...... proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated...... to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167...

  15. STRUCTURE OF MAIN ARBOREAL SPECIES IN CRUCE CABALLERO PARK AND ITS FLORISTIC SIMILARITY WITH AREAS FROM ARGENTINE AND BRAZIL

    Directory of Open Access Journals (Sweden)

    Román Carlos Ríos

    2010-08-01

    Full Text Available The present work aimed to study the fitossociologic structure and floristic similarity among seasonal and mixed forests of Argentina and Brazil. Cruce Caballero Park with 522 hectares where the method of multiple plots was adopted with (20 x 10 m. In each plot all individual tree of size equal or heigher than 5 cm diameter were registered, being measured the stem diameter and height into three environmental compartments, Haplorthox, Ustorthent and Udorthent. In Haplorthox, Araucaria angustifolia (Bertol. Kuntze prevail at higher stratum and Sorocea bonplandii (Baill. W.C.Burger, Lanj. & Boer, Cabralea canjerana (Vell. Mart., Ocotea lancifolia Mez and Apuleia leiocarpa J.F.Macbr. follow it. In Ustorthent araucaria is absent and Gymnanthes concolor Müll.Arg., Trichilia claussenii C.DC., Apuleia leiocarpa, Pilocarpus pennatifolius Lem. and Sorocea bonplandii prevail. Aracuaria is scarce in Udorthent where Parapiptadenia rigida (Benth. Brenan, Alchornea triplinervia Müll.Arg., Luehea divaricata Mart., Erythrina falcata Benth. and Myrsine gardneriana A.DC. prevail. A comparative analysis shown Cruce Caballero more similar to seasonal forests than mixed araucaria forest from Brazil.

  16. Detection of structurally similar adulterants in botanical dietary supplements by thin-layer chromatography and surface enhanced Raman spectroscopy combined with two-dimensional correlation spectroscopy.

    Science.gov (United States)

    Li, Hao; Zhu, Qing xia; Chwee, Tsz sian; Wu, Lin; Chai, Yi feng; Lu, Feng; Yuan, Yong fang

    2015-07-09

    Thin-layer chromatography (TLC) coupled with surface enhanced Raman spectroscopy (SERS) has been widely used for the study of various complex systems, especially for the detection of adulterants in botanical dietary supplements (BDS). However, this method is not sufficient to distinguish structurally similar adulterants in BDS since the analogs have highly similar chromatographic and/or spectroscopic behaviors. Taking into account the fact that higher cost and more time will be required for comprehensive chromatographic separation, more efforts with respect to spectroscopy are now focused on analyzing the overlapped SERS peaks. In this paper, the combination of a TLC-SERS method with two-dimensional correlation spectroscopy (2DCOS), with duration of exposure to laser as the perturbation, is applied to solve this problem. Besides the usual advantages of the TLC-SERS method, such as its simplicity, rapidness, and sensitivity, more advantages are presented here, such as enhanced selectivity and good reproducibility, which are obtained by 2DCOS. Two chemicals with similar structures are successfully differentiated from the complex BDS matrices. The study provides a more accurate qualitative screening method for detection of BDS with adulterants, and offers a new universal approach for the analysis of highly overlapped SERS peaks. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. The growth of vegetative and reproductive structures (leaves and silks) respond similarly to hydraulic cues in maize.

    Science.gov (United States)

    Turc, Olivier; Bouteillé, Marie; Fuad-Hassan, Avan; Welcker, Claude; Tardieu, François

    2016-10-01

    The elongation of styles and stigma (silks) of maize (Zea mays) flowers is rapid (1-3 mm h(-1) ), occurs over a short period and plays a pivotal role in reproductive success in adverse environments. Silk elongation rate was measured using displacement transducers in 350 plants of eight genotypes during eight experiments with varying evaporative demand and soil water status. Measured time courses revealed that silk elongation rate closely followed changes in soil water status and evaporative demand, with day-night alternations similar to those in leaves. Day-night alternations were steeper with high than with low plant transpiration rate, manipulated via evaporative demand or by covering part of the leaf area. Half times of changes in silk elongation rate upon changes in evaporative demand or soil water status were 10-30 min, similar to those in leaves. The sensitivity of silk elongation rate to xylem water potential was genetically linked to that of leaf elongation rate. Lines greatly differed for these sensitivities. These results are consistent with a common hydraulic control of expansive growth in vegetative and reproductive structures upon changes in environmental conditions via a close connection with the xylem water potential. They have important implications for breeding, modelling and phenotyping. © 2016 INRA. New Phytologist © 2016 New Phytologist Trust.

  18. Synthesis of Human Milk Oligosaccharides and Regioselective Ring Opening of Oxabicycles

    DEFF Research Database (Denmark)

    Jennum, Camilla Arboe

    . The tetrasaccharides were formed both by sequential and the developed one-pot method. Deprotection of the protecting group at the C-2-position on the galactose moiety liberated an acceptor for the fucosylation eventually creating the two linear pentasaccharides Lacto-N-fucopentaose I and Lacto-N-neofucopentaose I...... ligands. The ring opened iii products were similar to compounds, which had shown to be potential protein Bcl-XL antagonists, a target for future drugs in cancer treatment. The aim was to create a general asymmetric ring opening method of several enantiopure oxabicycles having different functional moieties...

  19. Coupling effect of nodes popularity and similarity on social network persistence.

    Science.gov (United States)

    Jin, Xiaogang; Jin, Cheng; Huang, Jiaxuan; Min, Yong

    2017-02-21

    Network robustness represents the ability of networks to withstand failures and perturbations. In social networks, maintenance of individual activities, also called persistence, is significant towards understanding robustness. Previous works usually consider persistence on pre-generated network structures; while in social networks, the network structure is growing with the cascading inactivity of existed individuals. Here, we address this challenge through analysis for nodes under a coevolution model, which characterizes individual activity changes under three network growth modes: following the descending order of nodes' popularity, similarity or uniform random. We show that when nodes possess high spontaneous activities, a popularity-first growth mode obtains highly persistent networks; otherwise, with low spontaneous activities, a similarity-first mode does better. Moreover, a compound growth mode, with the consecutive joining of similar nodes in a short period and mixing a few high popularity nodes, obtains the highest persistence. Therefore, nodes similarity is essential for persistent social networks, while properly coupling popularity with similarity further optimizes the persistence. This demonstrates the evolution of nodes activity not only depends on network topology, but also their connective typology.

  20. Relativistic quantum similarities in atoms in position and momentum spaces

    International Nuclear Information System (INIS)

    Maldonado, P.; Sarsa, A.; Buendia, E.; Galvez, F.J.

    2011-01-01

    A study of different quantum similarity measures and their corresponding quantum similarity indices is carried out for the atoms from H to Lr (Z=1-103). Relativistic effects in both position and momentum spaces have been studied by comparing the relativistic values to the non-relativistic ones. We have used the atomic electron density in both position and momentum spaces obtained within relativistic and non-relativistic numerical-parameterized optimized effective potential approximations. -- Highlights: → Quantum similarity measures and indices in electronic structure of atoms. → Position and momentum electronic densities. → Similarity of relativistic and non-relativistic densities. → Similarity of core and valence regions of different atoms. → Dependence with Z along the Periodic Table.

  1. Textual and chemical information processing: different domains but similar algorithms

    Directory of Open Access Journals (Sweden)

    Peter Willett

    2000-01-01

    Full Text Available This paper discusses the extent to which algorithms developed for the processing of textual databases are also applicable to the processing of chemical structure databases, and vice versa. Applications discussed include: an algorithm for distribution sorting that has been applied to the design of screening systems for rapid chemical substructure searching; the use of measures of inter-molecular structural similarity for the analysis of hypertext graphs; a genetic algorithm for calculating term weights for relevance feedback searching for determining whether a molecule is likely to exhibit biological activity; and the use of data fusion to combine the results of different chemical similarity searches.

  2. Cell surface carbohydrate changes during embryonic and fetal skin development

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Holbrook, K; Clausen, H

    1986-01-01

    Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N-acetyllac......Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N...

  3. Self-Similar Symmetry Model and Cosmic Microwave Background

    Directory of Open Access Journals (Sweden)

    Tomohide eSonoda

    2016-05-01

    Full Text Available In this paper, we present the self-similar symmetry (SSS model that describes the hierarchical structure of the universe. The model is based on the concept of self-similarity, which explains the symmetry of the cosmic microwave background (CMB. The approximate length and time scales of the six hierarchies of the universe---grand unification, electroweak unification, the atom, the pulsar, the solar system, and the galactic system---are derived from the SSS model. In addition, the model implies that the electron mass and gravitational constant could vary with the CMB radiation temperature.

  4. Learning Faster by Discovering and Exploiting Object Similarities

    Directory of Open Access Journals (Sweden)

    Tadej Janež

    2013-03-01

    Full Text Available In this paper we explore the question: “Is it possible to speed up the learning process of an autonomous agent by performing experiments in a more complex environment (i.e., an environment with a greater number of different objects?” To this end, we use a simple robotic domain, where the robot has to learn a qualitative model predicting the change in the robot's distance to an object. To quantify the environment's complexity, we defined cardinal complexity as the number of objects in the robot's world, and behavioural complexity as the number of objects' distinct behaviours. We propose Error reduction merging (ERM, a new learning method that automatically discovers similarities in the structure of the agent's environment. ERM identifies different types of objects solely from the data measured and merges the observations of objects that behave in the same or similar way in order to speed up the agent's learning. We performed a series of experiments in worlds of increasing complexity. The results in our simple domain indicate that ERM was capable of discovering structural similarities in the data which indeed made the learning faster, clearly superior to conventional learning. This observed trend occurred with various machine learning algorithms used inside the ERM method.

  5. Comparative mapping reveals similar linkage of functional genes to ...

    Indian Academy of Sciences (India)

    genes between O. sativa and B. napus may have consistent function and control similar traits, which may be ..... acea chromosomes reveals islands of conserved organization. ... 1998 Conserved structure and function of the Arabidopsis flow-.

  6. Structure of the clinical and geriatric depression: Similarities and differences

    Directory of Open Access Journals (Sweden)

    Novović Zdenka

    2006-01-01

    Full Text Available Studies demonstrating the uniqueness of depression in old age are numerous, but conclusions on the fact if the problems of the elderly people cause depression or if they are a part of depression are not unique. The aim of this paper is to compare the structure of depression of old people without the history of mental illness and middle-aged people treated for depression. The sample consists of 82 healthy inmates of different Homes for the Aged and 78 patients diagnosed with some sort of affective disorder. A depression has been assessed with the shorten version of the MMPI D-scale. The structure of the geriatric and clinical depression has been compared with the method of maximum likelihood, over the matrix of co-variances of answers on the items on the depression scale. The results point out to the statistically significant difference in the structure of depression of the old and clinically depressed individuals. However, half of the items of the D-scale have significant loadings on the factor of depression in both groups. The essence of the depression in both samples is made of cognitive subject matters, depressive affect, decline of motivation and a negative estimate of one's basic abilities. Symptoms concerning low self-esteem, experiencing cognitive deficit, energy and impaired physical health have been significant in describing the clinical depression, while a feeling of reduced positive stimulation and the affective liability is typical for the depression of geriatric sample. The conclusion is that, despite the differences, there is a common core of symptoms that makes the essence of depression, apart from the samples.

  7. Waveguiding and mirroring effects in stochastic self-similar and Cantorian ε(∞) universe

    International Nuclear Information System (INIS)

    Iovane, G.

    2005-01-01

    A waveguiding effect is considered with respect to the large scale structure of the Universe, where the structures formation appears as if it were a classically self-similar random process at all astrophysical scales. The result is that it seems we live in an El Naschie's ε (∞) Cantorian space-time, where gravitational lensing and waveguiding effects can explain the appearing Universe. In particular, we consider filamentary and planar large scale structures as possible refraction channels for electromagnetic radiation coming from cosmological structures. From this vision the Universe appears like a large self-similar adaptive mirrors set. Consequently, an infinite Universe is just an optical illusion that is produced by mirroring effects connected with the large scale structure of a finite and not so large Universe. Thanks to the presented analytical model supported by a numerical simulation, it is possible to explain the quasar luminosity distribution and the presence of 'twin' or 'brother' objects. More generally, the infinity and the abundance of astrophysical objects could be just a mirroring effect due to the peculiar self-similarity of the Universe

  8. Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab.

    Science.gov (United States)

    Velayudhan, Jyoti; Chen, Yuh-Feng; Rohrbach, Amanda; Pastula, Christina; Maher, Gwen; Thomas, Heather; Brown, Ryan; Born, Teresa L

    2016-08-01

    Due to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies (mAbs), differences in structure and function may be expected during development of biosimilar mAbs. Important regulatory requirements for approval of biosimilar products involve comprehensive assessments of any potential differences between proposed biosimilars and reference mAbs, including differences in all known mechanisms of action, using sensitive and relevant methods. Any identified structural differences should not result in differences in biofunctional or clinical activity. A comprehensive assessment comparing the Amgen biosimilar candidate ABP 501 with FDA-licensed adalimumab (adalimumab [US]) and EU-authorized adalimumab (adalimumab [EU]) was conducted to demonstrate similarity in biofunctional activity. The functional similarity assessment included testing of binding kinetics to soluble tumor necrosis factor α (TNFα) and relative binding to transmembrane TNFα. The neutralization of TNFα-induced caspase activation, TNFα- and lymphotoxin-α (LTα)-induced chemokine production, and cytotoxicity was also tested. Binding to Fc-gamma receptors FcγRIa, FcγRIIa (131H), FcγRIIIa (158V and 158F), and neonatal Fc receptor (FcRn) was compared with the reference mAbs, as was antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The data demonstrate that ABP 501 is similar to both adalimumab (US) and adalimumab (EU) with respect to evaluated biofunctional activities. Similarity in biofunctional activity is a critical component of the totality of evidence required for demonstration of biosimilarity. The functional similarity demonstrated for ABP 501 comprehensively assesses the known mechanisms of action of adalimumab, supporting the conclusion that ABP 501, adalimumab (US), and adalimumab (EU) are likely to be clinically similar.

  9. Statistical potential-based amino acid similarity matrices for aligning distantly related protein sequences.

    Science.gov (United States)

    Tan, Yen Hock; Huang, He; Kihara, Daisuke

    2006-08-15

    Aligning distantly related protein sequences is a long-standing problem in bioinformatics, and a key for successful protein structure prediction. Its importance is increasing recently in the context of structural genomics projects because more and more experimentally solved structures are available as templates for protein structure modeling. Toward this end, recent structure prediction methods employ profile-profile alignments, and various ways of aligning two profiles have been developed. More fundamentally, a better amino acid similarity matrix can improve a profile itself; thereby resulting in more accurate profile-profile alignments. Here we have developed novel amino acid similarity matrices from knowledge-based amino acid contact potentials. Contact potentials are used because the contact propensity to the other amino acids would be one of the most conserved features of each position of a protein structure. The derived amino acid similarity matrices are tested on benchmark alignments at three different levels, namely, the family, the superfamily, and the fold level. Compared to BLOSUM45 and the other existing matrices, the contact potential-based matrices perform comparably in the family level alignments, but clearly outperform in the fold level alignments. The contact potential-based matrices perform even better when suboptimal alignments are considered. Comparing the matrices themselves with each other revealed that the contact potential-based matrices are very different from BLOSUM45 and the other matrices, indicating that they are located in a different basin in the amino acid similarity matrix space.

  10. Calculating the knowledge-based similarity of functional groups using crystallographic data

    Science.gov (United States)

    Watson, Paul; Willett, Peter; Gillet, Valerie J.; Verdonk, Marcel L.

    2001-09-01

    A knowledge-based method for calculating the similarity of functional groups is described and validated. The method is based on experimental information derived from small molecule crystal structures. These data are used in the form of scatterplots that show the likelihood of a non-bonded interaction being formed between functional group A (the `central group') and functional group B (the `contact group' or `probe'). The scatterplots are converted into three-dimensional maps that show the propensity of the probe at different positions around the central group. Here we describe how to calculate the similarity of a pair of central groups based on these maps. The similarity method is validated using bioisosteric functional group pairs identified in the Bioster database and Relibase. The Bioster database is a critical compilation of thousands of bioisosteric molecule pairs, including drugs, enzyme inhibitors and agrochemicals. Relibase is an object-oriented database containing structural data about protein-ligand interactions. The distributions of the similarities of the bioisosteric functional group pairs are compared with similarities for all the possible pairs in IsoStar, and are found to be significantly different. Enrichment factors are also calculated showing the similarity method is statistically significantly better than random in predicting bioisosteric functional group pairs.

  11. Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens

    Directory of Open Access Journals (Sweden)

    Gomez Shawn M

    2010-04-01

    Full Text Available Abstract Background In the course of infection, viruses such as HIV-1 must enter a cell, travel to sites where they can hijack host machinery to transcribe their genes and translate their proteins, assemble, and then leave the cell again, all while evading the host immune system. Thus, successful infection depends on the pathogen's ability to manipulate the biological pathways and processes of the organism it infects. Interactions between HIV-encoded and human proteins provide one means by which HIV-1 can connect into cellular pathways to carry out these survival processes. Results We developed and applied a computational approach to predict interactions between HIV and human proteins based on structural similarity of 9 HIV-1 proteins to human proteins having known interactions. Using functional data from RNAi studies as a filter, we generated over 2000 interaction predictions between HIV proteins and 406 unique human proteins. Additional filtering based on Gene Ontology cellular component annotation reduced the number of predictions to 502 interactions involving 137 human proteins. We find numerous known interactions as well as novel interactions showing significant functional relevance based on supporting Gene Ontology and literature evidence. Conclusions Understanding the interplay between HIV-1 and its human host will help in understanding the viral lifecycle and the ways in which this virus is able to manipulate its host. The results shown here provide a potential set of interactions that are amenable to further experimental manipulation as well as potential targets for therapeutic intervention.

  12. Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl-peptidase IV.

    Science.gov (United States)

    Herlihy, Sarah E; Tang, Yu; Phillips, Jonathan E; Gomer, Richard H

    2017-03-01

    Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV-like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. © 2016 The Protein Society.

  13. Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

    Science.gov (United States)

    Herlihy, Sarah E.; Tang, Yu; Phillips, Jonathan E.

    2017-01-01

    Abstract Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV‐like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. PMID:28028841

  14. The Impact of Protein Structure and Sequence Similarity on the Accuracy of Machine-Learning Scoring Functions for Binding Affinity Prediction.

    Science.gov (United States)

    Li, Hongjian; Peng, Jiangjun; Leung, Yee; Leung, Kwong-Sak; Wong, Man-Hon; Lu, Gang; Ballester, Pedro J

    2018-03-14

    It has recently been claimed that the outstanding performance of machine-learning scoring functions (SFs) is exclusively due to the presence of training complexes with highly similar proteins to those in the test set. Here, we revisit this question using 24 similarity-based training sets, a widely used test set, and four SFs. Three of these SFs employ machine learning instead of the classical linear regression approach of the fourth SF (X-Score which has the best test set performance out of 16 classical SFs). We have found that random forest (RF)-based RF-Score-v3 outperforms X-Score even when 68% of the most similar proteins are removed from the training set. In addition, unlike X-Score, RF-Score-v3 is able to keep learning with an increasing training set size, becoming substantially more predictive than X-Score when the full 1105 complexes are used for training. These results show that machine-learning SFs owe a substantial part of their performance to training on complexes with dissimilar proteins to those in the test set, against what has been previously concluded using the same data. Given that a growing amount of structural and interaction data will be available from academic and industrial sources, this performance gap between machine-learning SFs and classical SFs is expected to enlarge in the future.

  15. Predicting the performance of fingerprint similarity searching.

    Science.gov (United States)

    Vogt, Martin; Bajorath, Jürgen

    2011-01-01

    Fingerprints are bit string representations of molecular structure that typically encode structural fragments, topological features, or pharmacophore patterns. Various fingerprint designs are utilized in virtual screening and their search performance essentially depends on three parameters: the nature of the fingerprint, the active compounds serving as reference molecules, and the composition of the screening database. It is of considerable interest and practical relevance to predict the performance of fingerprint similarity searching. A quantitative assessment of the potential that a fingerprint search might successfully retrieve active compounds, if available in the screening database, would substantially help to select the type of fingerprint most suitable for a given search problem. The method presented herein utilizes concepts from information theory to relate the fingerprint feature distributions of reference compounds to screening libraries. If these feature distributions do not sufficiently differ, active database compounds that are similar to reference molecules cannot be retrieved because they disappear in the "background." By quantifying the difference in feature distribution using the Kullback-Leibler divergence and relating the divergence to compound recovery rates obtained for different benchmark classes, fingerprint search performance can be quantitatively predicted.

  16. Geomfinder: a multi-feature identifier of similar three-dimensional protein patterns: a ligand-independent approach.

    Science.gov (United States)

    Núñez-Vivanco, Gabriel; Valdés-Jiménez, Alejandro; Besoaín, Felipe; Reyes-Parada, Miguel

    2016-01-01

    Since the structure of proteins is more conserved than the sequence, the identification of conserved three-dimensional (3D) patterns among a set of proteins, can be important for protein function prediction, protein clustering, drug discovery and the establishment of evolutionary relationships. Thus, several computational applications to identify, describe and compare 3D patterns (or motifs) have been developed. Often, these tools consider a 3D pattern as that described by the residues surrounding co-crystallized/docked ligands available from X-ray crystal structures or homology models. Nevertheless, many of the protein structures stored in public databases do not provide information about the location and characteristics of ligand binding sites and/or other important 3D patterns such as allosteric sites, enzyme-cofactor interaction motifs, etc. This makes necessary the development of new ligand-independent methods to search and compare 3D patterns in all available protein structures. Here we introduce Geomfinder, an intuitive, flexible, alignment-free and ligand-independent web server for detailed estimation of similarities between all pairs of 3D patterns detected in any two given protein structures. We used around 1100 protein structures to form pairs of proteins which were assessed with Geomfinder. In these analyses each protein was considered in only one pair (e.g. in a subset of 100 different proteins, 50 pairs of proteins can be defined). Thus: (a) Geomfinder detected identical pairs of 3D patterns in a series of monoamine oxidase-B structures, which corresponded to the effectively similar ligand binding sites at these proteins; (b) we identified structural similarities among pairs of protein structures which are targets of compounds such as acarbose, benzamidine, adenosine triphosphate and pyridoxal phosphate; these similar 3D patterns are not detected using sequence-based methods; (c) the detailed evaluation of three specific cases showed the versatility

  17. Self-similar transmission properties of aperiodic Cantor potentials in gapped graphene

    Science.gov (United States)

    Rodríguez-González, Rogelio; Rodríguez-Vargas, Isaac; Díaz-Guerrero, Dan Sidney; Gaggero-Sager, Luis Manuel

    2016-01-01

    We investigate the transmission properties of quasiperiodic or aperiodic structures based on graphene arranged according to the Cantor sequence. In particular, we have found self-similar behaviour in the transmission spectra, and most importantly, we have calculated the scalability of the spectra. To do this, we implement and propose scaling rules for each one of the fundamental parameters: generation number, height of the barriers and length of the system. With this in mind we have been able to reproduce the reference transmission spectrum, applying the appropriate scaling rule, by means of the scaled transmission spectrum. These scaling rules are valid for both normal and oblique incidence, and as far as we can see the basic ingredients to obtain self-similar characteristics are: relativistic Dirac electrons, a self-similar structure and the non-conservation of the pseudo-spin.

  18. Structural Characterization of a Thrombin-Aptamer Complex by High Resolution Native Top-Down Mass Spectrometry

    Science.gov (United States)

    Zhang, Jiang; Loo, Rachel R. Ogorzalek; Loo, Joseph A.

    2017-09-01

    Native mass spectrometry (MS) with electrospray ionization (ESI) has evolved as an invaluable tool for the characterization of intact native proteins and non-covalently bound protein complexes. Here we report the structural characterization by high resolution native top-down MS of human thrombin and its complex with the Bock thrombin binding aptamer (TBA), a 15-nucleotide DNA with high specificity and affinity for thrombin. Accurate mass measurements revealed that the predominant form of native human α-thrombin contains a glycosylation mass of 2205 Da, corresponding to a sialylated symmetric biantennary oligosaccharide structure without fucosylation. Native MS showed that thrombin and TBA predominantly form a 1:1 complex under near physiological conditions (pH 6.8, 200 mM NH4OAc), but the binding stoichiometry is influenced by the solution ionic strength. In 20 mM ammonium acetate solution, up to two TBAs were bound to thrombin, whereas increasing the solution ionic strength destabilized the thrombin-TBA complex and 1 M NH4OAc nearly completely dissociated the complex. This observation is consistent with the mediation of thrombin-aptamer binding through electrostatic interactions and it is further consistent with the human thrombin structure that contains two anion binding sites on the surface. Electron capture dissociation (ECD) top-down MS of the thrombin-TBA complex performed with a high resolution 15 Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer showed the primary binding site to be at exosite I located near the N-terminal sequence of the heavy chain, consistent with crystallographic data. High resolution native top-down MS is complementary to traditional structural biology methods for structurally characterizing native proteins and protein-DNA complexes. [Figure not available: see fulltext.

  19. Semantic similarity between ontologies at different scales

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qingpeng; Haglin, David J.

    2016-04-01

    In the past decade, existing and new knowledge and datasets has been encoded in different ontologies for semantic web and biomedical research. The size of ontologies is often very large in terms of number of concepts and relationships, which makes the analysis of ontologies and the represented knowledge graph computational and time consuming. As the ontologies of various semantic web and biomedical applications usually show explicit hierarchical structures, it is interesting to explore the trade-offs between ontological scales and preservation/precision of results when we analyze ontologies. This paper presents the first effort of examining the capability of this idea via studying the relationship between scaling biomedical ontologies at different levels and the semantic similarity values. We evaluate the semantic similarity between three Gene Ontology slims (Plant, Yeast, and Candida, among which the latter two belong to the same kingdom—Fungi) using four popular measures commonly applied to biomedical ontologies (Resnik, Lin, Jiang-Conrath, and SimRel). The results of this study demonstrate that with proper selection of scaling levels and similarity measures, we can significantly reduce the size of ontologies without losing substantial detail. In particular, the performance of Jiang-Conrath and Lin are more reliable and stable than that of the other two in this experiment, as proven by (a) consistently showing that Yeast and Candida are more similar (as compared to Plant) at different scales, and (b) small deviations of the similarity values after excluding a majority of nodes from several lower scales. This study provides a deeper understanding of the application of semantic similarity to biomedical ontologies, and shed light on how to choose appropriate semantic similarity measures for biomedical engineering.

  20. Determining the semantic similarities among Gene Ontology terms.

    Science.gov (United States)

    Taha, Kamal

    2013-05-01

    We present in this paper novel techniques that determine the semantic relationships among GeneOntology (GO) terms. We implemented these techniques in a prototype system called GoSE, which resides between user application and GO database. Given a set S of GO terms, GoSE would return another set S' of GO terms, where each term in S' is semantically related to each term in S. Most current research is focused on determining the semantic similarities among GO ontology terms based solely on their IDs and proximity to one another in the GO graph structure, while overlooking the contexts of the terms, which may lead to erroneous results. The context of a GO term T is the set of other terms, whose existence in the GO graph structure is dependent on T. We propose novel techniques that determine the contexts of terms based on the concept of existence dependency. We present a stack-based sort-merge algorithm employing these techniques for determining the semantic similarities among GO terms.We evaluated GoSE experimentally and compared it with three existing methods. The results of measuring the semantic similarities among genes in KEGG and Pfam pathways retrieved from the DBGET and Sanger Pfam databases, respectively, have shown that our method outperforms the other three methods in recall and precision.

  1. Structural similarity causes different category-effects depending on task characteristics

    DEFF Research Database (Denmark)

    Gerlach, Christian

    2001-01-01

    difference was found on easy object decision tasks. In experiment 2 an advantage for natural objects was found during object decisions performed under degraded viewing conditions (lateralized stimulus presentation). It is argued that these findings can be accounted for by assuming that natural objects...... it is in difficult object decision tasks). However, when viewing conditions are degraded and performance tends to depend on global shape information (carried by low spatial frequency components), natural objects may fare better than artefacts because the global shape of natural objects reveals more of their identity......It has been suggested that category-specific impairments for natural objects may reflect that natural objects are more globally visually similar than artefacts and therefore more difficult to recognize following brain damage [Aphasiology 13 (1992) 169]. This account has been challenged...

  2. Toxmatch-a new software tool to aid in the development and evaluation of chemically similar groups.

    Science.gov (United States)

    Patlewicz, G; Jeliazkova, N; Gallegos Saliner, A; Worth, A P

    2008-01-01

    Chemical similarity is a widely used concept in toxicology, and is based on the hypothesis that similar compounds should have similar biological activities. This forms the underlying basis for performing read-across, forming chemical groups and developing (Quantitative) Structure-Activity Relationships ((Q)SARs). Chemical similarity is often perceived as structural similarity but in fact there are a number of other approaches that can be used to assess similarity. A systematic similarity analysis usually comprises two main steps. Firstly the chemical structures to be compared need to be characterised in terms of relevant descriptors which encode their physicochemical, topological, geometrical and/or surface properties. A second step involves a quantitative comparison of those descriptors using similarity (or dissimilarity) indices. This work outlines the use of chemical similarity principles in the formation of endpoint specific chemical groupings. Examples are provided to illustrate the development and evaluation of chemical groupings using a new software application called Toxmatch that was recently commissioned by the European Chemicals Bureau (ECB), of the European Commission's Joint Research Centre. Insights from using this software are highlighted with specific focus on the prospective application of chemical groupings under the new chemicals legislation, REACH.

  3. Altered fucosyltransferase expression in the superior temporal gyrus of elderly patients with schizophrenia.

    Science.gov (United States)

    Mueller, Toni M; Yates, Stefani D; Haroutunian, Vahram; Meador-Woodruff, James H

    2017-04-01

    Glycosylation is a post-translational modification that is an essential element in cell signaling and neurodevelopmental pathway regulation. Glycan attachment can influence the tertiary structure and molecular interactions of glycosylated substrates, adding an additional layer of regulatory complexity to functional mechanisms underlying central cell biological processes. One type of enzyme-mediated glycan attachment, fucosylation, can mediate glycoprotein and glycolipid cell surface expression, trafficking, secretion, and quality control to modulate a variety of inter- and intracellular signaling cascades. Building on prior reports of glycosylation abnormalities and evidence of dysregulated glycosylation enzyme expression in schizophrenia, we examined the protein expression of 5 key fucose-modifying enzymes: GDP-fucose:protein O-fucosyltransferase 1 (POFUT1), GDP-fucose:protein O-fucosyltransferase 2 (POFUT2), fucosyltransferase 8 (FUT8), fucosyltransferase 11 (FUT11), and plasma α-l-fucosidase (FUCA2) in postmortem superior temporal gyrus of schizophrenia (N=16) and comparison (N=14) subjects. We also used the fucose binding protein, Aleuria aurantia lectin (AAL), to assess α-1,6-fucosylated N-glycoprotein abundance in the same subjects. In schizophrenia, we found increased expression of POFUT2, a fucosyltransferase uniquely responsible for O-fucosylation of thrombospondin-like repeat domains that is involved in a non-canonical endoplasmic reticulum quality control pathway. We also found decreased expression of FUT8 in schizophrenia. Given that FUT8 is the only α-1,6-fucosyltransferase expressed in mammals, the concurrent decrease in AAL binding in schizophrenia, particularly evident for N-glycoproteins in the ~52-58kDa and ~60-70kDa molecular mass ranges, likely reflects a consequence of abnormal FUT8 expression in the disorder. Dysregulated FUT8 and POFUT2 expression could potentially explain a variety of molecular abnormalities in schizophrenia. Copyright

  4. Efficient Similarity Search Using the Earth Mover's Distance for Large Multimedia Databases

    DEFF Research Database (Denmark)

    Assent, Ira; Wichterich, Marc; Meisen, Tobias

    2008-01-01

    Multimedia similarity search in large databases requires efficient query processing. The Earth mover's distance, introduced in computer vision, is successfully used as a similarity model in a number of small-scale applications. Its computational complexity hindered its adoption in large multimedia...... databases. We enable directly indexing the Earth mover's distance in structures such as the R-tree and the VA-file by providing the accurate 'MinDist' function to any bounding rectangle in the index. We exploit the computational structure of the new MinDist to derive a new lower bound for the EMD Min...

  5. Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation.

    Science.gov (United States)

    Liang, Yuh-Jin; Kuo, Huan-Hsien; Lin, Chi-Hung; Chen, Yen-Ying; Yang, Bei-Chia; Cheng, Yuan-Yuan; Yu, Alice L; Khoo, Kay-Hooi; Yu, John

    2010-12-28

    A systematic survey of expression profiles of glycosphingolipids (GSLs) in two hESC lines and their differentiated embryoid body (EB) outgrowth with three germ layers was carried out using immunofluorescence, flow cytometry, and MALDI-MS and MS/MS analyses. In addition to the well-known hESC-specific markers stage-specific embryonic antigen 3 (SSEA-3) and SSEA-4, we identified several globosides and lacto-series GSLs, previously unrevealed in hESCs, including Gb(4)Cer, Lc(4)Cer, fucosyl Lc(4)Cer, Globo H, and disialyl Gb(5)Cer. During hESC differentiation into EBs, MS analysis revealed a clear-cut switch in the core structures of GSLs from globo- and lacto- to ganglio-series, which was not as evident by immunostaining with antibodies against SSEA-3 and SSEA-4, owing to their cross-reactivities with various glycosphingolipids. Such a switch was attributable to altered expression of key glycosyltransferases (GTs) in the biosynthetic pathways by the up-regulation of ganglio-series-related GTs with simultaneous down-regulation of globo- and lacto-series-related GTs. Thus, these results provide insights into the unique stage-specific transition and mechanism for alterations of GSL core structures during hESC differentiation. In addition, unique glycan structures uncovered by MS analyses may serve as surface markers for further delineation of hESCs and help identify of their functional roles not only in hESCs but also in cancers.

  6. Contrasting ecosystem-effects of morphologically similar copepods.

    Directory of Open Access Journals (Sweden)

    Blake Matthews

    Full Text Available Organisms alter the biotic and abiotic conditions of ecosystems. They can modulate the availability of resources to other species (ecosystem engineering and shape selection pressures on other organisms (niche construction. Very little is known about how the engineering effects of organisms vary among and within species, and, as a result, the ecosystem consequences of species diversification and phenotypic evolution are poorly understood. Here, using a common gardening experiment, we test whether morphologically similar species and populations of Diaptomidae copepods (Leptodiaptomus ashlandi, Hesperodiaptomus franciscanus, Skistodiaptomus oregonensis have similar or different effects on the structure and function of freshwater ecosystems. We found that copepod species had contrasting effects on algal biomass, ammonium concentrations, and sedimentation rates, and that copepod populations had contrasting effects on prokaryote abundance, sedimentation rates, and gross primary productivity. The average size of ecosystem-effect contrasts between species was similar to those between populations, and was comparable to those between fish species and populations measured in previous common gardening experiments. Our results suggest that subtle morphological variation among and within species can cause multifarious and divergent ecosystem-effects. We conclude that using morphological trait variation to assess the functional similarity of organisms may underestimate the importance of species and population diversity for ecosystem functioning.

  7. Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

    Science.gov (United States)

    Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

    2011-01-01

    Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

  8. Virtual drug screen schema based on multiview similarity integration and ranking aggregation.

    Science.gov (United States)

    Kang, Hong; Sheng, Zhen; Zhu, Ruixin; Huang, Qi; Liu, Qi; Cao, Zhiwei

    2012-03-26

    The current drug virtual screen (VS) methods mainly include two categories. i.e., ligand/target structure-based virtual screen and that, utilizing protein-ligand interaction fingerprint information based on the large number of complex structures. Since the former one focuses on the one-side information while the later one focuses on the whole complex structure, they are thus complementary and can be boosted by each other. However, a common problem faced here is how to present a comprehensive understanding and evaluation of the various virtual screen results derived from various VS methods. Furthermore, there is still an urgent need for developing an efficient approach to fully integrate various VS methods from a comprehensive multiview perspective. In this study, our virtual screen schema based on multiview similarity integration and ranking aggregation was tested comprehensively with statistical evaluations, providing several novel and useful clues on how to perform drug VS from multiple heterogeneous data sources. (1) 18 complex structures of HIV-1 protease with ligands from the PDB were curated as a test data set and the VS was performed with five different drug representations. Ritonavir ( 1HXW ) was selected as the query in VS and the weighted ranks of the query results were aggregated from multiple views through four similarity integration approaches. (2) Further, one of the ranking aggregation methods was used to integrate the similarity ranks calculated by gene ontology (GO) fingerprint and structural fingerprint on the data set from connectivity map, and two typical HDAC and HSP90 inhibitors were chosen as the queries. The results show that rank aggregation can enhance the result of similarity searching in VS when two or more descriptions are involved and provide a more reasonable similarity rank result. Our study shows that integrated VS based on multiple data fusion can achieve a remarkable better performance compared to that from individual ones and

  9. A COMPARISON OF SEMANTIC SIMILARITY MODELS IN EVALUATING CONCEPT SIMILARITY

    Directory of Open Access Journals (Sweden)

    Q. X. Xu

    2012-08-01

    Full Text Available The semantic similarities are important in concept definition, recognition, categorization, interpretation, and integration. Many semantic similarity models have been established to evaluate semantic similarities of objects or/and concepts. To find out the suitability and performance of different models in evaluating concept similarities, we make a comparison of four main types of models in this paper: the geometric model, the feature model, the network model, and the transformational model. Fundamental principles and main characteristics of these models are introduced and compared firstly. Land use and land cover concepts of NLCD92 are employed as examples in the case study. The results demonstrate that correlations between these models are very high for a possible reason that all these models are designed to simulate the similarity judgement of human mind.

  10. Towards Personalized Medicine: Leveraging Patient Similarity and Drug Similarity Analytics

    Science.gov (United States)

    Zhang, Ping; Wang, Fei; Hu, Jianying; Sorrentino, Robert

    2014-01-01

    The rapid adoption of electronic health records (EHR) provides a comprehensive source for exploratory and predictive analytic to support clinical decision-making. In this paper, we investigate how to utilize EHR to tailor treatments to individual patients based on their likelihood to respond to a therapy. We construct a heterogeneous graph which includes two domains (patients and drugs) and encodes three relationships (patient similarity, drug similarity, and patient-drug prior associations). We describe a novel approach for performing a label propagation procedure to spread the label information representing the effectiveness of different drugs for different patients over this heterogeneous graph. The proposed method has been applied on a real-world EHR dataset to help identify personalized treatments for hypercholesterolemia. The experimental results demonstrate the effectiveness of the approach and suggest that the combination of appropriate patient similarity and drug similarity analytics could lead to actionable insights for personalized medicine. Particularly, by leveraging drug similarity in combination with patient similarity, our method could perform well even on new or rarely used drugs for which there are few records of known past performance. PMID:25717413

  11. Stable non-Gaussian self-similar processes with stationary increments

    CERN Document Server

    Pipiras, Vladas

    2017-01-01

    This book provides a self-contained presentation on the structure of a large class of stable processes, known as self-similar mixed moving averages. The authors present a way to describe and classify these processes by relating them to so-called deterministic flows. The first sections in the book review random variables, stochastic processes, and integrals, moving on to rigidity and flows, and finally ending with mixed moving averages and self-similarity. In-depth appendices are also included. This book is aimed at graduate students and researchers working in probability theory and statistics.

  12. Popularity versus similarity in growing networks

    Science.gov (United States)

    Krioukov, Dmitri; Papadopoulos, Fragkiskos; Kitsak, Maksim; Serrano, Mariangeles; Boguna, Marian

    2012-02-01

    Preferential attachment is a powerful mechanism explaining the emergence of scaling in growing networks. If new connections are established preferentially to more popular nodes in a network, then the network is scale-free. Here we show that not only popularity but also similarity is a strong force shaping the network structure and dynamics. We develop a framework where new connections, instead of preferring popular nodes, optimize certain trade-offs between popularity and similarity. The framework admits a geometric interpretation, in which preferential attachment emerges from local optimization processes. As opposed to preferential attachment, the optimization framework accurately describes large-scale evolution of technological (Internet), social (web of trust), and biological (E.coli metabolic) networks, predicting the probability of new links in them with a remarkable precision. The developed framework can thus be used for predicting new links in evolving networks, and provides a different perspective on preferential attachment as an emergent phenomenon.

  13. The crystal structure of Erwinia amylovora AmyR, a member of the YbjN protein family, shows similarity to type III secretion chaperones but suggests different cellular functions.

    Science.gov (United States)

    Bartho, Joseph D; Bellini, Dom; Wuerges, Jochen; Demitri, Nicola; Toccafondi, Mirco; Schmitt, Armin O; Zhao, Youfu; Walsh, Martin A; Benini, Stefano

    2017-01-01

    AmyR is a stress and virulence associated protein from the plant pathogenic Enterobacteriaceae species Erwinia amylovora, and is a functionally conserved ortholog of YbjN from Escherichia coli. The crystal structure of E. amylovora AmyR reveals a class I type III secretion chaperone-like fold, despite the lack of sequence similarity between these two classes of protein and lacking any evidence of a secretion-associated role. The results indicate that AmyR, and YbjN proteins in general, function through protein-protein interactions without any enzymatic action. The YbjN proteins of Enterobacteriaceae show remarkably low sequence similarity with other members of the YbjN protein family in Eubacteria, yet a high level of structural conservation is observed. Across the YbjN protein family sequence conservation is limited to residues stabilising the protein core and dimerization interface, while interacting regions are only conserved between closely related species. This study presents the first structure of a YbjN protein from Enterobacteriaceae, the most highly divergent and well-studied subgroup of YbjN proteins, and an in-depth sequence and structural analysis of this important but poorly understood protein family.

  14. Towards novel organic high-Tc superconductors: Data mining using density of states similarity search

    Science.gov (United States)

    Geilhufe, R. Matthias; Borysov, Stanislav S.; Kalpakchi, Dmytro; Balatsky, Alexander V.

    2018-02-01

    Identifying novel functional materials with desired key properties is an important part of bridging the gap between fundamental research and technological advancement. In this context, high-throughput calculations combined with data-mining techniques highly accelerated this process in different areas of research during the past years. The strength of a data-driven approach for materials prediction lies in narrowing down the search space of thousands of materials to a subset of prospective candidates. Recently, the open-access organic materials database OMDB was released providing electronic structure data for thousands of previously synthesized three-dimensional organic crystals. Based on the OMDB, we report about the implementation of a novel density of states similarity search tool which is capable of retrieving materials with similar density of states to a reference material. The tool is based on the approximate nearest neighbor algorithm as implemented in the ANNOY library and can be applied via the OMDB web interface. The approach presented here is wide ranging and can be applied to various problems where the density of states is responsible for certain key properties of a material. As the first application, we report about materials exhibiting electronic structure similarities to the aromatic hydrocarbon p-terphenyl which was recently discussed as a potential organic high-temperature superconductor exhibiting a transition temperature in the order of 120 K under strong potassium doping. Although the mechanism driving the remarkable transition temperature remains under debate, we argue that the density of states, reflecting the electronic structure of a material, might serve as a crucial ingredient for the observed high Tc. To provide candidates which might exhibit comparable properties, we present 15 purely organic materials with similar features to p-terphenyl within the electronic structure, which also tend to have structural similarities with p

  15. Structure-function similarities between a plant receptor-like kinase and the human interleukin-1 receptor-associated kinase-4.

    Science.gov (United States)

    Klaus-Heisen, Dörte; Nurisso, Alessandra; Pietraszewska-Bogiel, Anna; Mbengue, Malick; Camut, Sylvie; Timmers, Ton; Pichereaux, Carole; Rossignol, Michel; Gadella, Theodorus W J; Imberty, Anne; Lefebvre, Benoit; Cullimore, Julie V

    2011-04-01

    Phylogenetic analysis has previously shown that plant receptor-like kinases (RLKs) are monophyletic with respect to the kinase domain and share an evolutionary origin with the animal interleukin-1 receptor-associated kinase/Pelle-soluble kinases. The lysin motif domain-containing receptor-like kinase-3 (LYK3) of the legume Medicago truncatula shows 33% amino acid sequence identity with human IRAK-4 over the kinase domain. Using the structure of this animal kinase as a template, homology modeling revealed that the plant RLK contains structural features particular to this group of kinases, including the tyrosine gatekeeper and the N-terminal extension α-helix B. Functional analysis revealed the importance of these conserved features for kinase activity and suggests that kinase activity is essential for the biological role of LYK3 in the establishment of the root nodule nitrogen-fixing symbiosis with rhizobia bacteria. The kinase domain of LYK3 has dual serine/threonine and tyrosine specificity, and mass spectrometry analysis identified seven serine, eight threonine, and one tyrosine residue as autophosphorylation sites in vitro. Three activation loop serine/threonine residues are required for biological activity, and molecular dynamics simulations suggest that Thr-475 is the prototypical phosphorylated residue that interacts with the conserved arginine in the catalytic loop, whereas Ser-471 and Thr-472 may be secondary sites. A threonine in the juxtamembrane region and two threonines in the C-terminal lobe of the kinase domain are important for biological but not kinase activity. We present evidence that the structure-function similarities that we have identified between LYK3 and IRAK-4 may be more widely applicable to plant RLKs in general.

  16. Different Context but Similar Cognitive Structures: Older Adults in Rural Bangladesh.

    Science.gov (United States)

    Sternäng, Ola; Lövdén, Martin; Kabir, Zarina N; Hamadani, Jena D; Wahlin, Åke

    2016-06-01

    Most research in cognitive aging is based on literate participants from high-income and Western populations. The extent to which findings generalize to low-income and illiterate populations is unknown. The main aim was to examine the structure of between-person differences in cognitive functions among elderly from rural Bangladesh. We used data from the Poverty and Health in Aging (PHA) project in Bangladesh. The participants (n = 452) were in the age range 60-92 years. Structural equation modeling was used to estimate the fit of a five-factor model (episodic recall, episodic recognition, verbal fluency, semantic knowledge, processing speed) and to examine whether the model generalized across age, sex, and literacy. This study demonstrates that an established model of cognition is valid also among older persons from rural Bangladesh. The model demonstrated strong (or scalar) invariance for age, and partial strong invariance for sex and literacy. Semantic knowledge and processing speed showed weak (or metric) sex invariance, and semantic knowledge demonstrated also sensitivity to illiteracy. In general, women performed poorer on all abilities. The structure of individual cognitive differences established in Western populations also fits a population in rural Bangladesh well. This is an important prerequisite for comparisons of cognitive functioning (e.g., declarative memory) across cultures. It is also worth noting that absolute sex differences in cognitive performance among rural elderly in Bangladesh differ from those usually found in Western samples.

  17. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

    Science.gov (United States)

    Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

    2015-05-01

    In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

  18. The nonenzymatic subunit of pseutarin C, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom, shows structural similarity to mammalian coagulation factor V.

    Science.gov (United States)

    Rao, Veena S; Swarup, Sanjay; Kini, R Manjunatha

    2003-08-15

    Pseutarin C is a group C prothrombin activator from the venom of the eastern brown snake Pseudonaja textilis. It is a multi-subunit protein complex consisting of catalytic and nonenzymatic subunits similar to coagulation factor Xa and factor Va, respectively. Here we describe the complete sequence of the nonenzymatic subunit. Based on the partial amino acid sequence of the nonenzymatic subunit, degenerate primers were designed. Using a "walking" strategy based on sequentially designed primers, we determined the complete cDNA sequence of the nonenzymatic subunit. The cDNA encodes a protein of 1461 amino acid residues, which includes a 30-residue signal peptide, a mature protein of 1430 amino acid residues, and a stop codon. cDNA blot analysis showed a single transcript of approximately 4.6 kb. The deduced amino acid sequence shows approximately 50% identity to mammalian factor V and by homology has a similar domain structure consisting of domains A1-A2-B-A3-C1-C2. Interestingly, the B domain of pseutarin C is shorter than that of mammalian factor V (FV). Although most of the proteolytic activation sites are conserved, 2 of 3 proteolytic sites cleaved by activated protein C are mutated, and thus activated protein C is not able to inactivate this procoagulant toxin. The predicted posttranslational modifications, including disulfide bonds, N-glycosylation, phosphorylation, and sulfation, in pseutarin C are significantly different compared with bovine factor V. Thus, our data demonstrate that the nonenzymatic subunit of group C prothrombin activators is structurally similar to mammalian FV.

  19. Genome-wide analysis of regions similar to promoters of histone genes

    KAUST Repository

    Chowdhary, Rajesh

    2010-05-28

    Background: The purpose of this study is to: i) develop a computational model of promoters of human histone-encoding genes (shortly histone genes), an important class of genes that participate in various critical cellular processes, ii) use the model so developed to identify regions across the human genome that have similar structure as promoters of histone genes; such regions could represent potential genomic regulatory regions, e.g. promoters, of genes that may be coregulated with histone genes, and iii/ identify in this way genes that have high likelihood of being coregulated with the histone genes.Results: We successfully developed a histone promoter model using a comprehensive collection of histone genes. Based on leave-one-out cross-validation test, the model produced good prediction accuracy (94.1% sensitivity, 92.6% specificity, and 92.8% positive predictive value). We used this model to predict across the genome a number of genes that shared similar promoter structures with the histone gene promoters. We thus hypothesize that these predicted genes could be coregulated with histone genes. This hypothesis matches well with the available gene expression, gene ontology, and pathways data. Jointly with promoters of the above-mentioned genes, we found a large number of intergenic regions with similar structure as histone promoters.Conclusions: This study represents one of the most comprehensive computational analyses conducted thus far on a genome-wide scale of promoters of human histone genes. Our analysis suggests a number of other human genes that share a high similarity of promoter structure with the histone genes and thus are highly likely to be coregulated, and consequently coexpressed, with the histone genes. We also found that there are a large number of intergenic regions across the genome with their structures similar to promoters of histone genes. These regions may be promoters of yet unidentified genes, or may represent remote control regions that

  20. Drug target identification using side-effect similarity

    DEFF Research Database (Denmark)

    Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude

    2008-01-01

    Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....

  1. Correlations between contouring similarity metrics and simulated treatment outcome for prostate radiotherapy

    Science.gov (United States)

    Roach, D.; Jameson, M. G.; Dowling, J. A.; Ebert, M. A.; Greer, P. B.; Kennedy, A. M.; Watt, S.; Holloway, L. C.

    2018-02-01

    Many similarity metrics exist for inter-observer contouring variation studies, however no correlation between metric choice and prostate cancer radiotherapy dosimetry has been explored. These correlations were investigated in this study. Two separate trials were undertaken, the first a thirty-five patient cohort with three observers, the second a five patient dataset with ten observers. Clinical and planning target volumes (CTV and PTV), rectum, and bladder were independently contoured by all observers in each trial. Structures were contoured on T2-weighted MRI and transferred onto CT following rigid registration for treatment planning in the first trial. Structures were contoured directly on CT in the second trial. STAPLE and majority voting volumes were generated as reference gold standard volumes for each structure for the two trials respectively. VMAT treatment plans (78 Gy to PTV) were simulated for observer and gold standard volumes, and dosimetry assessed using multiple radiobiological metrics. Correlations between contouring similarity metrics and dosimetry were calculated using Spearman’s rank correlation coefficient. No correlations were observed between contouring similarity metrics and dosimetry for CTV within either trial. Volume similarity correlated most strongly with radiobiological metrics for PTV in both trials, including TCPPoisson (ρ  =  0.57, 0.65), TCPLogit (ρ  =  0.39, 0.62), and EUD (ρ  =  0.43, 0.61) for each respective trial. Rectum and bladder metric correlations displayed no consistency for the two trials. PTV volume similarity was found to significantly correlate with rectum normal tissue complication probability (ρ  =  0.33, 0.48). Minimal to no correlations with dosimetry were observed for overlap or boundary contouring metrics. Future inter-observer contouring variation studies for prostate cancer should incorporate volume similarity to provide additional insights into dosimetry during analysis.

  2. Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans.

    Science.gov (United States)

    Newburg, D S

    2009-04-01

    This review discusses the role of human milk glycans in protecting infants, but the conclusion that the human milk glycans constitute an innate immune system whereby the mother protects her offspring may have general applicability in all mammals, including species of commercial importance. Infants that are not breastfed have a greater incidence of severe diarrhea and respiratory diseases than those who are breastfed. In the past, this had been attributed primarily to human milk secretory antibodies. However, the oligosaccharides are major components of human milk, and milk is also rich in other glycans, including glycoproteins, mucins, glycosaminoglycans, and glycolipids. These milk glycans, especially the oligosaccharides, are composed of thousands of components. The milk factor that promotes gut colonization by Bifidobacterium bifidum was found to be a glycan, and such prebiotic characteristics may contribute to protection against infectious agents. However, the ability of human milk glycans to protect the neonate seems primarily to be due to their inhibition of pathogen binding to their host cell target ligands. Many such examples include specific fucosylated oligosaccharides and glycans that inhibit specific pathogens. Most human milk oligosaccharides are fucosylated, and their production depends on fucosyltransferase enzymes; mutations in these fucosyltransferase genes are common and underlie the various Lewis blood types in humans. Variable expression of specific fucosylated oligosaccharides in milk, also a function of these genes (and maternal Lewis blood type), is significantly associated with the risk of infectious disease in breastfed infants. Human milk also contains major quantities and large numbers of sialylated oligosaccharides, many of which are also present in bovine colostrum. These could similarly inhibit several common viral pathogens. Moreover, human milk oligosaccharides strongly attenuate inflammatory processes in the intestinal mucosa. These

  3. Synthesis of resorcinolic lipids bearing structural similarities to cytosporone A

    International Nuclear Information System (INIS)

    Santos, Edson dos Anjos dos; Beatriz, Adilson; Lima, Denis Pires de; Marques, Maria Rita; Leite, Carla Braga

    2009-01-01

    Inspired by the structure and biological activities of resorcinolic lipids and, particularly cytosporone A- a potent inhibitor of plantule germination and growth, we have performed the synthesis of the analogs 3-heptyl-3-hydroxy-5,7-dimethoxy-2-benzofuran-1(3H)-one (1) and 3-heptyl-3-hydroxy-4,6-dimethoxy-2-benzofuran-1(3H)-one (2). The intermediates and products were submitted to allelopathic test using Lactuca sativa L. seeds. Target compound 1 showed an inhibitory effect on germination and growth of hypocotyl and radicle in millimolar range. (author)

  4. Synthesis of resorcinolic lipids bearing structural similarities to cytosporone A

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Edson dos Anjos dos; Beatriz, Adilson; Lima, Denis Pires de [Universidade Federal Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Centro de Ciencias Exatas e Tecnologia. Dept. de Quimica], e-mail: dlima@nin.ufms.br; Marques, Maria Rita; Leite, Carla Braga [Universidade Federal Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Centro de Ciencias Biologicas. Dept. de Morfofisiologia

    2009-07-01

    Inspired by the structure and biological activities of resorcinolic lipids and, particularly cytosporone A- a potent inhibitor of plantule germination and growth, we have performed the synthesis of the analogs 3-heptyl-3-hydroxy-5,7-dimethoxy-2-benzofuran-1(3H)-one (1) and 3-heptyl-3-hydroxy-4,6-dimethoxy-2-benzofuran-1(3H)-one (2). The intermediates and products were submitted to allelopathic test using Lactuca sativa L. seeds. Target compound 1 showed an inhibitory effect on germination and growth of hypocotyl and radicle in millimolar range. (author)

  5. Synthesis of resorcinolic lipids bearing structural similarities to cytosporone A

    Directory of Open Access Journals (Sweden)

    Edson dos Anjos dos Santos

    2009-01-01

    Full Text Available Inspired by the structure and biological activities of resorcinolic lipids and, particularly cytosporone A- a potent inhibitor of plantule germination and growth, we have performed the synthesis of the analogs 3-heptyl-3-hydroxy-5,7-dimethoxy-2-benzofuran-1(3H-one (1 and 3-heptyl-3-hydroxy-4,6-dimethoxy-2-benzofuran-1(3H-one (2. The intermediates and products were submitted to allelopathic test using Lactuca sativa L. seeds. Target compound 1 showed an inhibitory effect on germination and growth of hypocotyl and radicle in milimolar range.

  6. Semantic Similarity between Web Documents Using Ontology

    Science.gov (United States)

    Chahal, Poonam; Singh Tomer, Manjeet; Kumar, Suresh

    2018-06-01

    The World Wide Web is the source of information available in the structure of interlinked web pages. However, the procedure of extracting significant information with the assistance of search engine is incredibly critical. This is for the reason that web information is written mainly by using natural language, and further available to individual human. Several efforts have been made in semantic similarity computation between documents using words, concepts and concepts relationship but still the outcome available are not as per the user requirements. This paper proposes a novel technique for computation of semantic similarity between documents that not only takes concepts available in documents but also relationships that are available between the concepts. In our approach documents are being processed by making ontology of the documents using base ontology and a dictionary containing concepts records. Each such record is made up of the probable words which represents a given concept. Finally, document ontology's are compared to find their semantic similarity by taking the relationships among concepts. Relevant concepts and relations between the concepts have been explored by capturing author and user intention. The proposed semantic analysis technique provides improved results as compared to the existing techniques.

  7. Semantic Similarity between Web Documents Using Ontology

    Science.gov (United States)

    Chahal, Poonam; Singh Tomer, Manjeet; Kumar, Suresh

    2018-03-01

    The World Wide Web is the source of information available in the structure of interlinked web pages. However, the procedure of extracting significant information with the assistance of search engine is incredibly critical. This is for the reason that web information is written mainly by using natural language, and further available to individual human. Several efforts have been made in semantic similarity computation between documents using words, concepts and concepts relationship but still the outcome available are not as per the user requirements. This paper proposes a novel technique for computation of semantic similarity between documents that not only takes concepts available in documents but also relationships that are available between the concepts. In our approach documents are being processed by making ontology of the documents using base ontology and a dictionary containing concepts records. Each such record is made up of the probable words which represents a given concept. Finally, document ontology's are compared to find their semantic similarity by taking the relationships among concepts. Relevant concepts and relations between the concepts have been explored by capturing author and user intention. The proposed semantic analysis technique provides improved results as compared to the existing techniques.

  8. Similarly shaped letters evoke similar colors in grapheme-color synesthesia.

    Science.gov (United States)

    Brang, David; Rouw, Romke; Ramachandran, V S; Coulson, Seana

    2011-04-01

    Grapheme-color synesthesia is a neurological condition in which viewing numbers or letters (graphemes) results in the concurrent sensation of color. While the anatomical substrates underlying this experience are well understood, little research to date has investigated factors influencing the particular colors associated with particular graphemes or how synesthesia occurs developmentally. A recent suggestion of such an interaction has been proposed in the cascaded cross-tuning (CCT) model of synesthesia, which posits that in synesthetes connections between grapheme regions and color area V4 participate in a competitive activation process, with synesthetic colors arising during the component-stage of grapheme processing. This model more directly suggests that graphemes sharing similar component features (lines, curves, etc.) should accordingly activate more similar synesthetic colors. To test this proposal, we created and regressed synesthetic color-similarity matrices for each of 52 synesthetes against a letter-confusability matrix, an unbiased measure of visual similarity among graphemes. Results of synesthetes' grapheme-color correspondences indeed revealed that more similarly shaped graphemes corresponded with more similar synesthetic colors, with stronger effects observed in individuals with more intense synesthetic experiences (projector synesthetes). These results support the CCT model of synesthesia, implicate early perceptual mechanisms as driving factors in the elicitation of synesthetic hues, and further highlight the relationship between conceptual and perceptual factors in this phenomenon. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. A shortest-path graph kernel for estimating gene product semantic similarity

    Directory of Open Access Journals (Sweden)

    Alvarez Marco A

    2011-07-01

    Full Text Available Abstract Background Existing methods for calculating semantic similarity between gene products using the Gene Ontology (GO often rely on external resources, which are not part of the ontology. Consequently, changes in these external resources like biased term distribution caused by shifting of hot research topics, will affect the calculation of semantic similarity. One way to avoid this problem is to use semantic methods that are "intrinsic" to the ontology, i.e. independent of external knowledge. Results We present a shortest-path graph kernel (spgk method that relies exclusively on the GO and its structure. In spgk, a gene product is represented by an induced subgraph of the GO, which consists of all the GO terms annotating it. Then a shortest-path graph kernel is used to compute the similarity between two graphs. In a comprehensive evaluation using a benchmark dataset, spgk compares favorably with other methods that depend on external resources. Compared with simUI, a method that is also intrinsic to GO, spgk achieves slightly better results on the benchmark dataset. Statistical tests show that the improvement is significant when the resolution and EC similarity correlation coefficient are used to measure the performance, but is insignificant when the Pfam similarity correlation coefficient is used. Conclusions Spgk uses a graph kernel method in polynomial time to exploit the structure of the GO to calculate semantic similarity between gene products. It provides an alternative to both methods that use external resources and "intrinsic" methods with comparable performance.

  10. Investigating Correlation between Protein Sequence Similarity and Semantic Similarity Using Gene Ontology Annotations.

    Science.gov (United States)

    Ikram, Najmul; Qadir, Muhammad Abdul; Afzal, Muhammad Tanvir

    2018-01-01

    Sequence similarity is a commonly used measure to compare proteins. With the increasing use of ontologies, semantic (function) similarity is getting importance. The correlation between these measures has been applied in the evaluation of new semantic similarity methods, and in protein function prediction. In this research, we investigate the relationship between the two similarity methods. The results suggest absence of a strong correlation between sequence and semantic similarities. There is a large number of proteins with low sequence similarity and high semantic similarity. We observe that Pearson's correlation coefficient is not sufficient to explain the nature of this relationship. Interestingly, the term semantic similarity values above 0 and below 1 do not seem to play a role in improving the correlation. That is, the correlation coefficient depends only on the number of common GO terms in proteins under comparison, and the semantic similarity measurement method does not influence it. Semantic similarity and sequence similarity have a distinct behavior. These findings are of significant effect for future works on protein comparison, and will help understand the semantic similarity between proteins in a better way.

  11. Self-similar photonic crystal cavity with ultrasmall mode volume for single-photon nonlinearities

    DEFF Research Database (Denmark)

    Choi, Hyeongrak; Heuck, Mikkel; Englund, Dirk

    2017-01-01

    We propose a photonic crystal cavity design with self-similar structure to achieve ultrasmall mode volume. We describe the concept with a silicon-air nanobeam cavity at λ ∼ 1550nm, reaching a mode volume of ∼ 7.01 × 10∼5λ3.......We propose a photonic crystal cavity design with self-similar structure to achieve ultrasmall mode volume. We describe the concept with a silicon-air nanobeam cavity at λ ∼ 1550nm, reaching a mode volume of ∼ 7.01 × 10∼5λ3....

  12. Applications of Location Similarity Measures and Conceptual Spaces to Event Coreference and Classification

    Science.gov (United States)

    McConky, Katie Theresa

    2013-01-01

    This work covers topics in event coreference and event classification from spoken conversation. Event coreference is the process of identifying descriptions of the same event across sentences, documents, or structured databases. Existing event coreference work focuses on sentence similarity models or feature based similarity models requiring slot…

  13. A Quantitative Comparison of the Similarity between Genes and Geography in Worldwide Human Populations

    Science.gov (United States)

    Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A.

    2012-01-01

    Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure. PMID:22927824

  14. A quantitative comparison of the similarity between genes and geography in worldwide human populations.

    Science.gov (United States)

    Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A

    2012-08-01

    Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure.

  15. Lung structure and function similarities between primary ciliary dyskinesia and mild cystic fibrosis: a pilot study.

    Science.gov (United States)

    Maglione, Marco; Montella, Silvia; Mollica, Carmine; Carnovale, Vincenzo; Iacotucci, Paola; De Gregorio, Fabiola; Tosco, Antonella; Cervasio, Mariarosaria; Raia, Valeria; Santamaria, Francesca

    2017-04-12

    Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are increasingly compared. There are no chest magnetic resonance imaging (MRI) comparative studies of PCD and CF. We assessed clinical, functional, microbiological and MRI findings in PCD and mild CF patients in order to evaluate different expression of lung disease. Twenty PCD (15.1 years) and 20 CF subjects with mild respiratory impairment (16 years, 70% with pancreatic insufficiency) underwent MRI, spirometry, and sputum cultures when clinically stable. MRI was scored using the modified Helbich system. PCD was diagnosed later than CF (9.9 versus 0.6 years, p = 0.03), despite earlier symptoms (0.1 versus 0.6 years, p = 0.02). In the year preceding the study, patients from both groups underwent two systemic antibiotic courses (p = 0.48). MRI total scores were 11.6 ± 0.7 and 9.1 ± 1 in PCD and CF, respectively. FEV 1 and FVC Z-scores were -1.75 (range, -4.6-0.7) and -0.6 (-3.9-1.8) in PCD, and -0.9 (range, -5.4-2.3) and -0.3 (-3.4-2.5) in CF, respectively. No difference was found between lung function or structure, despite a higher MRI subscore of collapse/consolidation in PCD versus CF (1.6 ± 0.1 and 0.6 ± 0.2, p < 0.001). These findings were confirmed after data-control for diagnostic delay. Pseudomonas aeruginosa and Staphylococcus aureus were more frequent in CF than in PCD (p = 0.05 and p = 0.003, respectively). MRI is a valuable radiation-free tool for comparative PCD and CF lung disease assessment. Patients with PCD may exhibit similar MRI and lung function changes as CF subjects with mild pulmonary disease. Delay in PCD diagnosis is unlikely the only determinant of similarities.

  16. Diversity and functions of protein glycosylation in insects.

    Science.gov (United States)

    Walski, Tomasz; De Schutter, Kristof; Van Damme, Els J M; Smagghe, Guy

    2017-04-01

    The majority of proteins is modified with carbohydrate structures. This modification, called glycosylation, was shown to be crucial for protein folding, stability and subcellular location, as well as protein-protein interactions, recognition and signaling. Protein glycosylation is involved in multiple physiological processes, including embryonic development, growth, circadian rhythms, cell attachment as well as maintenance of organ structure, immunity and fertility. Although the general principles of glycosylation are similar among eukaryotic organisms, insects synthesize a distinct repertoire of glycan structures compared to plants and vertebrates. Consequently, a number of unique insect glycans mediate functions specific to this class of invertebrates. For instance, the core α1,3-fucosylation of N-glycans is absent in vertebrates, while in insects this modification is crucial for the development of wings and the nervous system. At present, most of the data on insect glycobiology comes from research in Drosophila. Yet, progressively more information on the glycan structures and the importance of glycosylation in other insects like beetles, caterpillars, aphids and bees is becoming available. This review gives a summary of the current knowledge and recent progress related to glycan diversity and function(s) of protein glycosylation in insects. We focus on N- and O-glycosylation, their synthesis, physiological role(s), as well as the molecular and biochemical basis of these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. New Similarity Functions

    DEFF Research Database (Denmark)

    Yazdani, Hossein; Ortiz-Arroyo, Daniel; Kwasnicka, Halina

    2016-01-01

    spaces, in addition to their similarity in the vector space. Prioritized Weighted Feature Distance (PWFD) works similarly as WFD, but provides the ability to give priorities to desirable features. The accuracy of the proposed functions are compared with other similarity functions on several data sets....... Our results show that the proposed functions work better than other methods proposed in the literature....

  18. EVALUATION OF SEMANTIC SIMILARITY FOR SENTENCES IN NATURAL LANGUAGE BY MATHEMATICAL STATISTICS METHODS

    Directory of Open Access Journals (Sweden)

    A. E. Pismak

    2016-03-01

    Full Text Available Subject of Research. The paper is focused on Wiktionary articles structural organization in the aspect of its usage as the base for semantic network. Wiktionary community references, article templates and articles markup features are analyzed. The problem of numerical estimation for semantic similarity of structural elements in Wiktionary articles is considered. Analysis of existing software for semantic similarity estimation of such elements is carried out; algorithms of their functioning are studied; their advantages and disadvantages are shown. Methods. Mathematical statistics methods were used to analyze Wiktionary articles markup features. The method of semantic similarity computing based on statistics data for compared structural elements was proposed.Main Results. We have concluded that there is no possibility for direct use of Wiktionary articles as the source for semantic network. We have proposed to find hidden similarity between article elements, and for that purpose we have developed the algorithm for calculation of confidence coefficients proving that each pair of sentences is semantically near. The research of quantitative and qualitative characteristics for the developed algorithm has shown its major performance advantage over the other existing solutions in the presence of insignificantly higher error rate. Practical Relevance. The resulting algorithm may be useful in developing tools for automatic Wiktionary articles parsing. The developed method could be used in computing of semantic similarity for short text fragments in natural language in case of algorithm performance requirements are higher than its accuracy specifications.

  19. Tokunaga self-similarity arises naturally from time invariance

    Science.gov (United States)

    Kovchegov, Yevgeniy; Zaliapin, Ilya

    2018-04-01

    The Tokunaga condition is an algebraic rule that provides a detailed description of the branching structure in a self-similar tree. Despite a solid empirical validation and practical convenience, the Tokunaga condition lacks a theoretical justification. Such a justification is suggested in this work. We define a geometric branching process G (s ) that generates self-similar rooted trees. The main result establishes the equivalence between the invariance of G (s ) with respect to a time shift and a one-parametric version of the Tokunaga condition. In the parameter region where the process satisfies the Tokunaga condition (and hence is time invariant), G (s ) enjoys many of the symmetries observed in a critical binary Galton-Watson branching process and reproduces the latter for a particular parameter value.

  20. Math Anxiety Questionnaire: Similar Latent Structure in Brazilian and German School Children

    Directory of Open Access Journals (Sweden)

    Guilherme Wood

    2012-01-01

    Full Text Available Math anxiety is a relatively frequent phenomenon often related to low mathematics achievement and dyscalculia. In the present study, the German and the Brazilian versions of the Mathematics Anxiety Questionnaire (MAQ were examined. The two-dimensional structure originally reported for the German MAQ, that includes both affective and cognitive components of math anxiety was reproduced in the Brazilian version. Moreover, mathematics anxiety also was found to increase with age in both populations and was particularly associated with basic numeric competencies and more complex arithmetics. The present results suggest that mathematics anxiety as measured by the MAQ presents the same internal structure in culturally very different populations.

  1. On Prolonging Network Lifetime through Load-Similar Node Deployment in Wireless Sensor Networks

    Science.gov (United States)

    Li, Qiao-Qin; Gong, Haigang; Liu, Ming; Yang, Mei; Zheng, Jun

    2011-01-01

    This paper is focused on the study of the energy hole problem in the Progressive Multi-hop Rotational Clustered (PMRC)-structure, a highly scalable wireless sensor network (WSN) architecture. Based on an analysis on the traffic load distribution in PMRC-based WSNs, we propose a novel load-similar node distribution strategy combined with the Minimum Overlapping Layers (MOL) scheme to address the energy hole problem in PMRC-based WSNs. In this strategy, sensor nodes are deployed in the network area according to the load distribution. That is, more nodes shall be deployed in the range where the average load is higher, and then the loads among different areas in the sensor network tend to be balanced. Simulation results demonstrate that the load-similar node distribution strategy prolongs network lifetime and reduces the average packet latency in comparison with existing nonuniform node distribution and uniform node distribution strategies. Note that, besides the PMRC structure, the analysis model and the proposed load-similar node distribution strategy are also applicable to other multi-hop WSN structures. PMID:22163809

  2. Substrate specificity and transfucosylation activity of GH29 α-l-fucosidases for enzymatic production of human milk oligosaccharides

    DEFF Research Database (Denmark)

    Zeuner, Birgitte; Muschiol, Jan; Holck, Jesper

    2018-01-01

    Abstract Human milk oligosaccharides (HMOs) constitute a unique family of bioactive lactose-based molecules present in human breast milk. HMOs are of major importance for infant health and development but also virtually absent from bovine milk used for infant formula. Among the HMOs...... to be able to catalyse transfucosylation. The α-l-1,3/4-fucosidase CpAfc2 from Clostridium perfringens efficiently catalysed the formation of the more complex human milk oligosaccharide structure lacto-N-fucopentaose II (LNFP II) using 3-fucosyllactose as fucosyl donor and lacto-N-tetraose as acceptor...

  3. Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J. (AbbVie)

    2017-02-21

    The rapid spread of the recentZika virus(ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 ofZika virus(ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space groupP21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

  4. [Similarity system theory to evaluate similarity of chromatographic fingerprints of traditional Chinese medicine].

    Science.gov (United States)

    Liu, Yongsuo; Meng, Qinghua; Jiang, Shumin; Hu, Yuzhu

    2005-03-01

    The similarity evaluation of the fingerprints is one of the most important problems in the quality control of the traditional Chinese medicine (TCM). Similarity measures used to evaluate the similarity of the common peaks in the chromatogram of TCM have been discussed. Comparative studies were carried out among correlation coefficient, cosine of the angle and an improved extent similarity method using simulated data and experimental data. Correlation coefficient and cosine of the angle are not sensitive to the differences of the data set. They are still not sensitive to the differences of the data even after normalization. According to the similarity system theory, an improved extent similarity method was proposed. The improved extent similarity is more sensitive to the differences of the data sets than correlation coefficient and cosine of the angle. And the character of the data sets needs not to be changed compared with log-transformation. The improved extent similarity can be used to evaluate the similarity of the chromatographic fingerprints of TCM.

  5. Assessing semantic similarity of texts - Methods and algorithms

    Science.gov (United States)

    Rozeva, Anna; Zerkova, Silvia

    2017-12-01

    Assessing the semantic similarity of texts is an important part of different text-related applications like educational systems, information retrieval, text summarization, etc. This task is performed by sophisticated analysis, which implements text-mining techniques. Text mining involves several pre-processing steps, which provide for obtaining structured representative model of the documents in a corpus by means of extracting and selecting the features, characterizing their content. Generally the model is vector-based and enables further analysis with knowledge discovery approaches. Algorithms and measures are used for assessing texts at syntactical and semantic level. An important text-mining method and similarity measure is latent semantic analysis (LSA). It provides for reducing the dimensionality of the document vector space and better capturing the text semantics. The mathematical background of LSA for deriving the meaning of the words in a given text by exploring their co-occurrence is examined. The algorithm for obtaining the vector representation of words and their corresponding latent concepts in a reduced multidimensional space as well as similarity calculation are presented.

  6. Generalized Ornstein-Uhlenbeck processes and associated self-similar processes

    CERN Document Server

    Lim, S C

    2003-01-01

    We consider three types of generalized Ornstein-Uhlenbeck processes: the stationary process obtained from the Lamperti transformation of fractional Brownian motion, the process with stretched exponential covariance and the process obtained from the solution of the fractional Langevin equation. These stationary Gaussian processes have many common properties, such as the fact that their local covariances share a similar structure and they exhibit identical spectral densities at large frequency limit. In addition, the generalized Ornstein-Uhlenbeck processes can be shown to be local stationary representations of fractional Brownian motion. Two new self-similar Gaussian processes, in addition to fractional Brownian motion, are obtained by applying the (inverse) Lamperti transformation to the generalized Ornstein-Uhlenbeck processes. We study some of the properties of these self-similar processes such as the long-range dependence. We give a simulation of their sample paths based on numerical Karhunan-Loeve expansi...

  7. Generalized Ornstein-Uhlenbeck processes and associated self-similar processes

    International Nuclear Information System (INIS)

    Lim, S C; Muniandy, S V

    2003-01-01

    We consider three types of generalized Ornstein-Uhlenbeck processes: the stationary process obtained from the Lamperti transformation of fractional Brownian motion, the process with stretched exponential covariance and the process obtained from the solution of the fractional Langevin equation. These stationary Gaussian processes have many common properties, such as the fact that their local covariances share a similar structure and they exhibit identical spectral densities at large frequency limit. In addition, the generalized Ornstein-Uhlenbeck processes can be shown to be local stationary representations of fractional Brownian motion. Two new self-similar Gaussian processes, in addition to fractional Brownian motion, are obtained by applying the (inverse) Lamperti transformation to the generalized Ornstein-Uhlenbeck processes. We study some of the properties of these self-similar processes such as the long-range dependence. We give a simulation of their sample paths based on numerical Karhunan-Loeve expansion

  8. Compression-based classification of biological sequences and structures via the Universal Similarity Metric: experimental assessment.

    Science.gov (United States)

    Ferragina, Paolo; Giancarlo, Raffaele; Greco, Valentina; Manzini, Giovanni; Valiente, Gabriel

    2007-07-13

    Similarity of sequences is a key mathematical notion for Classification and Phylogenetic studies in Biology. It is currently primarily handled using alignments. However, the alignment methods seem inadequate for post-genomic studies since they do not scale well with data set size and they seem to be confined only to genomic and proteomic sequences. Therefore, alignment-free similarity measures are actively pursued. Among those, USM (Universal Similarity Metric) has gained prominence. It is based on the deep theory of Kolmogorov Complexity and universality is its most novel striking feature. Since it can only be approximated via data compression, USM is a methodology rather than a formula quantifying the similarity of two strings. Three approximations of USM are available, namely UCD (Universal Compression Dissimilarity), NCD (Normalized Compression Dissimilarity) and CD (Compression Dissimilarity). Their applicability and robustness is tested on various data sets yielding a first massive quantitative estimate that the USM methodology and its approximations are of value. Despite the rich theory developed around USM, its experimental assessment has limitations: only a few data compressors have been tested in conjunction with USM and mostly at a qualitative level, no comparison among UCD, NCD and CD is available and no comparison of USM with existing methods, both based on alignments and not, seems to be available. We experimentally test the USM methodology by using 25 compressors, all three of its known approximations and six data sets of relevance to Molecular Biology. This offers the first systematic and quantitative experimental assessment of this methodology, that naturally complements the many theoretical and the preliminary experimental results available. Moreover, we compare the USM methodology both with methods based on alignments and not. We may group our experiments into two sets. The first one, performed via ROC (Receiver Operating Curve) analysis, aims at

  9. Compression-based classification of biological sequences and structures via the Universal Similarity Metric: experimental assessment

    Directory of Open Access Journals (Sweden)

    Manzini Giovanni

    2007-07-01

    Full Text Available Abstract Background Similarity of sequences is a key mathematical notion for Classification and Phylogenetic studies in Biology. It is currently primarily handled using alignments. However, the alignment methods seem inadequate for post-genomic studies since they do not scale well with data set size and they seem to be confined only to genomic and proteomic sequences. Therefore, alignment-free similarity measures are actively pursued. Among those, USM (Universal Similarity Metric has gained prominence. It is based on the deep theory of Kolmogorov Complexity and universality is its most novel striking feature. Since it can only be approximated via data compression, USM is a methodology rather than a formula quantifying the similarity of two strings. Three approximations of USM are available, namely UCD (Universal Compression Dissimilarity, NCD (Normalized Compression Dissimilarity and CD (Compression Dissimilarity. Their applicability and robustness is tested on various data sets yielding a first massive quantitative estimate that the USM methodology and its approximations are of value. Despite the rich theory developed around USM, its experimental assessment has limitations: only a few data compressors have been tested in conjunction with USM and mostly at a qualitative level, no comparison among UCD, NCD and CD is available and no comparison of USM with existing methods, both based on alignments and not, seems to be available. Results We experimentally test the USM methodology by using 25 compressors, all three of its known approximations and six data sets of relevance to Molecular Biology. This offers the first systematic and quantitative experimental assessment of this methodology, that naturally complements the many theoretical and the preliminary experimental results available. Moreover, we compare the USM methodology both with methods based on alignments and not. We may group our experiments into two sets. The first one, performed via ROC

  10. Similarity relations in visual search predict rapid visual categorization

    Science.gov (United States)

    Mohan, Krithika; Arun, S. P.

    2012-01-01

    How do we perform rapid visual categorization?It is widely thought that categorization involves evaluating the similarity of an object to other category items, but the underlying features and similarity relations remain unknown. Here, we hypothesized that categorization performance is based on perceived similarity relations between items within and outside the category. To this end, we measured the categorization performance of human subjects on three diverse visual categories (animals, vehicles, and tools) and across three hierarchical levels (superordinate, basic, and subordinate levels among animals). For the same subjects, we measured their perceived pair-wise similarities between objects using a visual search task. Regardless of category and hierarchical level, we found that the time taken to categorize an object could be predicted using its similarity to members within and outside its category. We were able to account for several classic categorization phenomena, such as (a) the longer times required to reject category membership; (b) the longer times to categorize atypical objects; and (c) differences in performance across tasks and across hierarchical levels. These categorization times were also accounted for by a model that extracts coarse structure from an image. The striking agreement observed between categorization and visual search suggests that these two disparate tasks depend on a shared coarse object representation. PMID:23092947

  11. Retinoid-binding proteins: similar protein architectures bind similar ligands via completely different ways.

    Directory of Open Access Journals (Sweden)

    Yu-Ru Zhang

    Full Text Available BACKGROUND: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP and epididymal retinoic acid binding protein (ERABP carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs and cellular retinoic acid-binding proteins (CRABPs carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. CONCLUSIONS/SIGNIFICANCE: Our results reveal the differences in the binding modes between the different retinoid-binding proteins.

  12. A grammar-based semantic similarity algorithm for natural language sentences.

    Science.gov (United States)

    Lee, Ming Che; Chang, Jia Wei; Hsieh, Tung Cheng

    2014-01-01

    This paper presents a grammar and semantic corpus based similarity algorithm for natural language sentences. Natural language, in opposition to "artificial language", such as computer programming languages, is the language used by the general public for daily communication. Traditional information retrieval approaches, such as vector models, LSA, HAL, or even the ontology-based approaches that extend to include concept similarity comparison instead of cooccurrence terms/words, may not always determine the perfect matching while there is no obvious relation or concept overlap between two natural language sentences. This paper proposes a sentence similarity algorithm that takes advantage of corpus-based ontology and grammatical rules to overcome the addressed problems. Experiments on two famous benchmarks demonstrate that the proposed algorithm has a significant performance improvement in sentences/short-texts with arbitrary syntax and structure.

  13. Development of a NIR-based blend uniformity method for a drug product containing multiple structurally similar actives by using the quality by design principles.

    Science.gov (United States)

    Lin, Yiqing; Li, Weiyong; Xu, Jin; Boulas, Pierre

    2015-07-05

    The aim of this study is to develop an at-line near infrared (NIR) method for the rapid and simultaneous determination of four structurally similar active pharmaceutical ingredients (APIs) in powder blends intended for the manufacturing of tablets. Two of the four APIs in the formula are present in relatively small amounts, one at 0.95% and the other at 0.57%. Such small amounts in addition to the similarity in structures add significant complexity to the blend uniformity analysis. The NIR method is developed using spectra from six laboratory-created calibration samples augmented by a small set of spectra from a large-scale blending sample. Applying the quality by design (QbD) principles, the calibration design included concentration variations of the four APIs and a main excipient, microcrystalline cellulose. A bench-top FT-NIR instrument was used to acquire the spectra. The obtained NIR spectra were analyzed by applying principal component analysis (PCA) before calibration model development. Score patterns from the PCA were analyzed to reveal relationship between latent variables and concentration variations of the APIs. In calibration model development, both PLS-1 and PLS-2 models were created and evaluated for their effectiveness in predicting API concentrations in the blending samples. The final NIR method shows satisfactory specificity and accuracy. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Similarity principles for equipment qualification by experience

    International Nuclear Information System (INIS)

    Kana, D.D.; Pomerening, D.J.

    1988-07-01

    A methodology is developed for seismic qualification of nuclear plant equipment by applying similarity principles to existing experience data. Experience data are available from previous qualifications by analysis or testing, or from actual earthquake events. Similarity principles are defined in terms of excitation, equipment physical characteristics, and equipment response. Physical similarity is further defined in terms of a critical transfer function for response at a location on a primary structure, whose response can be assumed directly related to ultimate fragility of the item under elevated levels of excitation. Procedures are developed for combining experience data into composite specifications for qualification of equipment that can be shown to be physically similar to the reference equipment. Other procedures are developed for extending qualifications beyond the original specifications under certain conditions. Some examples for application of the procedures and verification of them are given for certain cases that can be approximated by a two degree of freedom simple primary/secondary system. Other examples are based on use of actual test data available from previous qualifications. Relationships of the developments with other previously-published methods are discussed. The developments are intended to elaborate on the rather broad revised guidelines developed by the IEEE 344 Standards Committee for equipment qualification in new nuclear plants. However, the results also contribute to filling a gap that exists between the IEEE 344 methodology and that previously developed by the Seismic Qualification Utilities Group. The relationship of the results to safety margin methodology is also discussed. (author)

  15. LC-MS/MS analysis of permethylated free oligosaccharides and N-glycans derived from human, bovine, and goat milk samples.

    Science.gov (United States)

    Dong, Xue; Zhou, Shiyue; Mechref, Yehia

    2016-06-01

    Oligosaccharides in milk not only provide nutrition to the infants but also have significant immune biofunctions such as inhibition of pathogen binding to the host cell. The main component in milk oligosaccharides is free oligosaccharides. Since the proteins in milk are highly glycosylated, N-glycans in milk also play an import role. In this study, we investigated the permethylated free oligosaccharides and N-glycans extracted from bovine, goat, and human milks using LC-MS/MS. Quantitation profiles of free oligosaccharides and N-glycans were reported. The number of free oligosaccharides observed in bovine, goat, and human milk samples (without isomeric consideration) were 11, 8, and 11, respectively. Human milk had more complex free oligosaccharides structures than the other two milk samples. Totally 58, 21, and 43 N-glycan structures (without isomeric consideration) were associated with whey proteins extracted from bovine, goat, and human milk samples, respectively. Bovine milk free oligosaccharides and N-glycans from whey proteins were highly sialylated and to a lesser extend fucosylated. Goat and human milk free oligosaccharides and N-glycans from whey proteins were both highly fucosylated. Also, the isomeric glycans in milk samples were determined by porous graphitic carbon LC at elevated temperatures. For example, separation of human milk free oligosaccharide Gal-GlcNAc-(Fuc)-Gal-Glc and Gal-GlcNAc-Gal-Glc-Fuc isomers was achieved using porous graphitic carbon column. Permethylation of the glycan structures facilitated the interpretation of MS/MS. For example, internal cleavage and glycosidic bond cleavage are readily distinguished in the tandem mass spectra of permethylated glycans. This feature resulted in the identification of several isomers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Self-similar pattern formation and continuous mechanics of self-similar systems

    Directory of Open Access Journals (Sweden)

    A. V. Dyskin

    2007-01-01

    Full Text Available In many cases, the critical state of systems that reached the threshold is characterised by self-similar pattern formation. We produce an example of pattern formation of this kind – formation of self-similar distribution of interacting fractures. Their formation starts with the crack growth due to the action of stress fluctuations. It is shown that even when the fluctuations have zero average the cracks generated by them could grow far beyond the scale of stress fluctuations. Further development of the fracture system is controlled by crack interaction leading to the emergence of self-similar crack distributions. As a result, the medium with fractures becomes discontinuous at any scale. We develop a continuum fractal mechanics to model its physical behaviour. We introduce a continuous sequence of continua of increasing scales covering this range of scales. The continuum of each scale is specified by the representative averaging volume elements of the corresponding size. These elements determine the resolution of the continuum. Each continuum hides the cracks of scales smaller than the volume element size while larger fractures are modelled explicitly. Using the developed formalism we investigate the stability of self-similar crack distributions with respect to crack growth and show that while the self-similar distribution of isotropically oriented cracks is stable, the distribution of parallel cracks is not. For the isotropically oriented cracks scaling of permeability is determined. For permeable materials (rocks with self-similar crack distributions permeability scales as cube of crack radius. This property could be used for detecting this specific mechanism of formation of self-similar crack distributions.

  17. Crystal structures of the F and pSLT plasmid TraJ N-terminal regions reveal similar homodimeric PAS folds with functional interchangeability

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jun; Wu, Ruiying; Adkins, Joshua N.; Joachimiak, Andrzej; Glover, Mark

    2014-09-16

    In the F-family of conjugative plasmids, TraJ is an essential transcriptional activator of the tra operon that encodes most of the proteins required for conjugation. Here we report for the first time the X-ray crystal structures of the TraJ N-terminal regions from the prototypic F plasmid (TraJF11-130) and from the Salmonella virulence plasmid pSLT (TraJpSLT 1-128). Both proteins form similar homodimeric Per-ARNT-Sim (PAS) fold structures. Mutational analysis reveals that the observed dimeric interface is critical for TraJF transcriptional activation, indicating that dimerization of TraJ is required for its in vivo function. An artificial ligand (oxidized dithiothreitol) occupies a cavity in the TraJF dimer interface, while a smaller cavity in corresponding region of the TraJpSLT structure lacks a ligand. Gas chromatography/mass spectrometry-electron ionization analysis of dithiothreitol-free TraJF suggests indole may be the natural TraJ ligand; however, disruption of the indole biosynthetic pathway does not affect TraJF function. Heterologous PAS domains from pSLT and R100 TraJ can functionally replace the TraJF PAS domain, suggesting that TraJ allelic specificity is mediated by the region C-terminal to the PAS domain.

  18. Method of synthesis of abstract images with high self-similarity

    Science.gov (United States)

    Matveev, Nikolay V.; Shcheglov, Sergey A.; Romanova, Galina E.; Koneva, Ð.¢atiana A.

    2017-06-01

    Abstract images with high self-similarity could be used for drug-free stress therapy. This based on the fact that a complex visual environment has a high affective appraisal. To create such an image we can use the setup based on the three laser sources of small power and different colors (Red, Green, Blue), the image is the pattern resulting from the reflecting and refracting by the complicated form object placed into the laser ray paths. The images were obtained experimentally which showed the good therapy effect. However, to find and to choose the object which gives needed image structure is very difficult and requires many trials. The goal of the work is to develop a method and a procedure of finding the object form which if placed into the ray paths can provide the necessary structure of the image In fact the task means obtaining the necessary irradiance distribution on the given surface. Traditionally such problems are solved using the non-imaging optics methods. In the given case this task is very complicated because of the complicated structure of the illuminance distribution and its high non-linearity. Alternative way is to use the projected image of a mask with a given structure. We consider both ways and discuss how they can help to speed up the synthesis procedure for the given abstract image of the high self-similarity for the setups of drug-free therapy.

  19. MEASURING THE PERFORMANCE OF SIMILARITY PROPAGATION IN AN SEMANTIC SEARCH ENGINE

    Directory of Open Access Journals (Sweden)

    S. K. Jayanthi

    2013-10-01

    Full Text Available In the current scenario, web page result personalization is playing a vital role. Nearly 80 % of the users expect the best results in the first page itself without having any persistence to browse longer in URL mode. This research work focuses on two main themes: Semantic web search through online and Domain based search through offline. The first part is to find an effective method which allows grouping similar results together using BookShelf Data Structure and organizing the various clusters. The second one is focused on the academic domain based search through offline. This paper focuses on finding documents which are similar and how Vector space can be used to solve it. So more weightage is given for the principles and working methodology of similarity propagation. Cosine similarity measure is used for finding the relevancy among the documents.

  20. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

    International Nuclear Information System (INIS)

    He, Yuan; Roth, Christian; Turkenburg, Johan P.; Davies, Gideon J.

    2013-01-01

    The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily. The mammalian O-GlcNAc hydrolysing enzyme O-GlcNAcase (OGA) is a multi-domain protein with glycoside hydrolase activity in the N-terminus and with a C-terminal domain that has low sequence similarity to known acetyltransferases, prompting speculation, albeit controversial, that the C-terminal domain may function as a histone acetyltransferase (HAT). There are currently scarce data available regarding the structure and function of this C-terminal region. Here, a bacterial homologue of the human OGA C-terminal domain, an acetyltransferase protein (accession No. ZP-05014886) from Streptomyces sviceus (SsAT), was cloned and its crystal structure was solved to high resolution. The structure reveals a conserved protein core that has considerable structural homology to the acetyl-CoA (AcCoA) binding site of GCN5-related acetyltransferases (GNATs). Calorimetric data further confirm that SsAT is indeed able to bind AcCoA in solution with micromolar affinity. Detailed structural analysis provided insight into the binding of AcCoA. An acceptor-binding cavity was identified, indicating that the physiological substrate of SsAT may be a small molecule. Consistent with recently published work, the SsAT structure further questions a HAT function for the human OGA domain

  1. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

    Energy Technology Data Exchange (ETDEWEB)

    He, Yuan [Northwest University, Xi’an 710069 (China); The University of York, York YO10 5DD (United Kingdom); Roth, Christian; Turkenburg, Johan P.; Davies, Gideon J., E-mail: gideon.davies@york.ac.uk [The University of York, York YO10 5DD (United Kingdom); Northwest University, Xi’an 710069 (China)

    2014-01-01

    The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily. The mammalian O-GlcNAc hydrolysing enzyme O-GlcNAcase (OGA) is a multi-domain protein with glycoside hydrolase activity in the N-terminus and with a C-terminal domain that has low sequence similarity to known acetyltransferases, prompting speculation, albeit controversial, that the C-terminal domain may function as a histone acetyltransferase (HAT). There are currently scarce data available regarding the structure and function of this C-terminal region. Here, a bacterial homologue of the human OGA C-terminal domain, an acetyltransferase protein (accession No. ZP-05014886) from Streptomyces sviceus (SsAT), was cloned and its crystal structure was solved to high resolution. The structure reveals a conserved protein core that has considerable structural homology to the acetyl-CoA (AcCoA) binding site of GCN5-related acetyltransferases (GNATs). Calorimetric data further confirm that SsAT is indeed able to bind AcCoA in solution with micromolar affinity. Detailed structural analysis provided insight into the binding of AcCoA. An acceptor-binding cavity was identified, indicating that the physiological substrate of SsAT may be a small molecule. Consistent with recently published work, the SsAT structure further questions a HAT function for the human OGA domain.

  2. Identification of glycan structure alterations on cell membrane proteins in desoxyepothilone B resistant leukemia cells.

    Science.gov (United States)

    Nakano, Miyako; Saldanha, Rohit; Göbel, Anja; Kavallaris, Maria; Packer, Nicolle H

    2011-11-01

    Resistance to tubulin-binding agents used in cancer is often multifactorial and can include changes in drug accumulation and modified expression of tubulin isotypes. Glycans on cell membrane proteins play important roles in many cellular processes such as recognition and apoptosis, and this study investigated whether changes to the glycan structures on cell membrane proteins occur when cells become resistant to drugs. Specifically, we investigated the alteration of glycan structures on the cell membrane proteins of human T-cell acute lymphoblastic leukemia (CEM) cells that were selected for resistance to desoxyepothilone B (CEM/dEpoB). The glycan profile of the cell membrane glycoproteins was obtained by sequential release of N- and O-glycans from cell membrane fraction dotted onto polyvinylidene difluoride membrane with PNGase F and β-elimination respectively. The released glycan alditols were analyzed by liquid chromatography (graphitized carbon)-electrospray ionization tandem MS. The major N-glycan on CEM cell was the core fucosylated α2-6 monosialo-biantennary structure. Resistant CEM/dEpoB cells had a significant decrease of α2-6 linked sialic acid on N-glycans. The lower α2-6 sialylation was caused by a decrease in activity of β-galactoside α2-6 sialyltransferase (ST6Gal), and decreased expression of the mRNA. It is clear that the membrane glycosylation of leukemia cells changes during acquired resistance to dEpoB drugs and that this change occurs globally on all cell membrane glycoproteins. This is the first identification of a specific glycan modification on the surface of drug resistant cells and the mechanism of this downstream effect on microtubule targeting drugs may offer a route to new interventions to overcome drug resistance.

  3. Direct Patlak Reconstruction From Dynamic PET Data Using the Kernel Method With MRI Information Based on Structural Similarity.

    Science.gov (United States)

    Gong, Kuang; Cheng-Liao, Jinxiu; Wang, Guobao; Chen, Kevin T; Catana, Ciprian; Qi, Jinyi

    2018-04-01

    Positron emission tomography (PET) is a functional imaging modality widely used in oncology, cardiology, and neuroscience. It is highly sensitive, but suffers from relatively poor spatial resolution, as compared with anatomical imaging modalities, such as magnetic resonance imaging (MRI). With the recent development of combined PET/MR systems, we can improve the PET image quality by incorporating MR information into image reconstruction. Previously, kernel learning has been successfully embedded into static and dynamic PET image reconstruction using either PET temporal or MRI information. Here, we combine both PET temporal and MRI information adaptively to improve the quality of direct Patlak reconstruction. We examined different approaches to combine the PET and MRI information in kernel learning to address the issue of potential mismatches between MRI and PET signals. Computer simulations and hybrid real-patient data acquired on a simultaneous PET/MR scanner were used to evaluate the proposed methods. Results show that the method that combines PET temporal information and MRI spatial information adaptively based on the structure similarity index has the best performance in terms of noise reduction and resolution improvement.

  4. A similarity based agglomerative clustering algorithm in networks

    Science.gov (United States)

    Liu, Zhiyuan; Wang, Xiujuan; Ma, Yinghong

    2018-04-01

    The detection of clusters is benefit for understanding the organizations and functions of networks. Clusters, or communities, are usually groups of nodes densely interconnected but sparsely linked with any other clusters. To identify communities, an efficient and effective community agglomerative algorithm based on node similarity is proposed. The proposed method initially calculates similarities between each pair of nodes, and form pre-partitions according to the principle that each node is in the same community as its most similar neighbor. After that, check each partition whether it satisfies community criterion. For the pre-partitions who do not satisfy, incorporate them with others that having the biggest attraction until there are no changes. To measure the attraction ability of a partition, we propose an attraction index that based on the linked node's importance in networks. Therefore, our proposed method can better exploit the nodes' properties and network's structure. To test the performance of our algorithm, both synthetic and empirical networks ranging in different scales are tested. Simulation results show that the proposed algorithm can obtain superior clustering results compared with six other widely used community detection algorithms.

  5. A Grammar-Based Semantic Similarity Algorithm for Natural Language Sentences

    Science.gov (United States)

    Chang, Jia Wei; Hsieh, Tung Cheng

    2014-01-01

    This paper presents a grammar and semantic corpus based similarity algorithm for natural language sentences. Natural language, in opposition to “artificial language”, such as computer programming languages, is the language used by the general public for daily communication. Traditional information retrieval approaches, such as vector models, LSA, HAL, or even the ontology-based approaches that extend to include concept similarity comparison instead of cooccurrence terms/words, may not always determine the perfect matching while there is no obvious relation or concept overlap between two natural language sentences. This paper proposes a sentence similarity algorithm that takes advantage of corpus-based ontology and grammatical rules to overcome the addressed problems. Experiments on two famous benchmarks demonstrate that the proposed algorithm has a significant performance improvement in sentences/short-texts with arbitrary syntax and structure. PMID:24982952

  6. A Grammar-Based Semantic Similarity Algorithm for Natural Language Sentences

    Directory of Open Access Journals (Sweden)

    Ming Che Lee

    2014-01-01

    Full Text Available This paper presents a grammar and semantic corpus based similarity algorithm for natural language sentences. Natural language, in opposition to “artificial language”, such as computer programming languages, is the language used by the general public for daily communication. Traditional information retrieval approaches, such as vector models, LSA, HAL, or even the ontology-based approaches that extend to include concept similarity comparison instead of cooccurrence terms/words, may not always determine the perfect matching while there is no obvious relation or concept overlap between two natural language sentences. This paper proposes a sentence similarity algorithm that takes advantage of corpus-based ontology and grammatical rules to overcome the addressed problems. Experiments on two famous benchmarks demonstrate that the proposed algorithm has a significant performance improvement in sentences/short-texts with arbitrary syntax and structure.

  7. Correlation between protein sequence similarity and x-ray diffraction quality in the protein data bank.

    Science.gov (United States)

    Lu, Hui-Meng; Yin, Da-Chuan; Ye, Ya-Jing; Luo, Hui-Min; Geng, Li-Qiang; Li, Hai-Sheng; Guo, Wei-Hong; Shang, Peng

    2009-01-01

    As the most widely utilized technique to determine the 3-dimensional structure of protein molecules, X-ray crystallography can provide structure of the highest resolution among the developed techniques. The resolution obtained via X-ray crystallography is known to be influenced by many factors, such as the crystal quality, diffraction techniques, and X-ray sources, etc. In this paper, the authors found that the protein sequence could also be one of the factors. We extracted information of the resolution and the sequence of proteins from the Protein Data Bank (PDB), classified the proteins into different clusters according to the sequence similarity, and statistically analyzed the relationship between the sequence similarity and the best resolution obtained. The results showed that there was a pronounced correlation between the sequence similarity and the obtained resolution. These results indicate that protein structure itself is one variable that may affect resolution when X-ray crystallography is used.

  8. Phoneme Similarity and Confusability

    Science.gov (United States)

    Bailey, T.M.; Hahn, U.

    2005-01-01

    Similarity between component speech sounds influences language processing in numerous ways. Explanation and detailed prediction of linguistic performance consequently requires an understanding of these basic similarities. The research reported in this paper contrasts two broad classes of approach to the issue of phoneme similarity-theoretically…

  9. Self-similar factor approximants

    International Nuclear Information System (INIS)

    Gluzman, S.; Yukalov, V.I.; Sornette, D.

    2003-01-01

    The problem of reconstructing functions from their asymptotic expansions in powers of a small variable is addressed by deriving an improved type of approximants. The derivation is based on the self-similar approximation theory, which presents the passage from one approximant to another as the motion realized by a dynamical system with the property of group self-similarity. The derived approximants, because of their form, are called self-similar factor approximants. These complement the obtained earlier self-similar exponential approximants and self-similar root approximants. The specific feature of self-similar factor approximants is that their control functions, providing convergence of the computational algorithm, are completely defined from the accuracy-through-order conditions. These approximants contain the Pade approximants as a particular case, and in some limit they can be reduced to the self-similar exponential approximants previously introduced by two of us. It is proved that the self-similar factor approximants are able to reproduce exactly a wide class of functions, which include a variety of nonalgebraic functions. For other functions, not pertaining to this exactly reproducible class, the factor approximants provide very accurate approximations, whose accuracy surpasses significantly that of the most accurate Pade approximants. This is illustrated by a number of examples showing the generality and accuracy of the factor approximants even when conventional techniques meet serious difficulties

  10. Characterization of changes in IgG associated oligosaccharide profiles in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis using fluorophore linked carbohydrate electrophoresis.

    Science.gov (United States)

    Martin, K; Talukder, R; Hay, F C; Axford, J S

    2001-07-01

    To investigate fluorophore linked carbohydrate electrophoresis (FCE) as a method of analyzing serum immunoglobulin G (IgG) oligosaccharides in healthy individuals and those with rheumatic disease and compare with lectin binding assays of carbohydrate composition. IgG was isolated from patients with rheumatoid arthritis (RA) (n = 21), ankylosing spondylitis (AS) (n = 20), psoriatic arthritis (PsA) (n = 20), and healthy adults (n = 36). IgG oligosaccharides were released enzymatically, fluorescently labelled using 8 aminonaphthalene-136 trisulfonic acid; and identification of the oligosaccharide bands was by stepwise enzymatic degradation. Comparison of FCE was made with lectin binding analysis in which the lectins Ricinus communis (RCA1) and Bandeiraea simplicifolia (BSII) were used to detect galactose (Gal) and N-acetylglucosamine (GlcNAc), respectively. Each disease could be differentiated from healthy adults on the basis of Band 1 asialodigalacto core fucosylated oligosaccharide (gf2) intensity (p = 0.001), but not from each other. Reduced levels of different sugars were associated with specific diseases: reduced gf2 with RA (p < 0.001), PsA (p < 0.001) and AS (p < 0.02), reduced Band 5 disialo-digalacto core fucosylated (a2f) oligosaccharide with AS (p < 0.001), reduced Band 6 disialo-digalacto (a2) oligosaccharide with AS (p < 0.001) and PsA (p = 0.021). All diseases were associated with a significant increase in Band 4 asialo-agalacto core fucosylated oligosaccharide (g0f) (p < 0.001). In RA, FCE band intensities correlated with sugar quantity when identified using lectin binding analysis (p < 0.003). In contrast, there was no correlation between the same bands in healthy individuals. FCE is an accurate method of analyzing IgG associated oligosaccharides and reveals unique band patterns or sugar prints associated with healthy adults and patients with RA, PsA, and AS, and comparison with lectin binding analysis suggests undetected RA glycoprotein structural

  11. Associative Interference in Pavlovian Conditioning: A Function of Similarity Between the Interfering and Target Associative Structures

    OpenAIRE

    Amundson, Jeffrey C.; Miller, Ralph R.

    2008-01-01

    Three lever-press suppression studies were conducted with water-deprived rats to investigate the role of similarity in proactive interference within first-order Pavlovian conditioning. Experiments 1a and 1b assessed the influence of stimulus complexity in proactive interference. Both experiments found greater interference when the interfering cue and target cue were composed of the same number of elements. Experiment 2 assessed the influence of context similarity in proactive interference and...

  12. Retrospective group fusion similarity search based on eROCE evaluation metric.

    Science.gov (United States)

    Avram, Sorin I; Crisan, Luminita; Bora, Alina; Pacureanu, Liliana M; Avram, Stefana; Kurunczi, Ludovic

    2013-03-01

    In this study, a simple evaluation metric, denoted as eROCE was proposed to measure the early enrichment of predictive methods. We demonstrated the superior robustness of eROCE compared to other known metrics throughout several active to inactive ratios ranging from 1:10 to 1:1000. Group fusion similarity search was investigated by varying 16 similarity coefficients, five molecular representations (binary and non-binary) and two group fusion rules using two reference structure set sizes. We used a dataset of 3478 actives and 43,938 inactive molecules and the enrichment was analyzed by means of eROCE. This retrospective study provides optimal similarity search parameters in the case of ALDH1A1 inhibitors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Nuclear markers reveal that inter-lake cichlids' similar morphologies do not reflect similar genealogy.

    Science.gov (United States)

    Kassam, Daud; Seki, Shingo; Horic, Michio; Yamaoka, Kosaku

    2006-08-01

    The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.

  14. Determination of subjective similarity for pairs of masses and pairs of clustered microcalcifications on mammograms: Comparison of similarity ranking scores and absolute similarity ratings

    International Nuclear Information System (INIS)

    Muramatsu, Chisako; Li Qiang; Schmidt, Robert A.; Shiraishi, Junji; Suzuki, Kenji; Newstead, Gillian M.; Doi, Kunio

    2007-01-01

    The presentation of images that are similar to that of an unknown lesion seen on a mammogram may be helpful for radiologists to correctly diagnose that lesion. For similar images to be useful, they must be quite similar from the radiologists' point of view. We have been trying to quantify the radiologists' impression of similarity for pairs of lesions and to establish a ''gold standard'' for development and evaluation of a computerized scheme for selecting such similar images. However, it is considered difficult to reliably and accurately determine similarity ratings, because they are subjective. In this study, we compared the subjective similarities obtained by two different methods, an absolute rating method and a 2-alternative forced-choice (2AFC) method, to demonstrate that reliable similarity ratings can be determined by the responses of a group of radiologists. The absolute similarity ratings were previously obtained for pairs of masses and pairs of microcalcifications from five and nine radiologists, respectively. In this study, similarity ranking scores for eight pairs of masses and eight pairs of microcalcifications were determined by use of the 2AFC method. In the first session, the eight pairs of masses and eight pairs of microcalcifications were grouped and compared separately for determining the similarity ranking scores. In the second session, another similarity ranking score was determined by use of mixed pairs, i.e., by comparison of the similarity of a mass pair with that of a calcification pair. Four pairs of masses and four pairs of microcalcifications were grouped together to create two sets of eight pairs. The average absolute similarity ratings and the average similarity ranking scores showed very good correlations in the first study (Pearson's correlation coefficients: 0.94 and 0.98 for masses and microcalcifications, respectively). Moreover, in the second study, the correlations between the absolute ratings and the ranking scores were also

  15. Similarity Measure of Graphs

    Directory of Open Access Journals (Sweden)

    Amine Labriji

    2017-07-01

    Full Text Available The topic of identifying the similarity of graphs was considered as highly recommended research field in the Web semantic, artificial intelligence, the shape recognition and information research. One of the fundamental problems of graph databases is finding similar graphs to a graph query. Existing approaches dealing with this problem are usually based on the nodes and arcs of the two graphs, regardless of parental semantic links. For instance, a common connection is not identified as being part of the similarity of two graphs in cases like two graphs without common concepts, the measure of similarity based on the union of two graphs, or the one based on the notion of maximum common sub-graph (SCM, or the distance of edition of graphs. This leads to an inadequate situation in the context of information research. To overcome this problem, we suggest a new measure of similarity between graphs, based on the similarity measure of Wu and Palmer. We have shown that this new measure satisfies the properties of a measure of similarities and we applied this new measure on examples. The results show that our measure provides a run time with a gain of time compared to existing approaches. In addition, we compared the relevance of the similarity values obtained, it appears that this new graphs measure is advantageous and  offers a contribution to solving the problem mentioned above.

  16. Extending the Similarity-Attraction Effect : The effects of When-Similarity in mediated communication

    NARCIS (Netherlands)

    Kaptein, M.C.; Castaneda, D.; Fernandez, N.; Nass, C.

    2014-01-01

    The feeling of connectedness experienced in computer-mediated relationships can be explained by the similarity-attraction effect (SAE). Though SAE is well established in psychology, the effects of some types of similarity have not yet been explored. In 2 studies, we demonstrate similarity-attraction

  17. The semantic similarity ensemble

    Directory of Open Access Journals (Sweden)

    Andrea Ballatore

    2013-12-01

    Full Text Available Computational measures of semantic similarity between geographic terms provide valuable support across geographic information retrieval, data mining, and information integration. To date, a wide variety of approaches to geo-semantic similarity have been devised. A judgment of similarity is not intrinsically right or wrong, but obtains a certain degree of cognitive plausibility, depending on how closely it mimics human behavior. Thus selecting the most appropriate measure for a specific task is a significant challenge. To address this issue, we make an analogy between computational similarity measures and soliciting domain expert opinions, which incorporate a subjective set of beliefs, perceptions, hypotheses, and epistemic biases. Following this analogy, we define the semantic similarity ensemble (SSE as a composition of different similarity measures, acting as a panel of experts having to reach a decision on the semantic similarity of a set of geographic terms. The approach is evaluated in comparison to human judgments, and results indicate that an SSE performs better than the average of its parts. Although the best member tends to outperform the ensemble, all ensembles outperform the average performance of each ensemble's member. Hence, in contexts where the best measure is unknown, the ensemble provides a more cognitively plausible approach.

  18. Network similarity and statistical analysis of earthquake seismic data

    OpenAIRE

    Deyasi, Krishanu; Chakraborty, Abhijit; Banerjee, Anirban

    2016-01-01

    We study the structural similarity of earthquake networks constructed from seismic catalogs of different geographical regions. A hierarchical clustering of underlying undirected earthquake networks is shown using Jensen-Shannon divergence in graph spectra. The directed nature of links indicates that each earthquake network is strongly connected, which motivates us to study the directed version statistically. Our statistical analysis of each earthquake region identifies the hub regions. We cal...

  19. Stereotype content model across cultures: Towards universal similarities and some differences

    Science.gov (United States)

    Cuddy, Amy J. C.; Fiske, Susan T.; Kwan, Virginia S. Y.; Glick, Peter; Demoulin, Stéphanie; Leyens, Jacques-Philippe; Bond, Michael Harris; Croizet, Jean-Claude; Ellemers, Naomi; Sleebos, Ed; Htun, Tin Tin; Kim, Hyun-Jeong; Maio, Greg; Perry, Judi; Petkova, Kristina; Todorov, Valery; Rodríguez-Bailón, Rosa; Morales, Elena; Moya, Miguel; Palacios, Marisol; Smith, Vanessa; Perez, Rolando; Vala, Jorge; Ziegler, Rene

    2014-01-01

    The stereotype content model (SCM) proposes potentially universal principles of societal stereotypes and their relation to social structure. Here, the SCM reveals theoretically grounded, cross-cultural, cross-groups similarities and one difference across 10 non-US nations. Seven European (individualist) and three East Asian (collectivist) nations (N = 1, 028) support three hypothesized cross-cultural similarities: (a) perceived warmth and competence reliably differentiate societal group stereotypes; (b) many out-groups receive ambivalent stereotypes (high on one dimension; low on the other); and (c) high status groups stereotypically are competent, whereas competitive groups stereotypically lack warmth. Data uncover one consequential cross-cultural difference: (d) the more collectivist cultures do not locate reference groups (in-groups and societal prototype groups) in the most positive cluster (high-competence/high-warmth), unlike individualist cultures. This demonstrates out-group derogation without obvious reference-group favouritism. The SCM can serve as a pancultural tool for predicting group stereotypes from structural relations with other groups in society, and comparing across societies. PMID:19178758

  20. Similar Symmetries: The Role of Wallpaper Groups in Perceptual Texture Similarity

    Directory of Open Access Journals (Sweden)

    Fraser Halley

    2011-05-01

    Full Text Available Periodic patterns and symmetries are striking visual properties that have been used decoratively around the world throughout human history. Periodic patterns can be mathematically classified into one of 17 different Wallpaper groups, and while computational models have been developed which can extract an image's symmetry group, very little work has been done on how humans perceive these patterns. This study presents the results from a grouping experiment using stimuli from the different wallpaper groups. We find that while different images from the same wallpaper group are perceived as similar to one another, not all groups have the same degree of self-similarity. The similarity relationships between wallpaper groups appear to be dominated by rotations.

  1. A tetraantennary glycan with bisecting N-acetylglucosamine and the Sda antigen is the predominant N-glycan on bovine pregnancy-associated glycoproteins

    DEFF Research Database (Denmark)

    Klisch, Karl; Jeanrond, Evelyne; Pang, Poh-Choo

    2008-01-01

    assisted laser desorption ionisation-mass spectrometry (MALDI-MS) analysis and linkage analysis, we show that by far, the most abundant N-glycan of PAGs in midpregnancy is a tetraantennary core-fucosylated structure with a bisecting N-acetylglucosamine (GlcNAc). All four antennae consist of the Sd......(a)-antigen (NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4GlcNAc-). Immunohistochemistry with the mono- clonal antibody CT1, which recognizes the Sd(a)-antigen, shows that BNC granules contain the Sd(a)-antigen from gestation day (gd) 32 until a few days before parturition. Lectin histochemistry with Maackia amurensis...

  2. Building scientific confidence in metabolic similarity in read-across through the use of in vitro, in silico and analytical data

    Science.gov (United States)

    The underlying principle of read-across is that the biological activity of a chemical is inherent in its molecular structure. Analogues are typically identified by structural similarity then evaluated on the basis of their bioavailability, reactivity and metabolic similarity. Whi...

  3. Self-similarity of proton spin and asymmetry of jet production

    International Nuclear Information System (INIS)

    Tokarev, M.V.; Zborovsky, I.

    2014-01-01

    Self-similarity of jet production in polarized p + p collisions is studied. The concept of z-scaling is applied for description of inclusive spectra obtained with different orientations of proton spin. New data on the double longitudinal spin asymmetry, A LL , of jets produced in proton-proton collisions at √s = 200 GeV measured by the STAR Collaboration at RHIC are analyzed in the z-scaling approach. Hypotheses of self-similarity and fractality of internal spin structure are formulated. A possibility to extract information on spin-dependent fractal dimensions of proton from the asymmetry of jet production is justified. The spin-dependent fractal dimensions for the process p-bar+p-bar→jet+X are estimated.

  4. SHOP: scaffold hopping by GRID-based similarity searches

    DEFF Research Database (Denmark)

    Bergmann, Rikke; Linusson, Anna; Zamora, Ismael

    2007-01-01

    A new GRID-based method for scaffold hopping (SHOP) is presented. In a fully automatic manner, scaffolds were identified in a database based on three types of 3D-descriptors. SHOP's ability to recover scaffolds was assessed and validated by searching a database spiked with fragments of known...... scaffolds were in the 31 top-ranked scaffolds. SHOP also identified new scaffolds with substantially different chemotypes from the queries. Docking analysis indicated that the new scaffolds would have similar binding modes to those of the respective query scaffolds observed in X-ray structures...

  5. Personality traits across countries: Support for similarities rather than differences.

    Science.gov (United States)

    Kajonius, Petri; Mac Giolla, Erik

    2017-01-01

    In the current climate of migration and globalization, personality characteristics of individuals from different countries have received a growing interest. Previous research has established reliable differences in personality traits across countries. The present study extends this research by examining 30 personality traits in 22 countries, based on an online survey in English with large national samples (NTotal = 130,602). The instrument used was a comprehensive, open-source measure of the Five Factor Model (FFM) (IPIP-NEO-120). We postulated that differences in personality traits between countries would be small, labeling this a Similarities Hypothesis. We found support for this in three stages. First, similarities across countries were observed for model fits for each of the five personality trait structures. Second, within-country sex differences for the five personality traits showed similar patterns across countries. Finally, the overall the contribution to personality traits from countries was less than 2%. In other words, the relationship between a country and an individual's personality traits, however interesting, are small. We conclude that the most parsimonious explanation for the current and past findings is a cross-country personality Similarities Hypothesis.

  6. Genomic rearrangements and functional diversification of lecA and lecB lectin-coding regions impacting the efficacy of glycomimetics directed against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Amine M Boukerb

    2016-05-01

    Full Text Available LecA and LecB tetrameric lectins take part in oligosaccharide-mediated adhesion-processes of Pseudomonas aeruginosa. Glycomimetics have been designed to block these interactions. The great versatility of P. aeruginosa suggests that the range of application of these glycomimetics could be restricted to genotypes with particular lectin types. The likelihood of having genomic and genetic changes impacting LecA and LecB interactions with glycomimetics such as galactosylated and fucosylated calix[4]arene was investigated over a collection of strains from the main clades of P. aeruginosa. Lectin types were defined, and their ligand specificities were inferred. These analyses showed a loss of lecA among the PA7 clade. Genomic changes impacting lec loci were thus assessed using strains of this clade, and by making comparisons with the PAO1 genome. The lecA regions were found challenged by phage attacks and PAGI-2 (genomic island integrations. A prophage was linked to the loss of lecA. The lecB regions were found less impacted by such rearrangements but greater lecB than lecA genetic divergences were recorded. Sixteen combinations of LecA and LecB types were observed. Amino acid variations were mapped on PAO1 crystal structures. Most significant changes were observed on LecBPA7, and found close to the fucose binding site. Glycan array analyses were performed with purified LecBPA7. LecBPA7 was found less specific for fucosylated oligosaccharides than LecBPAO1, with a preference for H type 2 rather than type 1, and Lewisa rather than Lewisx. Comparison of the crystal structures of LecBPA7 and LecBPAO1 in complex with Lewisa showed these changes in specificity to have resulted from a modification of the water network between the lectin, galactose and GlcNAc residues. Incidence of these modifications on the interactions with calix[4]arene glycomimetics at the cell level was investigated. An aggregation test was used to establish the efficacy of these ligands

  7. Beyond common features: The role of roles in determining similarity1

    Science.gov (United States)

    Jones, Matt; Love, Bradley C.

    2007-01-01

    Historically, accounts of object representation and perceived similarity have focused on intrinsic features. Although more recent accounts have explored how objects, scenes, and situations containing common relational structures come to be perceived as similar, less is known about how the perceived similarity of parts or objects embedded within these relational systems is affected. The current studies test the hypothesis that objects situated in common relational systems come to be perceived as more similar. Similarity increases most for objects playing the same role within a relation (e.g., predator), but also increases for objects playing different roles within the same relation (e.g., the predator or prey role in the hunts relation) regardless of whether the objects participate in the same instance of the relation. This pattern of results can be captured by extending existing models that extract meaning from text corpora so that they are sensitive to the verb-specific thematic roles that objects fill. Alternative explanations based on analogical and inferential processes are also considered, as well as the implications of the current findings to research in language processing, personality and person perception, decision making, and category learning. PMID:17094958

  8. N-glycosylation profile of undifferentiated and adipogenically differentiated human bone marrow mesenchymal stem cells: towards a next generation of stem cell markers.

    Science.gov (United States)

    Hamouda, Houda; Ullah, Mujib; Berger, Markus; Sittinger, Michael; Tauber, Rudolf; Ringe, Jochen; Blanchard, Véronique

    2013-12-01

    Mesenchymal stem cells (MSCs) are multipotent cells that are easy to isolate and expand, develop into several tissues, including fat, migrate to diseased organs, have immunosuppressive properties and secrete regenerative factors. This makes MSCs ideal for regenerative medicine. For application and regulatory purposes, knowledge of (bio)markers characterizing MSCs and their development stages is of paramount importance. The cell surface is coated with glycans that possess lineage-specific nature, which makes glycans to be promising candidate markers. In the context of soft tissue generation, we aimed to identify glycans that could be markers for MSCs and their adipogenically differentiated progeny. MSCs were isolated from human bone marrow, adipogenically stimulated for 15 days and adipogenesis was verified by staining the lipid droplets and quantitative real time polymerase chain reaction of the marker genes peroxisome proliferator-activated receptor gamma (PPARG) and fatty acid binding protein-4 (FABP4). Using matrix-assisted laser desorption-ionization-time of flight mass spectrometry combined with exoglycosidase digestions, we report for the first time the N-glycome of MSCs during adipogenic differentiation. We were able to detect more than 100 different N-glycans, including high-mannose, hybrid, and complex N-glycans, as well as poly-N-acetyllactosamine chains. Adipogenesis was accompanied by an increased amount of biantennary fucosylated structures, decreased amount of fucosylated, afucosylated tri- and tetraantennary structures and increased sialylation. N-glycans H6N5F1 and H7N6F1 were significantly overexpressed in undifferentiated MSCs while H3N4F1 and H5N4F3 were upregulated in adipogenically differentiated MSCs. These glycan structures are promising candidate markers to detect and distinguish MSCs and their adipogenic progeny.

  9. Gender similarities and differences.

    Science.gov (United States)

    Hyde, Janet Shibley

    2014-01-01

    Whether men and women are fundamentally different or similar has been debated for more than a century. This review summarizes major theories designed to explain gender differences: evolutionary theories, cognitive social learning theory, sociocultural theory, and expectancy-value theory. The gender similarities hypothesis raises the possibility of theorizing gender similarities. Statistical methods for the analysis of gender differences and similarities are reviewed, including effect sizes, meta-analysis, taxometric analysis, and equivalence testing. Then, relying mainly on evidence from meta-analyses, gender differences are reviewed in cognitive performance (e.g., math performance), personality and social behaviors (e.g., temperament, emotions, aggression, and leadership), and psychological well-being. The evidence on gender differences in variance is summarized. The final sections explore applications of intersectionality and directions for future research.

  10. Extended local similarity analysis (eLSA) reveals unique associations between bacterial community structure and odor emission during pig carcasses decomposition.

    Science.gov (United States)

    Ki, Bo-Min; Ryu, Hee Wook; Cho, Kyung-Suk

    2018-02-22

    Soil burial and composting methods have been widely used for the disposal of pig carcasses. The relationship between bacterial community structure and odor emission was examined using extended local similarity analysis (eLSA) during the degradation of pig carcasses in soil and compost. In soil, Hyphomicrobium, Niastella, Rhodanobacter, Polaromonas, Dokdonella and Mesorhizobium were associated with the emission of sulfur-containing odors such as hydrogen sulfide, methyl mercaptan and dimethyl disulfide. Sphingomonas, Rhodanobacter, Mesorhizobium, Dokdonella, Leucobacter and Truepera were associated with the emission of nitrogen-containing odors including ammonia and trimetylamine. In compost, however, Carnobacteriaceae, Lachnospiaceae and Clostridiales were highly correlated with the emission of sulfur-containing odors, while Rumincoccaceae was associated with the emission of nitrogen-containing odors. The emission of organic acids was closely related to Massilia, Sphaerobacter and Bradyrhizobiaceae in soil, but to Actinobacteria, Sporacetigenium, Micromonosporaceae and Solirubrobacteriales in compost. This study suggests that network analysis using eLSA is a useful strategy for exploring the mechanisms of odor emission during biodegradation of pig carcasses.

  11. MAK33 antibody light chain amyloid fibrils are similar to oligomeric precursors.

    Directory of Open Access Journals (Sweden)

    Manuel Hora

    Full Text Available Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues of the CDR2 and the β-strands D, E, F and G of the native immunoglobulin fold. The assigned core region of the fibril is distinct in comparison to the core identified in a previous solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can adopt different topologies. In addition, we investigated a soluble oligomeric intermediate state, previously termed the alternatively folded state (AFS, using NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of similarity when compared to the fibril spectra, indicating a high structural similarity of the two aggregation states. Based on comparison to the native state NMR chemical shifts, we suggest that fibril formation via domain-swapping seems unlikely. Moreover, we used our results to test the quality of different amyloid prediction algorithms.

  12. Defining a similarity threshold for a functional proteinsequence pattern: The signal peptide cleavage site

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; von Heijne, Gunnar

    1996-01-01

    When preparing data sets of amino acid or nucleotide sequences it is necessary to exclude redundant or homologous sequences in order to avoid overestimating the predictive performance of an algorithm. For some time methods for doing this have been available in the area of protein structure...... prediction. We have developed a similar procedure based on pair-wise alignments for sequences with functional sites. We show how a correlation coefficient between sequence similarity and functional homology can be used to compare the efficiency of different similarity measures and choose a nonarbitrary...

  13. Extending the Similarity-Attraction Effect: The Effects of When-Similarity in Computer-Mediated Communication

    NARCIS (Netherlands)

    Kaptein, M.C.; Castaneda, D.; Fernandez, N.; Nass, C.

    2014-01-01

    The feeling of connectedness experienced in computer-mediated relationships can be explained by the similarity-attraction effect (SAE). Though SAE is well established in psychology, the effects of some types of similarity have not yet been explored. In 2 studies, we demonstrate similarity-attraction

  14. Dynamics based alignment of proteins: an alternative approach to quantify dynamic similarity

    Directory of Open Access Journals (Sweden)

    Lyngsø Rune

    2010-04-01

    Full Text Available Abstract Background The dynamic motions of many proteins are central to their function. It therefore follows that the dynamic requirements of a protein are evolutionary constrained. In order to assess and quantify this, one needs to compare the dynamic motions of different proteins. Comparing the dynamics of distinct proteins may also provide insight into how protein motions are modified by variations in sequence and, consequently, by structure. The optimal way of comparing complex molecular motions is, however, far from trivial. The majority of comparative molecular dynamics studies performed to date relied upon prior sequence or structural alignment to define which residues were equivalent in 3-dimensional space. Results Here we discuss an alternative methodology for comparative molecular dynamics that does not require any prior alignment information. We show it is possible to align proteins based solely on their dynamics and that we can use these dynamics-based alignments to quantify the dynamic similarity of proteins. Our method was tested on 10 representative members of the PDZ domain family. Conclusions As a result of creating pair-wise dynamics-based alignments of PDZ domains, we have found evolutionarily conserved patterns in their backbone dynamics. The dynamic similarity of PDZ domains is highly correlated with their structural similarity as calculated with Dali. However, significant differences in their dynamics can be detected indicating that sequence has a more refined role to play in protein dynamics than just dictating the overall fold. We suggest that the method should be generally applicable.

  15. Toward translational incremental similarity-based reasoning in breast cancer grading

    Science.gov (United States)

    Tutac, Adina E.; Racoceanu, Daniel; Leow, Wee-Keng; Müller, Henning; Putti, Thomas; Cretu, Vladimir

    2009-02-01

    One of the fundamental issues in bridging the gap between the proliferation of Content-Based Image Retrieval (CBIR) systems in the scientific literature and the deficiency of their usage in medical community is based on the characteristic of CBIR to access information by images or/and text only. Yet, the way physicians are reasoning about patients leads intuitively to a case representation. Hence, a proper solution to overcome this gap is to consider a CBIR approach inspired by Case-Based Reasoning (CBR), which naturally introduces medical knowledge structured by cases. Moreover, in a CBR system, the knowledge is incrementally added and learned. The purpose of this study is to initiate a translational solution from CBIR algorithms to clinical practice, using a CBIR/CBR hybrid approach. Therefore, we advance the idea of a translational incremental similarity-based reasoning (TISBR), using combined CBIR and CBR characteristics: incremental learning of medical knowledge, medical case-based structure of the knowledge (CBR), image usage to retrieve similar cases (CBIR), similarity concept (central for both paradigms). For this purpose, three major axes are explored: the indexing, the cases retrieval and the search refinement, applied to Breast Cancer Grading (BCG), a powerful breast cancer prognosis exam. The effectiveness of this strategy is currently evaluated over cases provided by the Pathology Department of Singapore National University Hospital, for the indexing. With its current accuracy, TISBR launches interesting perspectives for complex reasoning in future medical research, opening the way to a better knowledge traceability and a better acceptance rate of computer-aided diagnosis assistance among practitioners.

  16. Similarities and differences in borderline and organic personality disorder.

    Science.gov (United States)

    Mathiesen, Birgit B; Simonsen, Erik; Soegaard, Ulf; Kvist, Kajsa

    2014-01-01

    Previous research has shown that brain injury patients with Organic Personality Disorder (OPD) may display "borderline" traits due to prefrontal damage, and their personality structure may be unstable and close to a borderline personality organisation. They may have few general neuropsychological dysfunctions but specific executive deficits. Similar deficits have been found in patients with Borderline Personality Disorder (BPD). The objective of this study was to identify differences and similarities between the neuropsychological and personality profiles of BPD and OPD patients. Twenty BPD patients and 24 OPD patients were assessed with the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), the Karolinska Psychodynamic Profile (KAPP), and a comprehensive neuropsychological test battery. Very few neuropsychological differences were found between the two patient groups. However, the verbal fluency, verbal intelligence, verbal memory, and immediate auditory memory/attention of the BPD patients were significantly poorer than the OPD patients'. The KAPP profiles of the BPD patients showed significantly poorer functioning in three areas: frustration tolerance, the body as a factor of self-esteem, and overall personality organisation. These results support our clinical experience and expectations concerning the severity of symptoms of both patient groups. We suggest considering in depth assessments of both neuropsychological and personality-related problems for each of these patients in order to inform treatment.

  17. Nanoindentation of HMX and Idoxuridine to Determine Mechanical Similarity

    Directory of Open Access Journals (Sweden)

    Alexandra C. Burch

    2017-11-01

    Full Text Available Assessing the mechanical behavior (elastic properties, plastic properties, and fracture phenomena of molecular crystals is often complicated by the difficulty in preparing samples. Pharmaceuticals and energetic materials in particular are often used in composite structures or tablets, where the individual grains can strongly impact the solid behavior. Nanoindentation is a convenient method to experimentally assess these properties, and it is used here to demonstrate the similarity in the mechanical properties of two distinct systems: individual crystals of the explosive cyclotetramethylene tetranitramine (HMX and the pharmaceutical idoxuridine were tested in their as-precipitated state, and the effective average modulus and hardness (which can be orientation dependent were determined. Both exhibit a hardness of 1.0 GPa, with an effective reduced modulus of 25 and 23 GPa for the HMX and idoxuridine, respectively. They also exhibit similar yield point behavior. This indicates idoxuridine may be a suitable mechanical surrogate (or “mock” for HMX. While the methodology to assess elastic and plastic properties was relatively insensitive to specific crystal orientation (i.e., a uniform distribution in properties was observed for all random crystals tested, the indentation-induced fracture properties appear to be much more sensitive to tip-crystal orientation, and an unloading slope analysis is used to demonstrate the need for further refinement in relating toughness to orientation in these materials with relatively complex slip systems and crystal structures.

  18. Protein structure similarity clustering (PSSC) and natural product structure as inspiration sources for drug development and chemical genomics

    NARCIS (Netherlands)

    Dekker, Frank J; Koch, Marcus A; Waldmann, Herbert; Dekker, Frans

    Finding small molecules that modulate protein function is of primary importance in drug development and in the emerging field of chemical genomics. To facilitate the identification of such molecules, we developed a novel strategy making use of structural conservatism found in protein domain

  19. A self-similar magnetohydrodynamic model for ball lightnings

    International Nuclear Information System (INIS)

    Tsui, K. H.

    2006-01-01

    Ball lightning is modeled by magnetohydrodynamic (MHD) equations in two-dimensional spherical geometry with azimuthal symmetry. Dynamic evolutions in the radial direction are described by the self-similar evolution function y(t). The plasma pressure, mass density, and magnetic fields are solved in terms of the radial label η. This model gives spherical MHD plasmoids with axisymmetric force-free magnetic field, and spherically symmetric plasma pressure and mass density, which self-consistently determine the polytropic index γ. The spatially oscillating nature of the radial and meridional field structures indicate embedded regions of closed field lines. These regions are named secondary plasmoids, whereas the overall self-similar spherical structure is named the primary plasmoid. According to this model, the time evolution function allows the primary plasmoid expand outward in two modes. The corresponding ejection of the embedded secondary plasmoids results in ball lightning offering an answer as how they come into being. The first is an accelerated expanding mode. This mode appears to fit plasmoids ejected from thundercloud tops with acceleration to ionosphere seen in high altitude atmospheric observations of sprites and blue jets. It also appears to account for midair high-speed ball lightning overtaking airplanes, and ground level high-speed energetic ball lightning. The second is a decelerated expanding mode, and it appears to be compatible to slowly moving ball lightning seen near ground level. The inverse of this second mode corresponds to an accelerated inward collapse, which could bring ball lightning to an end sometimes with a cracking sound

  20. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    Directory of Open Access Journals (Sweden)

    Heike Wolf

    2016-09-01

    Full Text Available Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1 was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6-GlcNAc(β1-N-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS. On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.

  1. Role of ABO secretor status in mucosal innate immunity and H. pylori infection.

    Directory of Open Access Journals (Sweden)

    Sara Lindén

    2008-01-01

    Full Text Available The fucosylated ABH antigens, which constitute the molecular basis for the ABO blood group system, are also expressed in salivary secretions and gastrointestinal epithelia in individuals of positive secretor status; however, the biological function of the ABO blood group system is unknown. Gastric mucosa biopsies of 41 Rhesus monkeys originating from Southern Asia were analyzed by immunohistochemistry. A majority of these animals were found to be of blood group B and weak-secretor phenotype (i.e., expressing both Lewis a and Lewis b antigens, which are also common in South Asian human populations. A selected group of ten monkeys was inoculated with Helicobacter pylori and studied for changes in gastric mucosal glycosylation during a 10-month period. We observed a loss in mucosal fucosylation and concurrent induction and time-dependent dynamics in gastric mucosal sialylation (carbohydrate marker of inflammation, which affect H. pylori adhesion targets and thus modulate host-bacterial interactions. Of particular relevance, gastric mucosal density of H. pylori, gastritis, and sialylation were all higher in secretor individuals compared to weak-secretors, the latter being apparently "protected." These results demonstrate that the secretor status plays an intrinsic role in resistance to H. pylori infection and suggest that the fucosylated secretor ABH antigens constitute interactive members of the human and primate mucosal innate immune system.

  2. FX enzyme and GDP-L-Fuc transporter expression in colorectal cancer.

    Science.gov (United States)

    Villar-Portela, Susana; Muinelo-Romay, Laura; Cuevas, Elisa; Gil-Martín, Emilio; Fernández-Briera, Almudena

    2013-08-01

    Fucosylation is regulated by fucosyltransferases, the guanosine diphosphate-L-fucose (GDP-L-Fuc) synthetic pathway, and the GDP-L-fucose transporter (GDP-L-Fuc Tr). We have reported previously an increased level of α(1,6)fucosyltransferase activity and expression in colorectal cancer (CRC). The present study aimed to analyse the expression profiles of the FX enzyme and GDP-L-Fuc Tr in a cohort of operated CRC patients to elucidate their role in α(1,6)fucosylation in this neoplasm. We assessed the immunohistochemical expression of FX and GDP-L-Fuc Tr in a series of tumour samples and healthy tissues from CRC specimens. FX expression was observed in 58 of 91 (63.7%) tumours and 23 of 28 (82.1%) corresponding healthy samples. GDP-L-Fuc Tr expression was detected in 86 of 102 (84.3%) colorectal tumours, and 13 of 27 (48.1%) healthy tissue specimens. The expression of GDP-L-Fuc Tr was statistically higher in tumours than in healthy tissues (P GDP-L-Fuc Tr expression in tumour samples (P = 0.003). GDP-L-Fuc Tr overexpression in the tumour tissue of CRC patients suggests that GDP-L-Fuc transport to the Golgi apparatus may be an important factor associated with increased α(1,6)fucosylation in CRC. © 2013 John Wiley & Sons Ltd.

  3. Contextual Factors for Finding Similar Experts

    DEFF Research Database (Denmark)

    Hofmann, Katja; Balog, Krisztian; Bogers, Toine

    2010-01-01

    -seeking models, are rarely taken into account. In this article, we extend content-based expert-finding approaches with contextual factors that have been found to influence human expert finding. We focus on a task of science communicators in a knowledge-intensive environment, the task of finding similar experts......, given an example expert. Our approach combines expertise-seeking and retrieval research. First, we conduct a user study to identify contextual factors that may play a role in the studied task and environment. Then, we design expert retrieval models to capture these factors. We combine these with content......-based retrieval models and evaluate them in a retrieval experiment. Our main finding is that while content-based features are the most important, human participants also take contextual factors into account, such as media experience and organizational structure. We develop two principled ways of modeling...

  4. On different forms of self similarity

    International Nuclear Information System (INIS)

    Aswathy, R.K.; Mathew, Sunil

    2016-01-01

    Fractal geometry is mainly based on the idea of self-similar forms. To be self-similar, a shape must able to be divided into parts that are smaller copies, which are more or less similar to the whole. There are different forms of self similarity in nature and mathematics. In this paper, some of the topological properties of super self similar sets are discussed. It is proved that in a complete metric space with two or more elements, the set of all non super self similar sets are dense in the set of all non-empty compact sub sets. It is also proved that the product of self similar sets are super self similar in product metric spaces and that the super self similarity is preserved under isometry. A characterization of super self similar sets using contracting sub self similarity is also presented. Some relevant counterexamples are provided. The concepts of exact super and sub self similarity are introduced and a necessary and sufficient condition for a set to be exact super self similar in terms of condensation iterated function systems (Condensation IFS’s) is obtained. A method to generate exact sub self similar sets using condensation IFS’s and the denseness of exact super self similar sets are also discussed.

  5. Similarity principles for seismic qualification of equipment by experience data

    International Nuclear Information System (INIS)

    Kana, D.D.; Pomerening, D.J.

    1989-01-01

    A methodology is developed for seismic qualification of nuclear plant equipment by applying similarity principles to existing experience data. Experience data is that available from previous qualifications by analysis or testing, or from actual earthquake events. Similarity principles are defined in terms of excitation, equipment physical characteristics, and equipment response. Physical similarity is further defined in terms of a critical transfer function for response at a location on a primary structure, whose response can be assumed directly related to fragility of the item under elevated levels of excitation. Procedures are developed for combining experience data into composite specifications for qualification of equipment that can be shown to be physically similar to the reference equipment. Other procedures are developed for extending qualifications beyond the original specifications under certain conditions. Some examples for application and verification of the procedures are given for actual test data available from previous qualifications. The developments are intended to elaborate on the rather broad guidelines by the IEEE 344 Standards Committee for equipment qualification in new nuclear plants. The results also contribute to filling a gap that exists between the IEEE 344 methodology and that which was previously developed for equipment in existing plants by the Seismic Qualification Utilities Group. 10 refs., 9 figs., 1 tab

  6. Social Trust and Value Similarity: the Relationship between Social Trust and Human Values in Europe

    Directory of Open Access Journals (Sweden)

    Mai Beilmann

    2015-12-01

    Full Text Available The purpose of the current paper is to test whether value similarity may foster social trust in society and whether people have higher levels of social trust when they emphasise the same values that prevail in their country. The relationship between social trust and human values was examined in a sample of 51,308 people across 29 European countries using data from the European Social Survey round 6. Results suggest that value similarity is more important in generating individual level social trust in countries where the overall levels of social trust are higher. There is a stronger positive relationship between value similarity and social trust in Scandinavian countries, which have high social trust levels, while in countries with a low level of social trust, congruity of the personal value structure with the country level value structure tends to decrease the individuals trustfulness

  7. Judgments of brand similarity

    NARCIS (Netherlands)

    Bijmolt, THA; Wedel, M; Pieters, RGM; DeSarbo, WS

    This paper provides empirical insight into the way consumers make pairwise similarity judgments between brands, and how familiarity with the brands, serial position of the pair in a sequence, and the presentation format affect these judgments. Within the similarity judgment process both the

  8. Self-similar continued root approximants

    International Nuclear Information System (INIS)

    Gluzman, S.; Yukalov, V.I.

    2012-01-01

    A novel method of summing asymptotic series is advanced. Such series repeatedly arise when employing perturbation theory in powers of a small parameter for complicated problems of condensed matter physics, statistical physics, and various applied problems. The method is based on the self-similar approximation theory involving self-similar root approximants. The constructed self-similar continued roots extrapolate asymptotic series to finite values of the expansion parameter. The self-similar continued roots contain, as a particular case, continued fractions and Padé approximants. A theorem on the convergence of the self-similar continued roots is proved. The method is illustrated by several examples from condensed-matter physics.

  9. Designing novel Sn-Bi, Si-C and Ge-C nanostructures, using simple theoretical chemical similarities

    Directory of Open Access Journals (Sweden)

    Zdetsis Aristides

    2011-01-01

    Full Text Available Abstract A framework of simple, transparent and powerful concepts is presented which is based on isoelectronic (or isovalent principles, analogies, regularities and similarities. These analogies could be considered as conceptual extensions of the periodical table of the elements, assuming that two atoms or molecules having the same number of valence electrons would be expected to have similar or homologous properties. In addition, such similar moieties should be able, in principle, to replace each other in more complex structures and nanocomposites. This is only partly true and only occurs under certain conditions which are investigated and reviewed here. When successful, these concepts are very powerful and transparent, leading to a large variety of nanomaterials based on Si and other group 14 elements, similar to well known and well studied analogous materials based on boron and carbon. Such nanomaterias designed in silico include, among many others, Si-C, Sn-Bi, Si-C and Ge-C clusters, rings, nanowheels, nanorodes, nanocages and multidecker sandwiches, as well as silicon planar rings and fullerenes similar to the analogous sp2 bonding carbon structures. It is shown that this pedagogically simple and transparent framework can lead to an endless variety of novel and functional nanomaterials with important potential applications in nanotechnology, nanomedicine and nanobiology. Some of the so called predicted structures have been already synthesized, not necessarily with the same rational and motivation. Finally, it is anticipated that such powerful and transparent rules and analogies, in addition to their predictive power, could also lead to far-reaching interpretations and a deeper understanding of already known results and information.

  10. The similarity of twin brains; Die Aehnlichkeit von Zwillingsgehirnen

    Energy Technology Data Exchange (ETDEWEB)

    Mohr, A.; Knauth, M.; Stippich, C.; Sartor, K. [Abt. Neuroradiologie, Univ. Heidelberg (Germany); Weisbrod, M. [Sektion Experimentelle Psychopathologie, Psychiatrische Klinik Univ. Heidelberg (Germany)

    2001-06-01

    To test the assumption underlying every morphometric twin study that the brains of monozygotic twins are almost identical. Methods: High resolution MRI of the neurocranium of 26 monozygotic twin pairs were acquired and the volumes of 36 cerebral structures were measured. The same twins served as control group after rear-ranging them into non-related pairs of same sex and matching them for age, body height and body weight. Results: For most of the examined structures the correlations within the twins were significant (R = 0,97-0,59). Except for total forebrain volume the controls showed no significant similarity. Conclusions: For almost every measured cerebral structure the assumption, that significant similarities exist between healthy monozygotic twins is correct. Therefore discordant monozygotic twins represent an excellent sample when investigating cerebral correlates of neurologic and psychiatric disorders. (orig.) [German] Pruefung der Grundannahme hirnmorphologischer Zwillingsstudien, dass die Gehirne eineiiger Zwillinge signifikant aehnlich sind. Methode: Hochaufloesende MRT-Datensaetze der Gehirne von 26 gesunden eineiigen Zwillingspaaren dienten als Grundlage der volumetrischen Vermessung von insgesamt 36 zerebralen Strukturen. Als Kontrollkollektiv wurden neue, nicht verwandte, aber gleichgeschlechtliche und nach Alter, Koerpergroesse und Koerpergewicht sehr aehnliche Paare gebildet. Ergebnisse: Fuer Hemisphaerenvolumen, graue und weisse Substanz des Frontal- und Temporallappens (R = 0,97-0,59) sowie fuer zahlreiche subkortikale Strukturen (R = 0,80-0,41) zeigten sich signifikante (p < 0,05) Korrelationen zwischen den Zwillingspaaren. Ausser fuer Grosshirnvolumen fanden sich bei den Kontrollpaaren keine signifikanten Aehnlichkeiten. Schlussfolgerung: Fuer die meisten der vermessenen zerebralen Areale ist die Annahme richtig, dass die Gehirne eineliger Zwillinge deutlich aehnlicher sind als die Gehirne nicht verwandter Personen. Bei der Suche nach

  11. The potential indirect effects among plants via shared hummingbird pollinators are structured by phenotypic similarity.

    Science.gov (United States)

    Bergamo, Pedro Joaquim; Wolowski, Marina; Maruyama, Pietro Kiyoshi; Vizentin-Bugoni, Jeferson; Carvalheiro, Luísa G; Sazima, Marlies

    2017-07-01

    Plant species within communities may overlap in pollinators' use and influence visitation patterns of shared pollinators, potentially engaging in indirect interactions (e.g., facilitation or competition). While several studies have explored the mechanisms regulating insect-pollination networks, there is a lack of studies on bird-pollination systems, particularly in species-rich tropical areas. Here, we evaluated if phenotypic similarity, resource availability (floral abundance), evolutionary relatedness and flowering phenology affect the potential for indirect effects via shared pollinators in hummingbird-pollinated plant species within four communities in the Brazilian Atlantic forest. Among the evaluated factors, phenotypic similarity (corolla length and anther height) was the most important variable, while resource availability (floral abundance) had a secondary importance. On the other hand, evolutionary relatedness and flowering phenology were less important, which altogether highlights the relevance of convergent evolution and that the contribution of a plant to the diet of the pollinators of another plant is independent of the level of temporal overlap in flowering in this tropical system. Interestingly, our findings contrast with results from multiple insect-pollinated plant communities, mostly from temperate regions, in which floral abundance was the most important driver, followed by evolutionary relatedness and phenotypic similarity. We propose that these contrasting results are due to high level of specialization inherent to tropical hummingbird-pollination systems. Moreover, our results demonstrated that factors defining linkage rules of plant-hummingbird networks also determinate plant-plant potential indirect effects. Future studies are needed to test if these findings can be generalized to other highly specialized systems. Overall, our results have important implications for the understanding of ecological processes due resource sharing in

  12. Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

    Science.gov (United States)

    Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

    2014-04-04

    α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Personalized recommendation with corrected similarity

    International Nuclear Information System (INIS)

    Zhu, Xuzhen; Tian, Hui; Cai, Shimin

    2014-01-01

    Personalized recommendation has attracted a surge of interdisciplinary research. Especially, similarity-based methods in applications of real recommendation systems have achieved great success. However, the computations of similarities are overestimated or underestimated, in particular because of the defective strategy of unidirectional similarity estimation. In this paper, we solve this drawback by leveraging mutual correction of forward and backward similarity estimations, and propose a new personalized recommendation index, i.e., corrected similarity based inference (CSI). Through extensive experiments on four benchmark datasets, the results show a greater improvement of CSI in comparison with these mainstream baselines. And a detailed analysis is presented to unveil and understand the origin of such difference between CSI and mainstream indices. (paper)

  14. A similarity hypothesis for the two-point correlation tensor in a temporally evolving plane wake

    Science.gov (United States)

    Ewing, D. W.; George, W. K.; Moser, R. D.; Rogers, M. M.

    1995-01-01

    The analysis demonstrated that the governing equations for the two-point velocity correlation tensor in the temporally evolving wake admit similarity solutions, which include the similarity solutions for the single-point moment as a special case. The resulting equations for the similarity solutions include two constants, beta and Re(sub sigma), that are ratios of three characteristic time scales of processes in the flow: a viscous time scale, a time scale characteristic of the spread rate of the flow, and a characteristic time scale of the mean strain rate. The values of these ratios depend on the initial conditions of the flow and are most likely measures of the coherent structures in the initial conditions. The occurrences of these constants in the governing equations for the similarity solutions indicates that these solutions, in general, will only be the same for two flows if these two constants are equal (and hence the coherent structures in the flows are related). The comparisons between the predictions of the similarity hypothesis and the data presented here and elsewhere indicate that the similarity solutions for the two-point correlation tensors provide a good approximation of the measures of those motions that are not significantly affected by the boundary conditions caused by the finite extent of real flows. Thus, the two-point similarity hypothesis provides a useful tool for both numerical and physical experimentalist that can be used to examine how the finite extent of real flows affect the evolution of the different scales of motion in the flow.

  15. The effect of lineup member similarity on recognition accuracy in simultaneous and sequential lineups.

    Science.gov (United States)

    Flowe, Heather D; Ebbesen, Ebbe B

    2007-02-01

    Two experiments investigated whether remembering is affected by the similarity of the study face relative to the alternatives in a lineup. In simultaneous and sequential lineups, choice rates and false alarms were larger in low compared to high similarity lineups, indicating criterion placement was affected by lineup similarity structure (Experiment 1). In Experiment 2, foil choices and similarity ranking data for target present lineups were compared to responses made when the target was removed from the lineup (only the 5 foils were presented). The results indicated that although foils were selected more often in target-removed lineups in the simultaneous compared to the sequential condition, responses shifted from the target to one of the foils at equal rates across lineup procedures.

  16. A novel numerical framework for self-similarity in plasticity: Wedge indentation in single crystals

    Science.gov (United States)

    Juul, K. J.; Niordson, C. F.; Nielsen, K. L.; Kysar, J. W.

    2018-03-01

    A novel numerical framework for analyzing self-similar problems in plasticity is developed and demonstrated. Self-similar problems of this kind include processes such as stationary cracks, void growth, indentation etc. The proposed technique offers a simple and efficient method for handling this class of complex problems by avoiding issues related to traditional Lagrangian procedures. Moreover, the proposed technique allows for focusing the mesh in the region of interest. In the present paper, the technique is exploited to analyze the well-known wedge indentation problem of an elastic-viscoplastic single crystal. However, the framework may be readily adapted to any constitutive law of interest. The main focus herein is the development of the self-similar framework, while the indentation study serves primarily as verification of the technique by comparing to existing numerical and analytical studies. In this study, the three most common metal crystal structures will be investigated, namely the face-centered cubic (FCC), body-centered cubic (BCC), and hexagonal close packed (HCP) crystal structures, where the stress and slip rate fields around the moving contact point singularity are presented.

  17. Binary similarity measures for fingerprint analysis of qualitative metabolomic profiles.

    Science.gov (United States)

    Rácz, Anita; Andrić, Filip; Bajusz, Dávid; Héberger, Károly

    2018-01-01

    Contemporary metabolomic fingerprinting is based on multiple spectrometric and chromatographic signals, used either alone or combined with structural and chemical information of metabolic markers at the qualitative and semiquantitative level. However, signal shifting, convolution, and matrix effects may compromise metabolomic patterns. Recent increase in the use of qualitative metabolomic data, described by the presence (1) or absence (0) of particular metabolites, demonstrates great potential in the field of metabolomic profiling and fingerprint analysis. The aim of this study is a comprehensive evaluation of binary similarity measures for the elucidation of patterns among samples of different botanical origin and various metabolomic profiles. Nine qualitative metabolomic data sets covering a wide range of natural products and metabolomic profiles were applied to assess 44 binary similarity measures for the fingerprinting of plant extracts and natural products. The measures were analyzed by the novel sum of ranking differences method (SRD), searching for the most promising candidates. Baroni-Urbani-Buser (BUB) and Hawkins-Dotson (HD) similarity coefficients were selected as the best measures by SRD and analysis of variance (ANOVA), while Dice (Di1), Yule, Russel-Rao, and Consonni-Todeschini 3 ranked the worst. ANOVA revealed that concordantly and intermediately symmetric similarity coefficients are better candidates for metabolomic fingerprinting than the asymmetric and correlation based ones. The fingerprint analysis based on the BUB and HD coefficients and qualitative metabolomic data performed equally well as the quantitative metabolomic profile analysis. Fingerprint analysis based on the qualitative metabolomic profiles and binary similarity measures proved to be a reliable way in finding the same/similar patterns in metabolomic data as that extracted from quantitative data.

  18. A Molecular–Structure Hypothesis

    Directory of Open Access Journals (Sweden)

    Jan C. A. Boeyens

    2010-11-01

    Full Text Available The self-similar symmetry that occurs between atomic nuclei, biological growth structures, the solar system, globular clusters and spiral galaxies suggests that a similar pattern should characterize atomic and molecular structures. This possibility is explored in terms of the current molecular structure-hypothesis and its extension into four-dimensional space-time. It is concluded that a quantum molecule only has structure in four dimensions and that classical (Newtonian structure, which occurs in three dimensions, cannot be simulated by quantum-chemical computation.

  19. On the Development and Use of Large Chemical Similarity Networks, Informatics Best Practices and Novel Chemical Descriptors Towards Materials Quantitative Structure Property Relationships

    Science.gov (United States)

    Krein, Michael

    After decades of development and use in a variety of application areas, Quantitative Structure Property Relationships (QSPRs) and related descriptor-based statistical learning methods have achieved a level of infamy due to their misuse. The field is rife with past examples of overtrained models, overoptimistic performance assessment, and outright cheating in the form of explicitly removing data to fit models. These actions do not serve the community well, nor are they beneficial to future predictions based on established models. In practice, in order to select combinations of descriptors and machine learning methods that might work best, one must consider the nature and size of the training and test datasets, be aware of existing hypotheses about the data, and resist the temptation to bias structure representation and modeling to explicitly fit the hypotheses. The definition and application of these best practices is important for obtaining actionable modeling outcomes, and for setting user expectations of modeling accuracy when predicting the endpoint values of unknowns. A wide variety of statistical learning approaches, descriptor types, and model validation strategies are explored herein, with the goals of helping end users understand the factors involved in creating and using QSPR models effectively, and to better understand relationships within the data, especially by looking at the problem space from multiple perspectives. Molecular relationships are commonly envisioned in a continuous high-dimensional space of numerical descriptors, referred to as chemistry space. Descriptor and similarity metric choice influence the partitioning of this space into regions corresponding to local structural similarity. These regions, known as domains of applicability, are most likely to be successfully modeled by a QSPR. In Chapter 2, the network topology and scaling relationships of several chemistry spaces are thoroughly investigated. Chemistry spaces studied include the

  20. 20180312 - Building scientific confidence in metabolic similarity in read-across through the use of in vitro, in silico and analytical data (SOT)

    Science.gov (United States)

    The underlying principle of read-across is that the biological activity of a chemical is inherent in its molecular structure. Analogues are typically identified by structural similarity then evaluated on the basis of their bioavailability, reactivity and metabolic similarity. Whi...

  1. Herbaspirillum seropedicae signal transduction protein PII is structurally similar to the enteric GlnK.

    Science.gov (United States)

    Machado Benelli, Elaine; Buck, Martin; Polikarpov, Igor; Maltempi de Souza, Emanuel; Cruz, Leonardo M; Pedrosa, Fábio O

    2002-07-01

    PII-like proteins are signal transduction proteins found in bacteria, archaea and eukaryotes. They mediate a variety of cellular responses. A second PII-like protein, called GlnK, has been found in several organisms. In the diazotroph Herbaspirillum seropedicae, PII protein is involved in sensing nitrogen levels and controlling nitrogen fixation genes. In this work, the crystal structure of the unliganded H. seropedicae PII was solved by X-ray diffraction. H. seropedicae PII has a Gly residue, Gly108 preceding Pro109 and the main-chain forms a beta turn. The glycine at position 108 allows a bend in the C-terminal main-chain, thereby modifying the surface of the cleft between monomers and potentially changing function. The structure suggests that the C-terminal region of PII proteins may be involved in specificity of function, and nonenteric diazotrophs are found to have the C-terminal consensus XGXDAX(107-112). We are also proposing binding sites for ATP and 2-oxoglutarate based on the structural alignment of PII with PII-ATP/GlnK-ATP, 5-carboxymethyl-2-hydroxymuconate isomerase and 4-oxalocrotonate tautomerase bound to the inhibitor 2-oxo-3-pentynoate.

  2. Query-dependent banding (QDB for faster RNA similarity searches.

    Directory of Open Access Journals (Sweden)

    Eric P Nawrocki

    2007-03-01

    Full Text Available When searching sequence databases for RNAs, it is desirable to score both primary sequence and RNA secondary structure similarity. Covariance models (CMs are probabilistic models well-suited for RNA similarity search applications. However, the computational complexity of CM dynamic programming alignment algorithms has limited their practical application. Here we describe an acceleration method called query-dependent banding (QDB, which uses the probabilistic query CM to precalculate regions of the dynamic programming lattice that have negligible probability, independently of the target database. We have implemented QDB in the freely available Infernal software package. QDB reduces the average case time complexity of CM alignment from LN(2.4 to LN(1.3 for a query RNA of N residues and a target database of L residues, resulting in a 4-fold speedup for typical RNA queries. Combined with other improvements to Infernal, including informative mixture Dirichlet priors on model parameters, benchmarks also show increased sensitivity and specificity resulting from improved parameterization.

  3. Hartley and Itokawa: small comet and asteroid with similar morphologies and structures

    Science.gov (United States)

    Kochemasov, G. G.

    2011-10-01

    at the convex bulge, from the antipodean side (Fig. 5). The smaller rocky asteroid Itokawa (0.5 km long, Fig. 2) is surprisingly similar in shape and structure to the icy core of Hart ley. It is also bent and rich in cross-cutting lineations o 4 direct ions marked by small holes-craters. But here they are ext inct and lack of gas -dust jets. One sees a transition from a volat ile rich comet core to an ext inct mostly rocky mass - asteroid. In both cases (comet core and as teroid) in the middle develops a smooth "wais t". The bulged convex and antipodal concave segments -hemispheres in rotating bodies require somewhat different densities of composing them masses to equilibrate angular momentum of two halves (compare with the Ea rth's hemis pheres : the eas tern continental "granitic" and wes tern Pacific "bas altic"). The near-IR images of two asteroids (Fig.6-7) confirm this. The concave and convex s ides are co mpos itionally d ifferent. In the Eros ' cas e the concave s ide is rich er in pyroxene, thus denser.

  4. Similar or different?: the importance of similarities and differences for support between siblings

    NARCIS (Netherlands)

    Voorpostel, M.; van der Lippe, T.; Dykstra, P.A.; Flap, H.

    2007-01-01

    Using a large-scale Dutch national sample (N = 7,126), the authors examine the importance of similarities and differences in the sibling dyad for the provision of support. Similarities are assumed to enhance attraction and empathy; differences are assumed to be related to different possibilities for

  5. Similar or Different? The Importance of Similarities and Differences for Support Between Siblings

    NARCIS (Netherlands)

    Voorpostel, Marieke; Lippe, Tanja van der; Dykstra, Pearl A.; Flap, Henk

    2007-01-01

    Using a large-scale Dutch national sample (N = 7,126), the authors examine the importance of similarities and differences in the sibling dyad for the provision of support. Similarities are assumed to enhance attraction and empathy; differences are assumed to be related to different possibilities for

  6. Centrifugal fans: Similarity, scaling laws, and fan performance

    Science.gov (United States)

    Sardar, Asad Mohammad

    Centrifugal fans are rotodynamic machines used for moving air continuously against moderate pressures through ventilation and air conditioning systems. There are five major topics presented in this thesis: (1) analysis of the fan scaling laws and consequences of dynamic similarity on modelling; (2) detailed flow visualization studies (in water) covering the flow path starting at the fan blade exit to the evaporator core of an actual HVAC fan scroll-diffuser module; (3) mean velocity and turbulence intensity measurements (flow field studies) at the inlet and outlet of large scale blower; (4) fan installation effects on overall fan performance and evaluation of fan testing methods; (5) two point coherence and spectral measurements conducted on an actual HVAC fan module for flow structure identification of possible aeroacoustic noise sources. A major objective of the study was to identity flow structures within the HVAC module that are responsible for noise and in particular "rumble noise" generation. Possible mechanisms for the generation of flow induced noise in the automotive HVAC fan module are also investigated. It is demonstrated that different modes of HVAC operation represent very different internal flow characteristics. This has implications on both fan HVAC airflow performance and noise characteristics. It is demonstrated from principles of complete dynamic similarity that fan scaling laws require that Reynolds, number matching is a necessary condition for developing scale model fans or fan test facilities. The physical basis for the fan scaling laws derived was established from both pure dimensional analysis and also from the fundamental equations of fluid motion. Fan performance was measured in a three times scale model (large scale blower) in air of an actual forward curved automotive HVAC blower. Different fan testing methods (based on AMCA fan test codes) were compared on the basis of static pressure measurements. Also, the flow through an actual HVAC

  7. Self-similar two-particle separation model

    DEFF Research Database (Denmark)

    Lüthi, Beat; Berg, Jacob; Ott, Søren

    2007-01-01

    .g.; in the inertial range as epsilon−1/3r2/3. Particle separation is modeled as a Gaussian process without invoking information of Eulerian acceleration statistics or of precise shapes of Eulerian velocity distribution functions. The time scale is a function of S2(r) and thus of the Lagrangian evolving separation......We present a new stochastic model for relative two-particle separation in turbulence. Inspired by material line stretching, we suggest that a similar process also occurs beyond the viscous range, with time scaling according to the longitudinal second-order structure function S2(r), e....... The model predictions agree with numerical and experimental results for various initial particle separations. We present model results for fixed time and fixed scale statistics. We find that for the Richardson-Obukhov law, i.e., =gepsilont3, to hold and to also be observed in experiments, high Reynolds...

  8. An Efficient Similarity Digests Database Lookup - A Logarithmic Divide & Conquer Approach

    Directory of Open Access Journals (Sweden)

    Frank Breitinger

    2014-09-01

    Full Text Available Investigating seized devices within digital forensics represents a challenging task due to the increasing amount of data. Common procedures utilize automated file identification, which reduces the amount of data an investigator has to examine manually. In the past years the research field of approximate matching arises to detect similar data. However, if n denotes the number of similarity digests in a database, then the lookup for a single similarity digest is of complexity of O(n. This paper presents a concept to extend existing approximate matching algorithms, which reduces the lookup complexity from O(n to O(log(n. Our proposed approach is based on the well-known divide and conquer paradigm and builds a Bloom filter-based tree data structure in order to enable an efficient lookup of similarity digests. Further, it is demonstrated that the presented technique is highly scalable operating a trade-off between storage requirements and computational efficiency. We perform a theoretical assessment based on recently published results and reasonable magnitudes of input data, and show that the complexity reduction achieved by the proposed technique yields a 220-fold acceleration of look-up costs.

  9. Being similar while judging right and wrong: The effects of personal and situational similarity on moral judgements.

    Science.gov (United States)

    Pascal, Emilia

    2017-07-20

    This study investigated the effects of similarity with the transgressor and the victim on the perceived immorality of the transgression. Participants read two stories describing a person that cheated on their partner and a police officer that mistreated somebody. In the first story we manipulated participants' personal similarity to the transgressor and in the second their personal similarity to the victim. In each story, participants' past situational similarity to the target character was assessed according to their previous experiences of being in the same position. Results show that both personal and past situational similarity to the transgressor determine less severe moral judgements, while personal and past situational similarity with the victim have the opposite effect. We also tested several potential mediators of these effects, derived from competing theoretical accounts of the influence of similarity on perceived responsibility. Empathy emerged as mediating most of the effects of similarity on moral judgements, except those induced by past situational similarity with the victim. The foreseen probability of being in a similar situation mediated only the effects of similarity to the transgressor, and not those of similarity to the victim. Overall, results highlight the complex mechanisms of the influences of similarity on moral judgements. © 2017 International Union of Psychological Science.

  10. Self-similar cosmological models

    Energy Technology Data Exchange (ETDEWEB)

    Chao, W Z [Cambridge Univ. (UK). Dept. of Applied Mathematics and Theoretical Physics

    1981-07-01

    The kinematics and dynamics of self-similar cosmological models are discussed. The degrees of freedom of the solutions of Einstein's equations for different types of models are listed. The relation between kinematic quantities and the classifications of the self-similarity group is examined. All dust local rotational symmetry models have been found.

  11. Self-similarity in the inertial region of wall turbulence.

    Science.gov (United States)

    Klewicki, J; Philip, J; Marusic, I; Chauhan, K; Morrill-Winter, C

    2014-12-01

    The inverse of the von Kármán constant κ is the leading coefficient in the equation describing the logarithmic mean velocity profile in wall bounded turbulent flows. Klewicki [J. Fluid Mech. 718, 596 (2013)] connects the asymptotic value of κ with an emerging condition of dynamic self-similarity on an interior inertial domain that contains a geometrically self-similar hierarchy of scaling layers. A number of properties associated with the asymptotic value of κ are revealed. This is accomplished using a framework that retains connection to invariance properties admitted by the mean statement of dynamics. The development leads toward, but terminates short of, analytically determining a value for κ. It is shown that if adjacent layers on the hierarchy (or their adjacent positions) adhere to the same self-similarity that is analytically shown to exist between any given layer and its position, then κ≡Φ(-2)=0.381966..., where Φ=(1+√5)/2 is the golden ratio. A number of measures, derived specifically from an analysis of the mean momentum equation, are subsequently used to empirically explore the veracity and implications of κ=Φ(-2). Consistent with the differential transformations underlying an invariant form admitted by the governing mean equation, it is demonstrated that the value of κ arises from two geometric features associated with the inertial turbulent motions responsible for momentum transport. One nominally pertains to the shape of the relevant motions as quantified by their area coverage in any given wall-parallel plane, and the other pertains to the changing size of these motions in the wall-normal direction. In accord with self-similar mean dynamics, these two features remain invariant across the inertial domain. Data from direct numerical simulations and higher Reynolds number experiments are presented and discussed relative to the self-similar geometric structure indicated by the analysis, and in particular the special form of self-similarity

  12. Structural investigation of a novel heteropolysaccharide from the fruiting bodies of Boletus edulis.

    Science.gov (United States)

    Zhang, An-qiang; Liu, Ye; Xiao, Nan-nan; Zhang, Yang; Sun, Pei-long

    2014-03-01

    A novel water-soluble heteropolysaccharide, BEPF1, was isolated from the fruiting bodies of Boletus edulis with boiling water extraction and purified by Sephacryl S-300, with a molecular weight of 1.08×10(4)Da. Sugar composition of BEPF1 showed that it was composed of l-fucose, d-mannose, d-glucose and d-galactose in the ratio of 0.21:0.23:1.17:1.00. Methylation analysis together with (1)H, (13)C and 2D NMR spectroscopy established that BEPF1 was consisted of α-d-(1→6)-galactopyranan backbone with a terminal of α-l-fucosyl unit on O-2 of the 2-d-(2→6)-galactosyl units, β-d-(1→6)-4-O-Me-glucopyranan and β-d-(1→6)-glucopyranan backbone with a terminal β-d-glucosyl unit and it also contained a minor of 2,6-β-d-Mannopyranan residues. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  13. Similarity increases altruistic punishment in humans.

    Science.gov (United States)

    Mussweiler, Thomas; Ockenfels, Axel

    2013-11-26

    Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics--a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others' uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions.

  14. Structure based alignment and clustering of proteins (STRALCP)

    Science.gov (United States)

    Zemla, Adam T.; Zhou, Carol E.; Smith, Jason R.; Lam, Marisa W.

    2013-06-18

    Disclosed are computational methods of clustering a set of protein structures based on local and pair-wise global similarity values. Pair-wise local and global similarity values are generated based on pair-wise structural alignments for each protein in the set of protein structures. Initially, the protein structures are clustered based on pair-wise local similarity values. The protein structures are then clustered based on pair-wise global similarity values. For each given cluster both a representative structure and spans of conserved residues are identified. The representative protein structure is used to assign newly-solved protein structures to a group. The spans are used to characterize conservation and assign a "structural footprint" to the cluster.

  15. Kinetics of N-Glycan Release from Human Immunoglobulin G (IgG) by PNGase F: All Glycans Are Not Created Equal.

    Science.gov (United States)

    Huang, Yining; Orlando, Ron

    2017-12-01

    The biologic activity of IgG molecules is modulated by its crystallizable fragment N-glycosylation, and thus, the analysis of IgG glycosylation is critical. A standard approach to analyze glycosylation of IgGs involves the release of the N-glycans by the enzyme peptide N-glycosidase F, which cleaves the linkage between the asparagine residue and innermost N-acetylglucosamine (GlcNAc) of all N-glycans except those containing a 3-linked fucose attached to the reducing terminal GlcNAc residue. The importance of obtaining complete glycan release for accurate quantitation led us to investigate the kinetics of this de-glycosylation reaction for IgG glycopeptides and to determine the effect of glycan structure and amino acid sequence on the rate of glycan release from glycopeptides of IgGs. This study revealed that the slight differences in amino acid sequences did not lead to a statistically different deglycosylation rate. However, statistically significant differences in the deglycosylation rate constants were observed between glycopeptides differing only in glycan structure ( i.e. , nonfucosylated, fucosylated, bisecting-GlcNAc, sialylated, etc .). For example, a single sialic acid residue was found to decrease the rate by a factor of 3. Similar reductions in rate were associated with the presence of a bisecting-GlcNAc. We predict the differences in release kinetics can lead to significant quantitative variations of the glycosylation study of IgGs.

  16. Prosodic Similarity Effects in Short-Term Memory in Developmental Dyslexia.

    Science.gov (United States)

    Goswami, Usha; Barnes, Lisa; Mead, Natasha; Power, Alan James; Leong, Victoria

    2016-11-01

    Children with developmental dyslexia are characterized by phonological difficulties across languages. Classically, this 'phonological deficit' in dyslexia has been investigated with tasks using single-syllable words. Recently, however, several studies have demonstrated difficulties in prosodic awareness in dyslexia. Potential prosodic effects in short-term memory have not yet been investigated. Here we create a new instrument based on three-syllable words that vary in stress patterns, to investigate whether prosodic similarity (the same prosodic pattern of stressed and unstressed syllables) exerts systematic effects on short-term memory. We study participants with dyslexia and age-matched and younger reading-level-matched typically developing controls. We find that all participants, including dyslexic participants, show prosodic similarity effects in short-term memory. All participants exhibited better retention of words that differed in prosodic structure, although participants with dyslexia recalled fewer words accurately overall compared to age-matched controls. Individual differences in prosodic memory were predicted by earlier vocabulary abilities, by earlier sensitivity to syllable stress and by earlier phonological awareness. To our knowledge, this is the first demonstration of prosodic similarity effects in short-term memory. The implications of a prosodic similarity effect for theories of lexical representation and of dyslexia are discussed. © 2016 The Authors. Dyslexia published by John Wiley & Sons Ltd. © 2016 The Authors. Dyslexia published by John Wiley & Sons Ltd.

  17. Computational prediction of drug-drug interactions based on drugs functional similarities.

    Science.gov (United States)

    Ferdousi, Reza; Safdari, Reza; Omidi, Yadollah

    2017-06-01

    Therapeutic activities of drugs are often influenced by co-administration of drugs that may cause inevitable drug-drug interactions (DDIs) and inadvertent side effects. Prediction and identification of DDIs are extremely vital for the patient safety and success of treatment modalities. A number of computational methods have been employed for the prediction of DDIs based on drugs structures and/or functions. Here, we report on a computational method for DDIs prediction based on functional similarity of drugs. The model was set based on key biological elements including carriers, transporters, enzymes and targets (CTET). The model was applied for 2189 approved drugs. For each drug, all the associated CTETs were collected, and the corresponding binary vectors were constructed to determine the DDIs. Various similarity measures were conducted to detect DDIs. Of the examined similarity methods, the inner product-based similarity measures (IPSMs) were found to provide improved prediction values. Altogether, 2,394,766 potential drug pairs interactions were studied. The model was able to predict over 250,000 unknown potential DDIs. Upon our findings, we propose the current method as a robust, yet simple and fast, universal in silico approach for identification of DDIs. We envision that this proposed method can be used as a practical technique for the detection of possible DDIs based on the functional similarities of drugs. Copyright © 2017. Published by Elsevier Inc.

  18. Generating "fragment-based virtual library" using pocket similarity search of ligand-receptor complexes.

    Science.gov (United States)

    Khashan, Raed S

    2015-01-01

    As the number of available ligand-receptor complexes is increasing, researchers are becoming more dedicated to mine these complexes to aid in the drug design and development process. We present free software which is developed as a tool for performing similarity search across ligand-receptor complexes for identifying binding pockets which are similar to that of a target receptor. The search is based on 3D-geometric and chemical similarity of the atoms forming the binding pocket. For each match identified, the ligand's fragment(s) corresponding to that binding pocket are extracted, thus forming a virtual library of fragments (FragVLib) that is useful for structure-based drug design. The program provides a very useful tool to explore available databases.

  19. A comprehensive comparison of network similarities for link prediction and spurious link elimination

    Science.gov (United States)

    Zhang, Peng; Qiu, Dan; Zeng, An; Xiao, Jinghua

    2018-06-01

    Identifying missing interactions in complex networks, known as link prediction, is realized by estimating the likelihood of the existence of a link between two nodes according to the observed links and nodes' attributes. Similar approaches have also been employed to identify and remove spurious links in networks which is crucial for improving the reliability of network data. In network science, the likelihood for two nodes having a connection strongly depends on their structural similarity. The key to address these two problems thus becomes how to objectively measure the similarity between nodes in networks. In the literature, numerous network similarity metrics have been proposed and their accuracy has been discussed independently in previous works. In this paper, we systematically compare the accuracy of 18 similarity metrics in both link prediction and spurious link elimination when the observed networks are very sparse or consist of inaccurate linking information. Interestingly, some methods have high prediction accuracy, they tend to perform low accuracy in identification spurious interaction. We further find that methods can be classified into several cluster according to their behaviors. This work is useful for guiding future use of these similarity metrics for different purposes.

  20. Comparative Analysis of Networks of Phonologically Similar Words in English and Spanish

    Directory of Open Access Journals (Sweden)

    Michael S. Vitevitch

    2010-03-01

    Full Text Available Previous network analyses of several languages revealed a unique set of structural characteristics. One of these characteristics—the presence of many smaller components (referred to as islands—was further examined with a comparative analysis of the island constituents. The results showed that Spanish words in the islands tended to be phonologically and semantically similar to each other, but English words in the islands tended only to be phonologically similar to each other. The results of this analysis yielded hypotheses about language processing that can be tested with psycholinguistic experiments, and offer insight into cross-language differences in processing that have been previously observed.

  1. Self-similar dynamic converging shocks - I. An isothermal gas sphere with self-gravity

    Science.gov (United States)

    Lou, Yu-Qing; Shi, Chun-Hui

    2014-07-01

    We explore novel self-similar dynamic evolution of converging spherical shocks in a self-gravitating isothermal gas under conceivable astrophysical situations. The construction of such converging shocks involves a time-reversal operation on feasible flow profiles in self-similar expansion with a proper care for the increasing direction of the specific entropy. Pioneered by Guderley since 1942 but without self-gravity so far, self-similar converging shocks are important for implosion processes in aerodynamics, combustion, and inertial fusion. Self-gravity necessarily plays a key role for grossly spherical structures in very broad contexts of astrophysics and cosmology, such as planets, stars, molecular clouds (cores), compact objects, planetary nebulae, supernovae, gamma-ray bursts, supernova remnants, globular clusters, galactic bulges, elliptical galaxies, clusters of galaxies as well as relatively hollow cavity or bubble structures on diverse spatial and temporal scales. Large-scale dynamic flows associated with such quasi-spherical systems (including collapses, accretions, fall-backs, winds and outflows, explosions, etc.) in their initiation, formation, and evolution are likely encounter converging spherical shocks at times. Our formalism lays an important theoretical basis for pertinent astrophysical and cosmological applications of various converging shock solutions and for developing and calibrating numerical codes. As examples, we describe converging shock triggered star formation, supernova explosions, and void collapses.

  2. On fuzzy semantic similarity measure for DNA coding.

    Science.gov (United States)

    Ahmad, Muneer; Jung, Low Tang; Bhuiyan, Md Al-Amin

    2016-02-01

    A coding measure scheme numerically translates the DNA sequence to a time domain signal for protein coding regions identification. A number of coding measure schemes based on numerology, geometry, fixed mapping, statistical characteristics and chemical attributes of nucleotides have been proposed in recent decades. Such coding measure schemes lack the biologically meaningful aspects of nucleotide data and hence do not significantly discriminate coding regions from non-coding regions. This paper presents a novel fuzzy semantic similarity measure (FSSM) coding scheme centering on FSSM codons׳ clustering and genetic code context of nucleotides. Certain natural characteristics of nucleotides i.e. appearance as a unique combination of triplets, preserving special structure and occurrence, and ability to own and share density distributions in codons have been exploited in FSSM. The nucleotides׳ fuzzy behaviors, semantic similarities and defuzzification based on the center of gravity of nucleotides revealed a strong correlation between nucleotides in codons. The proposed FSSM coding scheme attains a significant enhancement in coding regions identification i.e. 36-133% as compared to other existing coding measure schemes tested over more than 250 benchmarked and randomly taken DNA datasets of different organisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs.

    Science.gov (United States)

    Smit, Cornelis H; van Diepen, Angela; Nguyen, D Linh; Wuhrer, Manfred; Hoffmann, Karl F; Deelder, André M; Hokke, Cornelis H

    2015-07-01

    Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1-4(Fucα1-3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1-3(Galβ1-6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated

  4. Quantitative analysis of N-glycans from human alfa-acid-glycoprotein using stable isotope labeling and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry as tool for pancreatic disease diagnosis

    International Nuclear Information System (INIS)

    Giménez, Estela; Balmaña, Meritxell; Figueras, Joan; Fort, Esther; Bolós, Carme de; Sanz-Nebot, Victòria; Peracaula, Rosa; Rizzi, Andreas

    2015-01-01

    Highlights: • The method enables relative quantitation of hAGP glycans from pathological samples • Pancreatic cancer samples clearly showed an increase of hAGP fucosylated glycans. • Fucosylated glycans could be potential biomarkers for diagnosing pancreatic cancer. • The established method could be extremely useful to find novel glycoprotein biomarkers - Abstract: In this work we demonstrate the potential of glycan reductive isotope labeling (GRIL) using [ 12 C]- and [ 13 C]-coded aniline and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry (μZIC-HILIC-ESI-MS) for relative quantitation of glycosylation variants in selected glycoproteins present in samples from cancer patients. Human α 1 -acid-glycoprotein (hAGP) is an acute phase serum glycoprotein whose glycosylation has been described to be altered in cancer and chronic inflammation. However, it is not clear yet whether some particular glycans in hAGP can be used as biomarker for differentiating between these two pathologies. In this work, hAGP was isolated by immunoaffinity chromatography (IAC) from serum samples of healthy individuals and from those suffering chronic pancreatitis and different stages of pancreatic cancer, respectively. After de-N-glycosylation, relative quantitation of the hAGP glycans was carried out using stable isotope labeling and μZIC-HILIC-ESI-MS analysis. First, protein denaturing conditions prior to PNGase F digestion were optimized to achieve quantitative digestion yields, and the reproducibility of the established methodology was evaluated with standard hAGP. Then, the proposed method was applied to the analysis of the clinical samples (control vs. pathological). Pancreatic cancer samples clearly showed an increase in the abundance of fucosylated glycans as the stage of the disease increases and this was unlike to samples from chronic pancreatitis. The results gained here indicate the mentioned glycan in hAGP as a

  5. Detecting earthquakes over a seismic network using single-station similarity measures

    Science.gov (United States)

    Bergen, Karianne J.; Beroza, Gregory C.

    2018-06-01

    New blind waveform-similarity-based detection methods, such as Fingerprint and Similarity Thresholding (FAST), have shown promise for detecting weak signals in long-duration, continuous waveform data. While blind detectors are capable of identifying similar or repeating waveforms without templates, they can also be susceptible to false detections due to local correlated noise. In this work, we present a set of three new methods that allow us to extend single-station similarity-based detection over a seismic network; event-pair extraction, pairwise pseudo-association, and event resolution complete a post-processing pipeline that combines single-station similarity measures (e.g. FAST sparse similarity matrix) from each station in a network into a list of candidate events. The core technique, pairwise pseudo-association, leverages the pairwise structure of event detections in its network detection model, which allows it to identify events observed at multiple stations in the network without modeling the expected moveout. Though our approach is general, we apply it to extend FAST over a sparse seismic network. We demonstrate that our network-based extension of FAST is both sensitive and maintains a low false detection rate. As a test case, we apply our approach to 2 weeks of continuous waveform data from five stations during the foreshock sequence prior to the 2014 Mw 8.2 Iquique earthquake. Our method identifies nearly five times as many events as the local seismicity catalogue (including 95 per cent of the catalogue events), and less than 1 per cent of these candidate events are false detections.

  6. Testing Self-Similarity Through Lamperti Transformations

    KAUST Repository

    Lee, Myoungji

    2016-07-14

    Self-similar processes have been widely used in modeling real-world phenomena occurring in environmetrics, network traffic, image processing, and stock pricing, to name but a few. The estimation of the degree of self-similarity has been studied extensively, while statistical tests for self-similarity are scarce and limited to processes indexed in one dimension. This paper proposes a statistical hypothesis test procedure for self-similarity of a stochastic process indexed in one dimension and multi-self-similarity for a random field indexed in higher dimensions. If self-similarity is not rejected, our test provides a set of estimated self-similarity indexes. The key is to test stationarity of the inverse Lamperti transformations of the process. The inverse Lamperti transformation of a self-similar process is a strongly stationary process, revealing a theoretical connection between the two processes. To demonstrate the capability of our test, we test self-similarity of fractional Brownian motions and sheets, their time deformations and mixtures with Gaussian white noise, and the generalized Cauchy family. We also apply the self-similarity test to real data: annual minimum water levels of the Nile River, network traffic records, and surface heights of food wrappings. © 2016, International Biometric Society.

  7. Low alloy steel versus ADI – differences and similarities

    Directory of Open Access Journals (Sweden)

    A. Krzyńska

    2009-01-01

    Full Text Available The results of comparison between the microstructure of selected bainitic low alloy steel and austempered ductile iron ADI are presented. The aim of the comparison was to find out differences and similarities existing in these iron carbon commercial alloys. In this paper our own results on ADI structure and literature data were used. It follows from discussion presented here that both microstructure and properties of ADI are very close that which are observed in low alloy carbon steel. Moreover, we suggest that there is no so doubt to treat ADI mechanical properties as steel containing nodular inclusions of graphite.

  8. Activation analysis. A basis for chemical similarity and classification

    Energy Technology Data Exchange (ETDEWEB)

    Beeck, J OP de [Ghent Rijksuniversiteit (Belgium). Instituut voor Kernwetenschappen

    1977-01-01

    It is shown that activation analysis is especially suited to serve as a basis for determining the chemical similarity between samples defined by their trace-element concentration patterns. The general problem of classification and identification is discussed. The nature of possible classification structures and their appropriate clustering strategies is considered. A practical computer method is suggested and its application as well as the graphical representation of classification results are given. The possibility for classification using information theory is mentioned. Classification of chemical elements is discussed and practically realized after Hadamard transformation of the concentration variation patterns in a series of samples.

  9. Soliton shock wave fronts and self-similar discontinuities in dispersion hydrodynamics

    International Nuclear Information System (INIS)

    Gurevich, A.V.; Meshcherkin, A.P.

    1987-01-01

    Nonlinear flows in nondissipative dispersion hydrodynamics are examined. It is demonstrated that in order to describe such flows it is necessary to incorporate a new concept: a special discontinuity called a ''self-similar'' discontinuity consisting of a nondissipative shock wave and a powerful slow wave discontinuity in regular hydrodynamics. The ''self similar discontinuity'' expands linearly over time. It is demonstrated that this concept may be introduced in a solution to Euler equations. The boundary conditions of the ''self similar discontinuity'' that allow closure of Euler equations for dispersion hydrodynamics are formulated, i.e., those that replace the shock adiabatic curve of standard dissipative hydrodynamics. The structure of the soliton front and of the trailing edge of the shock wave is investigated. A classification and complete solution are given to the problem of the decay of random initial discontinuities in the hydrodynamics of highly nonisothermic plasma. A solution is derived to the problem of the decay of initial discontinuities in the hydrodynamics of magnetized plasma. It is demonstrated that in this plasma, a feature of current density arises at the point of soliton inversion

  10. Right fusiform response patterns reflect visual object identity rather than semantic similarity.

    Science.gov (United States)

    Bruffaerts, Rose; Dupont, Patrick; De Grauwe, Sophie; Peeters, Ronald; De Deyne, Simon; Storms, Gerrit; Vandenberghe, Rik

    2013-12-01

    We previously reported the neuropsychological consequences of a lesion confined to the middle and posterior part of the right fusiform gyrus (case JA) causing a partial loss of knowledge of visual attributes of concrete entities in the absence of category-selectivity (animate versus inanimate). We interpreted this in the context of a two-step model that distinguishes structural description knowledge from associative-semantic processing and implicated the lesioned area in the former process. To test this hypothesis in the intact brain, multi-voxel pattern analysis was used in a series of event-related fMRI studies in a total of 46 healthy subjects. We predicted that activity patterns in this region would be determined by the identity of rather than the conceptual similarity between concrete entities. In a prior behavioral experiment features were generated for each entity by more than 1000 subjects. Based on a hierarchical clustering analysis the entities were organised into 3 semantic clusters (musical instruments, vehicles, tools). Entities were presented as words or pictures. With foveal presentation of pictures, cosine similarity between fMRI response patterns in right fusiform cortex appeared to reflect both the identity of and the semantic similarity between the entities. No such effects were found for words in this region. The effect of object identity was invariant for location, scaling, orientation axis and color (grayscale versus color). It also persisted for different exemplars referring to a same concrete entity. The apparent semantic similarity effect however was not invariant. This study provides further support for a neurobiological distinction between structural description knowledge and processing of semantic relationships and confirms the role of right mid-posterior fusiform cortex in the former process, in accordance with previous lesion evidence. © 2013.

  11. Collapse of a self-similar cylindrical scalar field with non-minimal coupling II: strong cosmic censorship

    International Nuclear Information System (INIS)

    Condron, Eoin; Nolan, Brien C

    2014-01-01

    We investigate self-similar scalar field solutions to the Einstein equations in whole cylinder symmetry. Imposing self-similarity on the spacetime gives rise to a set of single variable functions describing the metric. Furthermore, it is shown that the scalar field is dependent on a single unknown function of the same variable and that the scalar field potential has exponential form. The Einstein equations then take the form of a set of ODEs. Self-similarity also gives rise to a singularity at the scaling origin. We extend the work of Condron and Nolan (2014 Class. Quantum Grav. 31 015015), which determined the global structure of all solutions with a regular axis in the causal past of the singularity. We identified a class of solutions that evolves through the past null cone of the singularity. We give the global structure of these solutions and show that the singularity is censored in all cases. (paper)

  12. Insights into molecular recognition of LewisX mimics by DC-SIGN using NMR and molecular modelling

    International Nuclear Information System (INIS)

    Guzzi, C.; Angulo, J.; Rojo, J.; Nieto, P.M.; Doro, F.; Bernardi, A.; Thepaut, M.; Fieschi, F.; Thepaut, M.; Fieschi, F.

    2011-01-01

    In this work, we have studied in detail the binding of two α-fucosyl-amide-based mimics of Lewis X to DC-SIGN ECD (ECD = extracellular domain) using STD NMR and docking. We have concluded that the binding mode occurs mainly through the fucose moiety, in the same way as Lewis X . Similarly to other mimics containing mannose or fucose previously studied, we have shown that both compounds bind to DC-SIGN ECD in a multimodal fashion. In this case, the main contact is the interaction of two hydroxyl groups one equatorial and the other one axial (O3 and O4) of the fucose with the Ca 2+ as Lewis X and similarly to mannose-containing mimics (in this case the interacting groups are both in the equatorial position). Finally, we have measured the K D of one mimic that was 0.4 mM. Competitive STD NMR experiments indicate that the aromatic moiety provides additional binding contacts that increase the affinity. (authors)

  13. Estimating the similarity of alternative Affymetrix probe sets using transcriptional networks

    Science.gov (United States)

    2013-01-01

    Background The usefulness of the data from Affymetrix microarray analysis depends largely on the reliability of the files describing the correspondence between probe sets, genes and transcripts. Particularly, when a gene is targeted by several probe sets, these files should give information about the similarity of each alternative probe set pair. Transcriptional networks integrate the multiple correlations that exist between all probe sets and supply much more information than a simple correlation coefficient calculated for two series of signals. In this study, we used the PSAWN (Probe Set Assignment With Networks) programme we developed to investigate whether similarity of alternative probe sets resulted in some specific properties. Findings PSAWNpy delivered a full textual description of each probe set and information on the number and properties of secondary targets. PSAWNml calculated the similarity of each alternative probe set pair and allowed finding relationships between similarity and localisation of probes in common transcripts or exons. Similar alternative probe sets had very low negative correlation, high positive correlation and similar neighbourhood overlap. Using these properties, we devised a test that allowed grouping similar probe sets in a given network. By considering several networks, additional information concerning the similarity reproducibility was obtained, which allowed defining the actual similarity of alternative probe set pairs. In particular, we calculated the common localisation of probes in exons and in known transcripts and we showed that similarity was correctly correlated with them. The information collected on all pairs of alternative probe sets in the most popular 3’ IVT Affymetrix chips is available in tabular form at http://bns.crbm.cnrs.fr/download.html. Conclusions These processed data can be used to obtain a finer interpretation when comparing microarray data between biological conditions. They are particularly well

  14. Estimating the similarity of alternative Affymetrix probe sets using transcriptional networks.

    Science.gov (United States)

    Bellis, Michel

    2013-03-21

    The usefulness of the data from Affymetrix microarray analysis depends largely on the reliability of the files describing the correspondence between probe sets, genes and transcripts. Particularly, when a gene is targeted by several probe sets, these files should give information about the similarity of each alternative probe set pair. Transcriptional networks integrate the multiple correlations that exist between all probe sets and supply much more information than a simple correlation coefficient calculated for two series of signals. In this study, we used the PSAWN (Probe Set Assignment With Networks) programme we developed to investigate whether similarity of alternative probe sets resulted in some specific properties. PSAWNpy delivered a full textual description of each probe set and information on the number and properties of secondary targets. PSAWNml calculated the similarity of each alternative probe set pair and allowed finding relationships between similarity and localisation of probes in common transcripts or exons. Similar alternative probe sets had very low negative correlation, high positive correlation and similar neighbourhood overlap. Using these properties, we devised a test that allowed grouping similar probe sets in a given network. By considering several networks, additional information concerning the similarity reproducibility was obtained, which allowed defining the actual similarity of alternative probe set pairs. In particular, we calculated the common localisation of probes in exons and in known transcripts and we showed that similarity was correctly correlated with them. The information collected on all pairs of alternative probe sets in the most popular 3' IVT Affymetrix chips is available in tabular form at http://bns.crbm.cnrs.fr/download.html. These processed data can be used to obtain a finer interpretation when comparing microarray data between biological conditions. They are particularly well adapted for searching 3' alternative

  15. Panarchy: discontinuities reval similarities in the dynamic system structure of ecological and social systems

    Science.gov (United States)

    Debates on the organization, structure and dynamics of ecosystems across scales of space and time have waxed and waned in the literature for a century. From successional theory to ecosystem theories of resilience and robustness, from hierarchy to ascendency to panarchy theory, e...

  16. The Nonlocal Sparse Reconstruction Algorithm by Similarity Measurement with Shearlet Feature Vector

    Directory of Open Access Journals (Sweden)

    Wu Qidi

    2014-01-01

    Full Text Available Due to the limited accuracy of conventional methods with image restoration, the paper supplied a nonlocal sparsity reconstruction algorithm with similarity measurement. To improve the performance of restoration results, we proposed two schemes to dictionary learning and sparse coding, respectively. In the part of the dictionary learning, we measured the similarity between patches from degraded image by constructing the Shearlet feature vector. Besides, we classified the patches into different classes with similarity and trained the cluster dictionary for each class, by cascading which we could gain the universal dictionary. In the part of sparse coding, we proposed a novel optimal objective function with the coding residual item, which can suppress the residual between the estimate coding and true sparse coding. Additionally, we show the derivation of self-adaptive regularization parameter in optimization under the Bayesian framework, which can make the performance better. It can be indicated from the experimental results that by taking full advantage of similar local geometric structure feature existing in the nonlocal patches and the coding residual suppression, the proposed method shows advantage both on visual perception and PSNR compared to the conventional methods.

  17. A self-similar transformation for a dodecagonal quasiperiodic covering with T-clusters

    International Nuclear Information System (INIS)

    Liao, Longguang; Zhang, Wenbin; Yu, Tongxu; Cao, Zexian

    2013-01-01

    A single cluster covering for the ship tiling of a dodecagonal quasiperiodic structure is obtained via a self-similar transformation, by which a turtle-like cluster, dubbed as a T-cluster, comprising seven squares, twenty regular triangles and two 30°-rhombuses, is changed into twenty scaled-down T-clusters, each centering at a vertex of the original one. Remarkably, there are three types of transformations according to the distinct configuration of the 20 scaled-down T-clusters. Detailed data for the transformations are specified. The results are expected to be helpful for the study of the physical and structural properties of dodecagonal quasicrystals. (paper)

  18. Domain similarity based orthology detection.

    Science.gov (United States)

    Bitard-Feildel, Tristan; Kemena, Carsten; Greenwood, Jenny M; Bornberg-Bauer, Erich

    2015-05-13

    Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .

  19. Measuring transferring similarity via local information

    Science.gov (United States)

    Yin, Likang; Deng, Yong

    2018-05-01

    Recommender systems have developed along with the web science, and how to measure the similarity between users is crucial for processing collaborative filtering recommendation. Many efficient models have been proposed (i.g., the Pearson coefficient) to measure the direct correlation. However, the direct correlation measures are greatly affected by the sparsity of dataset. In other words, the direct correlation measures would present an inauthentic similarity if two users have a very few commonly selected objects. Transferring similarity overcomes this drawback by considering their common neighbors (i.e., the intermediates). Yet, the transferring similarity also has its drawback since it can only provide the interval of similarity. To break the limitations, we propose the Belief Transferring Similarity (BTS) model. The contributions of BTS model are: (1) BTS model addresses the issue of the sparsity of dataset by considering the high-order similarity. (2) BTS model transforms uncertain interval to a certain state based on fuzzy systems theory. (3) BTS model is able to combine the transferring similarity of different intermediates using information fusion method. Finally, we compare BTS models with nine different link prediction methods in nine different networks, and we also illustrate the convergence property and efficiency of the BTS model.

  20. Self-similarity and scaling theory of complex networks

    Science.gov (United States)

    Song, Chaoming

    Scale-free networks have been studied extensively due to their relevance to many real systems as diverse as the World Wide Web (WWW), the Internet, biological and social networks. We present a novel approach to the analysis of scale-free networks, revealing that their structure is self-similar. This result is achieved by the application of a renormalization procedure which coarse-grains the system into boxes containing nodes within a given "size". Concurrently, we identify a power-law relation between the number of boxes needed to cover the network and the size of the box defining a self-similar exponent, which classifies fractal and non-fractal networks. By using the concept of renormalization as a mechanism for the growth of fractal and non-fractal modular networks, we show that the key principle that gives rise to the fractal architecture of networks is a strong effective "repulsion" between the most connected nodes (hubs) on all length scales, rendering them very dispersed. We show that a robust network comprised of functional modules, such as a cellular network, necessitates a fractal topology, suggestive of a evolutionary drive for their existence. These fundamental properties help to understand the emergence of the scale-free property in complex networks.

  1. Estimation of Cross-Lingual News Similarities Using Text-Mining Methods

    Directory of Open Access Journals (Sweden)

    Zhouhao Wang

    2018-01-01

    Full Text Available In this research, two estimation algorithms for extracting cross-lingual news pairs based on machine learning from financial news articles have been proposed. Every second, innumerable text data, including all kinds news, reports, messages, reviews, comments, and tweets are generated on the Internet, and these are written not only in English but also in other languages such as Chinese, Japanese, French, etc. By taking advantage of multi-lingual text resources provided by Thomson Reuters News, we developed two estimation algorithms for extracting cross-lingual news pairs from multilingual text resources. In our first method, we propose a novel structure that uses the word information and the machine learning method effectively in this task. Simultaneously, we developed a bidirectional Long Short-Term Memory (LSTM based method to calculate cross-lingual semantic text similarity for long text and short text, respectively. Thus, when an important news article is published, users can read similar news articles that are written in their native language using our method.

  2. Development of similarity theory for control systems

    Science.gov (United States)

    Myshlyaev, L. P.; Evtushenko, V. F.; Ivushkin, K. A.; Makarov, G. V.

    2018-05-01

    The area of effective application of the traditional similarity theory and the need necessity of its development for systems are discussed. The main statements underlying the similarity theory of control systems are given. The conditions for the similarity of control systems and the need for similarity control control are formulated. Methods and algorithms for estimating and similarity control of control systems and the results of research of control systems based on their similarity are presented. The similarity control of systems includes the current evaluation of the degree of similarity of control systems and the development of actions controlling similarity, and the corresponding targeted change in the state of any element of control systems.

  3. Survey on Sentence Similarity Evaluation using Deep Learning

    Science.gov (United States)

    Ramaprabha, J.; Das, Sayan; Mukerjee, Pronay

    2018-04-01

    Two questions asking the same thing can have di erent set of vocabulary set and syntactic structure. Which makes detecting the semantics equivalence between the sentences challenging. In online user forums like Quora, Stack Over ow, Stack Exchange, etc. its important to maintain high quality knowledge base by ensuring each unique question exists only once. Writers shouldn't have to write the same answer to each of the similar question and the reader must get a single page of the question they are looking for. For example, consider questions like What are the best ways to lose weight?, How can a person reduce weight?, and What are elective weight loss plans? to be duplicate questions because they all have the same intent.

  4. Evidence for similar early but not late representation of possible and impossible objects

    Science.gov (United States)

    Freud, Erez; Hadad, Bat-Sheva; Avidan, Galia; Ganel, Tzvi

    2015-01-01

    The perceptual processes that mediate the ability to efficiently represent object 3D structure are still not fully understood. The current study was aimed to shed light on these processes by utilizing spatially possible and impossible objects that could not be created in real 3D space. Despite being perceived as exceptionally unusual, impossible objects still possess fundamental Gestalt attributes and valid local depth cues that may support their initial successful representation. Based on this notion and on recent findings from our lab, we hypothesized that the initial representation of impossible objects would involve common mechanisms to those mediating typical object perception while the perceived differences between possible and impossible objects would emerge later along the processing hierarchy. In Experiment 1, participants preformed same/different classifications of two markers superimposed on a display containing two objects (possible or impossible). Faster reaction times were observed for displays in which the markers were superimposed on the same object (“object-based benefit”). Importantly, this benefit was similar for possible and impossible objects, suggesting that the representations of the two object categories rely on similar perceptual organization processes. Yet, responses for impossible objects were slower compared to possible objects. Experiment 2 was designed to examine the origin of this effect. Participants classified the location of two markers while exposure duration was manipulated. A similar pattern of performance was found for possible and impossible objects for the short exposure duration, with differences in accuracy between these two types of objects emerging only for longer exposure durations. Overall, these findings provide evidence that the representation of object structure relies on a multi-level process and that object impossibility selectively impairs the rendering of fine-detailed description of object structure. PMID

  5. IntelliGO: a new vector-based semantic similarity measure including annotation origin

    Directory of Open Access Journals (Sweden)

    Devignes Marie-Dominique

    2010-12-01

    Full Text Available Abstract Background The Gene Ontology (GO is a well known controlled vocabulary describing the biological process, molecular function and cellular component aspects of gene annotation. It has become a widely used knowledge source in bioinformatics for annotating genes and measuring their semantic similarity. These measures generally involve the GO graph structure, the information content of GO aspects, or a combination of both. However, only a few of the semantic similarity measures described so far can handle GO annotations differently according to their origin (i.e. their evidence codes. Results We present here a new semantic similarity measure called IntelliGO which integrates several complementary properties in a novel vector space model. The coefficients associated with each GO term that annotates a given gene or protein include its information content as well as a customized value for each type of GO evidence code. The generalized cosine similarity measure, used for calculating the dot product between two vectors, has been rigorously adapted to the context of the GO graph. The IntelliGO similarity measure is tested on two benchmark datasets consisting of KEGG pathways and Pfam domains grouped as clans, considering the GO biological process and molecular function terms, respectively, for a total of 683 yeast and human genes and involving more than 67,900 pair-wise comparisons. The ability of the IntelliGO similarity measure to express the biological cohesion of sets of genes compares favourably to four existing similarity measures. For inter-set comparison, it consistently discriminates between distinct sets of genes. Furthermore, the IntelliGO similarity measure allows the influence of weights assigned to evidence codes to be checked. Finally, the results obtained with a complementary reference technique give intermediate but correct correlation values with the sequence similarity, Pfam, and Enzyme classifications when compared to

  6. Construction of patient specific atlases from locally most similar anatomical pieces

    Science.gov (United States)

    Ramus, Liliane; Commowick, Olivier; Malandain, Grégoire

    2010-01-01

    Radiotherapy planning requires accurate delineations of the critical structures. To avoid manual contouring, atlas-based segmentation can be used to get automatic delineations. However, the results strongly depend on the chosen atlas, especially for the head and neck region where the anatomical variability is high. To address this problem, atlases adapted to the patient’s anatomy may allow for a better registration, and already showed an improvement in segmentation accuracy. However, building such atlases requires the definition of a criterion to select among a database the images that are the most similar to the patient. Moreover, the inter-expert variability of manual contouring may be high, and therefore bias the segmentation if selecting only one image for each region. To tackle these issues, we present an original method to design a piecewise most similar atlas. Given a query image, we propose an efficient criterion to select for each anatomical region the K most similar images among a database by considering local volume variations possibly induced by the tumor. Then, we present a new approach to combine the K images selected for each region into a piecewise most similar template. Our results obtained with 105 CT images of the head and neck show that our method reduces the over-segmentation seen with an average atlas while being robust to inter-expert manual segmentation variability. PMID:20879395

  7. Humans and mice express similar olfactory preferences.

    Directory of Open Access Journals (Sweden)

    Nathalie Mandairon

    Full Text Available In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.

  8. Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models.

    Science.gov (United States)

    Embry, Addie E; Liu, Zhenan; Henderson, Joel M; Byfield, F Jefferson; Liu, Liping; Yoon, Joonho; Wu, Zhenzhen; Cruz, Katrina; Moradi, Sara; Gillombardo, C Barton; Hussain, Rihanna Z; Doelger, Richard; Stuve, Olaf; Chang, Audrey N; Janmey, Paul A; Bruggeman, Leslie A; Miller, R Tyler

    2018-03-23

    Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear. Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury. Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes. Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time. Copyright © 2018 by the American Society of Nephrology.

  9. Efficient protein structure search using indexing methods.

    Science.gov (United States)

    Kim, Sungchul; Sael, Lee; Yu, Hwanjo

    2013-01-01

    Understanding functions of proteins is one of the most important challenges in many studies of biological processes. The function of a protein can be predicted by analyzing the functions of structurally similar proteins, thus finding structurally similar proteins accurately and efficiently from a large set of proteins is crucial. A protein structure can be represented as a vector by 3D-Zernike Descriptor (3DZD) which compactly represents the surface shape of the protein tertiary structure. This simplified representation accelerates the searching process. However, computing the similarity of two protein structures is still computationally expensive, thus it is hard to efficiently process many simultaneous requests of structurally similar protein search. This paper proposes indexing techniques which substantially reduce the search time to find structurally similar proteins. In particular, we first exploit two indexing techniques, i.e., iDistance and iKernel, on the 3DZDs. After that, we extend the techniques to further improve the search speed for protein structures. The extended indexing techniques build and utilize an reduced index constructed from the first few attributes of 3DZDs of protein structures. To retrieve top-k similar structures, top-10 × k similar structures are first found using the reduced index, and top-k structures are selected among them. We also modify the indexing techniques to support θ-based nearest neighbor search, which returns data points less than θ to the query point. The results show that both iDistance and iKernel significantly enhance the searching speed. In top-k nearest neighbor search, the searching time is reduced 69.6%, 77%, 77.4% and 87.9%, respectively using iDistance, iKernel, the extended iDistance, and the extended iKernel. In θ-based nearest neighbor serach, the searching time is reduced 80%, 81%, 95.6% and 95.6% using iDistance, iKernel, the extended iDistance, and the extended iKernel, respectively.

  10. QSAR and docking studies of anthraquinone derivatives by similarity cluster prediction.

    Science.gov (United States)

    Harsa, Alexandra M; Harsa, Teodora E; Diudea, Mircea V

    2016-01-01

    Forty anthraquinone derivatives have been downloaded from PubChem database and investigated in a quantitative structure-activity relationships (QSAR) study. The models describing log P and LD50 of this set were built up on the hypermolecule scheme that mimics the investigated receptor space; the models were validated by the leave-one-out procedure, in the external test set and in a new version of prediction by using similarity clusters. Molecular docking approach using Lamarckian Genetic Algorithm was made on this class of anthraquinones with respect to 3Q3B receptor. The best scored molecules in the docking assay were used as leaders in the similarity clustering procedure. It is demonstrated that the LD50 data of this set of anthraquinones are related to the binding energies of anthraquinone ligands to the 3Q3B receptor.

  11. Similar or different? The role of the ventrolateral prefrontal cortex in similarity detection.

    Directory of Open Access Journals (Sweden)

    Béatrice Garcin

    Full Text Available Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour when asked to place a banana and an orange in a single category: some patients categorize them at a concrete level (e.g., "both have peel", while others continue to look for differences between these objects (e.g., "one is yellow, the other is orange". These observations raise the question of whether abstraction and similarity detection are distinct processes involved in abstract categorization, and that depend on separate areas of the prefrontal cortex (PFC. We designed an original experimental paradigm for a functional magnetic resonance imaging (fMRI study involving healthy subjects, confirming the existence of two distinct processes relying on different prefrontal areas, and thus explaining the behavioural dissociation in frontal lesion patients. We showed that: 1 Similarity detection involves the anterior ventrolateral PFC bilaterally with a right-left asymmetry: the right anterior ventrolateral PFC is only engaged in detecting physical similarities; 2 Abstraction per se activates the left dorsolateral PFC.

  12. A Crude 1-DNJ Extract from Home Made Bombyx Batryticatus Inhibits Diabetic Cardiomyopathy-Associated Fibrosis in db/db Mice and Reduces Protein N-Glycosylation Levels

    Directory of Open Access Journals (Sweden)

    Qing Zhao

    2018-06-01

    Full Text Available The traditional Chinese drug Bombyx Batryticatus (BB, which is also named the white stiff silkworm, has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation-promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia, and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease, and to clarify the therapeutic effect of 1-Deoxynojirimycin (1-DNJ extracted from BB, we used the db/db (diabetic mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an liquid Chromatograph Mass Spectrometer (LC-MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. Advanced glycation end products (AGEs, hydroxyproline, connective tissue growth factor (CTGF, and other serum biochemical indicators were measured with enzyme-linked immunosorbent assays (ELISA. In addition, the α-1,6-fucosylation of N-glycans was profiled with lens culinaris agglutinin (LCA lectin blots and fluorescein isothiocyanate (FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α-1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α-1,6-fucosylation was significant. To verify this result, the well-known transforming growth factor-β (TGF-β/Smad2/3 pathway was selected, and core α-1,6-fucosylated TGF-β receptor II (TGFR-βII was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained

  13. Similarity from multi-dimensional scaling: solving the accuracy and diversity dilemma in information filtering.

    Directory of Open Access Journals (Sweden)

    Wei Zeng

    Full Text Available Recommender systems are designed to assist individual users to navigate through the rapidly growing amount of information. One of the most successful recommendation techniques is the collaborative filtering, which has been extensively investigated and has already found wide applications in e-commerce. One of challenges in this algorithm is how to accurately quantify the similarities of user pairs and item pairs. In this paper, we employ the multidimensional scaling (MDS method to measure the similarities between nodes in user-item bipartite networks. The MDS method can extract the essential similarity information from the networks by smoothing out noise, which provides a graphical display of the structure of the networks. With the similarity measured from MDS, we find that the item-based collaborative filtering algorithm can outperform the diffusion-based recommendation algorithms. Moreover, we show that this method tends to recommend unpopular items and increase the global diversification of the networks in long term.

  14. Similarity from multi-dimensional scaling: solving the accuracy and diversity dilemma in information filtering.

    Science.gov (United States)

    Zeng, Wei; Zeng, An; Liu, Hao; Shang, Ming-Sheng; Zhang, Yi-Cheng

    2014-01-01

    Recommender systems are designed to assist individual users to navigate through the rapidly growing amount of information. One of the most successful recommendation techniques is the collaborative filtering, which has been extensively investigated and has already found wide applications in e-commerce. One of challenges in this algorithm is how to accurately quantify the similarities of user pairs and item pairs. In this paper, we employ the multidimensional scaling (MDS) method to measure the similarities between nodes in user-item bipartite networks. The MDS method can extract the essential similarity information from the networks by smoothing out noise, which provides a graphical display of the structure of the networks. With the similarity measured from MDS, we find that the item-based collaborative filtering algorithm can outperform the diffusion-based recommendation algorithms. Moreover, we show that this method tends to recommend unpopular items and increase the global diversification of the networks in long term.

  15. Marriage Matters: Spousal Similarity in Life Satisfaction

    OpenAIRE

    Ulrich Schimmack; Richard Lucas

    2006-01-01

    Examined the concurrent and cross-lagged spousal similarity in life satisfaction over a 21-year period. Analyses were based on married couples (N = 847) in the German Socio-Economic Panel (SOEP). Concurrent spousal similarity was considerably higher than one-year retest similarity, revealing spousal similarity in the variable component of life satisfac-tion. Spousal similarity systematically decreased with length of retest interval, revealing simi-larity in the changing component of life sati...

  16. Information filtering based on transferring similarity.

    Science.gov (United States)

    Sun, Duo; Zhou, Tao; Liu, Jian-Guo; Liu, Run-Ran; Jia, Chun-Xiao; Wang, Bing-Hong

    2009-07-01

    In this Brief Report, we propose an index of user similarity, namely, the transferring similarity, which involves all high-order similarities between users. Accordingly, we design a modified collaborative filtering algorithm, which provides remarkably higher accurate predictions than the standard collaborative filtering. More interestingly, we find that the algorithmic performance will approach its optimal value when the parameter, contained in the definition of transferring similarity, gets close to its critical value, before which the series expansion of transferring similarity is convergent and after which it is divergent. Our study is complementary to the one reported in [E. A. Leicht, P. Holme, and M. E. J. Newman, Phys. Rev. E 73, 026120 (2006)], and is relevant to the missing link prediction problem.

  17. Characterizing Chemical Similarity with Vibrational Spectroscopy: New Insights into the Substituent Effects in Monosubstituted Benzenes.

    Science.gov (United States)

    Tao, Yunwen; Zou, Wenli; Cremer, Dieter; Kraka, Elfi

    2017-10-26

    A novel approach is presented to assess chemical similarity based the local vibrational mode analysis developed by Konkoli and Cremer. The local mode frequency shifts are introduced as similarity descriptors that are sensitive to any electronic structure change. In this work, 59 different monosubstituted benzenes are compared. For a subset of 43 compounds, for which experimental data was available, the ortho-/para- and meta-directing effect in electrophilic aromatic substitution reactions could be correctly reproduced, proving the robustness of the new similarity index. For the remaining 16 compounds, the directing effect was predicted. The new approach is broadly applicable to all compounds for which either experimental or calculated vibrational frequency information is available.

  18. Investigation of psychophysical similarity measures for selection of similar images in the diagnosis of clustered microcalcifications on mammograms

    International Nuclear Information System (INIS)

    Muramatsu, Chisako; Li Qiang; Schmidt, Robert; Shiraishi, Junji; Doi, Kunio

    2008-01-01

    The presentation of images with lesions of known pathology that are similar to an unknown lesion may be helpful to radiologists in the diagnosis of challenging cases for improving the diagnostic accuracy and also for reducing variation among different radiologists. The authors have been developing a computerized scheme for automatically selecting similar images with clustered microcalcifications on mammograms from a large database. For similar images to be useful, they must be similar from the point of view of the diagnosing radiologists. In order to select such images, subjective similarity ratings were obtained for a number of pairs of clustered microcalcifications by breast radiologists for establishment of a ''gold standard'' of image similarity, and the gold standard was employed for determination and evaluation of the selection of similar images. The images used in this study were obtained from the Digital Database for Screening Mammography developed by the University of South Florida. The subjective similarity ratings for 300 pairs of images with clustered microcalcifications were determined by ten breast radiologists. The authors determined a number of image features which represent the characteristics of clustered microcalcifications that radiologists would use in their diagnosis. For determination of objective similarity measures, an artificial neural network (ANN) was employed. The ANN was trained with the average subjective similarity ratings as teacher and selected image features as input data. The ANN was trained to learn the relationship between the image features and the radiologists' similarity ratings; therefore, once the training was completed, the ANN was able to determine the similarity, called a psychophysical similarity measure, which was expected to be close to radiologists' impressions, for an unknown pair of clustered microcalcifications. By use of a leave-one-out test method, the best combination of features was selected. The correlation

  19. Investigation of psychophysical similarity measures for selection of similar images in the diagnosis of clustered microcalcifications on mammograms

    Energy Technology Data Exchange (ETDEWEB)

    Muramatsu, Chisako; Li Qiang; Schmidt, Robert; Shiraishi, Junji; Doi, Kunio [Department of Radiology, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States) and Department of Intelligent Image Information, Gifu University, 1-1 Yanagido, Gifu (Japan); Department of Radiology, Duke Advanced Imaging Labs, Duke University, 2424 Erwin Road, Suite 302, Durham, North Carolina 27705 (United States); Department of Radiology, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States)

    2008-12-15

    The presentation of images with lesions of known pathology that are similar to an unknown lesion may be helpful to radiologists in the diagnosis of challenging cases for improving the diagnostic accuracy and also for reducing variation among different radiologists. The authors have been developing a computerized scheme for automatically selecting similar images with clustered microcalcifications on mammograms from a large database. For similar images to be useful, they must be similar from the point of view of the diagnosing radiologists. In order to select such images, subjective similarity ratings were obtained for a number of pairs of clustered microcalcifications by breast radiologists for establishment of a ''gold standard'' of image similarity, and the gold standard was employed for determination and evaluation of the selection of similar images. The images used in this study were obtained from the Digital Database for Screening Mammography developed by the University of South Florida. The subjective similarity ratings for 300 pairs of images with clustered microcalcifications were determined by ten breast radiologists. The authors determined a number of image features which represent the characteristics of clustered microcalcifications that radiologists would use in their diagnosis. For determination of objective similarity measures, an artificial neural network (ANN) was employed. The ANN was trained with the average subjective similarity ratings as teacher and selected image features as input data. The ANN was trained to learn the relationship between the image features and the radiologists' similarity ratings; therefore, once the training was completed, the ANN was able to determine the similarity, called a psychophysical similarity measure, which was expected to be close to radiologists' impressions, for an unknown pair of clustered microcalcifications. By use of a leave-one-out test method, the best combination of features

  20. On the measurements of molecular similarity: a connection between quantum chemistry and artificial intelligence

    International Nuclear Information System (INIS)

    Carbo, R.; Calabuig, B.

    1988-01-01

    Molecular similarity measures within the quantum concept of density functions are described and analyzed. It is intended to show how artificial intelligence techniques can be used within the framework of quantum theory, in order to study and classify the molecular structures and their properties. (A.C.A.S) [pt

  1. Similar speaker recognition using nonlinear analysis

    International Nuclear Information System (INIS)

    Seo, J.P.; Kim, M.S.; Baek, I.C.; Kwon, Y.H.; Lee, K.S.; Chang, S.W.; Yang, S.I.

    2004-01-01

    Speech features of the conventional speaker identification system, are usually obtained by linear methods in spectral space. However, these methods have the drawback that speakers with similar voices cannot be distinguished, because the characteristics of their voices are also similar in spectral space. To overcome the difficulty in linear methods, we propose to use the correlation exponent in the nonlinear space as a new feature vector for speaker identification among persons with similar voices. We show that our proposed method surprisingly reduces the error rate of speaker identification system to speakers with similar voices

  2. Differences in Cellulosic Supramolecular Structure of Compositionally Similar Rice Straw Affect Biomass Metabolism by Paddy Soil Microbiota.

    Directory of Open Access Journals (Sweden)

    Tatsuki Ogura

    Full Text Available Because they are strong and stable, lignocellulosic supramolecular structures in plant cell walls are resistant to decomposition. However, they can be degraded and recycled by soil microbiota. Little is known about the biomass degradation profiles of complex microbiota based on differences in cellulosic supramolecular structures without compositional variations. Here, we characterized and evaluated the cellulosic supramolecular structures and composition of rice straw biomass processed under different milling conditions. We used a range of techniques including solid- and solution-state nuclear magnetic resonance (NMR and Fourier transform infrared spectroscopy followed by thermodynamic and microbial degradability characterization using thermogravimetric analysis, solution-state NMR, and denaturing gradient gel electrophoresis. These measured data were further analyzed using an "ECOMICS" web-based toolkit. From the results, we found that physical pretreatment of rice straw alters the lignocellulosic supramolecular structure by cleaving significant molecular lignocellulose bonds. The transformation from crystalline to amorphous cellulose shifted the thermal degradation profiles to lower temperatures. In addition, pretreated rice straw samples developed different microbiota profiles with different metabolic dynamics during the biomass degradation process. This is the first report to comprehensively characterize the structure, composition, and thermal degradation and microbiota profiles using the ECOMICS toolkit. By revealing differences between lignocellulosic supramolecular structures of biomass processed under different milling conditions, our analysis revealed how the characteristic compositions of microbiota profiles develop in addition to their metabolic profiles and dynamics during biomass degradation.

  3. Dynamic similarity in erosional processes

    Science.gov (United States)

    Scheidegger, A.E.

    1963-01-01

    A study is made of the dynamic similarity conditions obtaining in a variety of erosional processes. The pertinent equations for each type of process are written in dimensionless form; the similarity conditions can then easily be deduced. The processes treated are: raindrop action, slope evolution and river erosion. ?? 1963 Istituto Geofisico Italiano.

  4. Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile

    Science.gov (United States)

    Thanabalasingham, Gaya; Huffman, Jennifer E.; Kattla, Jayesh J.; Novokmet, Mislav; Rudan, Igor; Gloyn, Anna L.; Hayward, Caroline; Adamczyk, Barbara; Reynolds, Rebecca M.; Muzinic, Ana; Hassanali, Neelam; Pucic, Maja; Bennett, Amanda J.; Essafi, Abdelkader; Polasek, Ozren; Mughal, Saima A.; Redzic, Irma; Primorac, Dragan; Zgaga, Lina; Kolcic, Ivana; Hansen, Torben; Gasperikova, Daniela; Tjora, Erling; Strachan, Mark W.J.; Nielsen, Trine; Stanik, Juraj; Klimes, Iwar; Pedersen, Oluf B.; Njølstad, Pål R.; Wild, Sarah H.; Gyllensten, Ulf; Gornik, Olga; Wilson, James F.; Hastie, Nicholas D.; Campbell, Harry; McCarthy, Mark I.; Rudd, Pauline M.; Owen, Katharine R.; Lauc, Gordan; Wright, Alan F.

    2013-01-01

    A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction. PMID:23274891

  5. Contrasting lexical similarity and formal definitions in SNOMED CT: consistency and implications.

    Science.gov (United States)

    Agrawal, Ankur; Elhanan, Gai

    2014-02-01

    To quantify the presence of and evaluate an approach for detection of inconsistencies in the formal definitions of SNOMED CT (SCT) concepts utilizing a lexical method. Utilizing SCT's Procedure hierarchy, we algorithmically formulated similarity sets: groups of concepts with similar lexical structure of their fully specified name. We formulated five random samples, each with 50 similarity sets, based on the same parameter: number of parents, attributes, groups, all the former as well as a randomly selected control sample. All samples' sets were reviewed for types of formal definition inconsistencies: hierarchical, attribute assignment, attribute target values, groups, and definitional. For the Procedure hierarchy, 2111 similarity sets were formulated, covering 18.1% of eligible concepts. The evaluation revealed that 38 (Control) to 70% (Different relationships) of similarity sets within the samples exhibited significant inconsistencies. The rate of inconsistencies for the sample with different relationships was highly significant compared to Control, as well as the number of attribute assignment and hierarchical inconsistencies within their respective samples. While, at this time of the HITECH initiative, the formal definitions of SCT are only a minor consideration, in the grand scheme of sophisticated, meaningful use of captured clinical data, they are essential. However, significant portion of the concepts in the most semantically complex hierarchy of SCT, the Procedure hierarchy, are modeled inconsistently in a manner that affects their computability. Lexical methods can efficiently identify such inconsistencies and possibly allow for their algorithmic resolution. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Protein-protein interaction inference based on semantic similarity of Gene Ontology terms.

    Science.gov (United States)

    Zhang, Shu-Bo; Tang, Qiang-Rong

    2016-07-21

    Identifying protein-protein interactions is important in molecular biology. Experimental methods to this issue have their limitations, and computational approaches have attracted more and more attentions from the biological community. The semantic similarity derived from the Gene Ontology (GO) annotation has been regarded as one of the most powerful indicators for protein interaction. However, conventional methods based on GO similarity fail to take advantage of the specificity of GO terms in the ontology graph. We proposed a GO-based method to predict protein-protein interaction by integrating different kinds of similarity measures derived from the intrinsic structure of GO graph. We extended five existing methods to derive the semantic similarity measures from the descending part of two GO terms in the GO graph, then adopted a feature integration strategy to combines both the ascending and the descending similarity scores derived from the three sub-ontologies to construct various kinds of features to characterize each protein pair. Support vector machines (SVM) were employed as discriminate classifiers, and five-fold cross validation experiments were conducted on both human and yeast protein-protein interaction datasets to evaluate the performance of different kinds of integrated features, the experimental results suggest the best performance of the feature that combines information from both the ascending and the descending parts of the three ontologies. Our method is appealing for effective prediction of protein-protein interaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Trajectory similarity join in spatial networks

    KAUST Repository

    Shang, Shuo

    2017-09-07

    The matching of similar pairs of objects, called similarity join, is fundamental functionality in data management. We consider the case of trajectory similarity join (TS-Join), where the objects are trajectories of vehicles moving in road networks. Thus, given two sets of trajectories and a threshold θ, the TS-Join returns all pairs of trajectories from the two sets with similarity above θ. This join targets applications such as trajectory near-duplicate detection, data cleaning, ridesharing recommendation, and traffic congestion prediction. With these applications in mind, we provide a purposeful definition of similarity. To enable efficient TS-Join processing on large sets of trajectories, we develop search space pruning techniques and take into account the parallel processing capabilities of modern processors. Specifically, we present a two-phase divide-and-conquer algorithm. For each trajectory, the algorithm first finds similar trajectories. Then it merges the results to achieve a final result. The algorithm exploits an upper bound on the spatiotemporal similarity and a heuristic scheduling strategy for search space pruning. The algorithm\\'s per-trajectory searches are independent of each other and can be performed in parallel, and the merging has constant cost. An empirical study with real data offers insight in the performance of the algorithm and demonstrates that is capable of outperforming a well-designed baseline algorithm by an order of magnitude.

  8. What Can We Learn from Similar Male Dominated Industries?

    International Nuclear Information System (INIS)

    Thomas, C.

    2015-01-01

    Thomas Thor Associates is an Executive Recruitment company solely dedicated to the Nuclear industry. We have been involved with WiN UK in 2014–2015 to help them develop their own organization, this research was part of our partnership. The main purpose of this paper is to provide a clear picture of the techniques that are used by organizations similar to WiN, and business in other industries that are similar to Nuclear, to attract more women to pursue a career in a particular industry, and to support retention and career progression of women in these industries. This paper has taken a look at all industries that require technical and engineering staff, after which the Mining, Oil & Gas, Petro-chemicals, Rail, Renewable Energy, Technology and Construction industries were found to show most similarities with Nuclear, in terms of the technical staff required and their structure on gender diversity. From here, case studies of industry organizations and professional business have been prepared in order to inform WiN of best practice in these industries and provide a benchmark for future WiN operations. Finally, the report results into giving recommendations on projects WiN could add to their current approach to achieve their objectives. The recommendations are based on the results from the case studies, focusing on attracting, recruiting, retaining and developing female professionals. In summary, the recommendations are to: highlight potential career paths for women in Nuclear, educate women on Nuclear, support the development of women and to help companies to increase their bottom line by getting WiN certified. (author)

  9. Atomic structure in black hole

    International Nuclear Information System (INIS)

    Nagatani, Yukinori

    2006-01-01

    We propose that any black hole has atomic structure in its inside and has no horizon as a model of black holes. Our proposal is founded on a mean field approximation of gravity. The structure of our model consists of a (charged) singularity at the center and quantum fluctuations of fields around the singularity, namely, it is quite similar to that of atoms. Any properties of black holes, e.g. entropy, can be explained by the model. The model naturally quantizes black holes. In particular, we find the minimum black hole, whose structure is similar to that of the hydrogen atom and whose Schwarzschild radius is approximately 1.1287 times the Planck length. Our approach is conceptually similar to Bohr's model of the atomic structure, and the concept of the minimum Schwarzschild radius is similar to that of the Bohr radius. The model predicts that black holes carry baryon number, and the baryon number is rapidly violated. This baryon number violation can be used as verification of the model. (author)

  10. On self-similar Tolman models

    International Nuclear Information System (INIS)

    Maharaj, S.D.

    1988-01-01

    The self-similar spherically symmetric solutions of the Einstein field equation for the case of dust are identified. These form a subclass of the Tolman models. These self-similar models contain the solution recently presented by Chi [J. Math. Phys. 28, 1539 (1987)], thereby refuting the claim of having found a new solution to the Einstein field equations

  11. The next generation of similarity measures that fully explore the semantics in biomedical ontologies.

    Science.gov (United States)

    Couto, Francisco M; Pinto, H Sofia

    2013-10-01

    There is a prominent trend to augment and improve the formality of biomedical ontologies. For example, this is shown by the current effort on adding description logic axioms, such as disjointness. One of the key ontology applications that can take advantage of this effort is the conceptual (functional) similarity measurement. The presence of description logic axioms in biomedical ontologies make the current structural or extensional approaches weaker and further away from providing sound semantics-based similarity measures. Although beneficial in small ontologies, the exploration of description logic axioms by semantics-based similarity measures is computational expensive. This limitation is critical for biomedical ontologies that normally contain thousands of concepts. Thus in the process of gaining their rightful place, biomedical functional similarity measures have to take the journey of finding how this rich and powerful knowledge can be fully explored while keeping feasible computational costs. This manuscript aims at promoting and guiding the development of compelling tools that deliver what the biomedical community will require in a near future: a next-generation of biomedical similarity measures that efficiently and fully explore the semantics present in biomedical ontologies.

  12. DOSim: An R package for similarity between diseases based on Disease Ontology

    Science.gov (United States)

    2011-01-01

    Background The construction of the Disease Ontology (DO) has helped promote the investigation of diseases and disease risk factors. DO enables researchers to analyse disease similarity by adopting semantic similarity measures, and has expanded our understanding of the relationships between different diseases and to classify them. Simultaneously, similarities between genes can also be analysed by their associations with similar diseases. As a result, disease heterogeneity is better understood and insights into the molecular pathogenesis of similar diseases have been gained. However, bioinformatics tools that provide easy and straight forward ways to use DO to study disease and gene similarity simultaneously are required. Results We have developed an R-based software package (DOSim) to compute the similarity between diseases and to measure the similarity between human genes in terms of diseases. DOSim incorporates a DO-based enrichment analysis function that can be used to explore the disease feature of an independent gene set. A multilayered enrichment analysis (GO and KEGG annotation) annotation function that helps users explore the biological meaning implied in a newly detected gene module is also part of the DOSim package. We used the disease similarity application to demonstrate the relationship between 128 different DO cancer terms. The hierarchical clustering of these 128 different cancers showed modular characteristics. In another case study, we used the gene similarity application on 361 obesity-related genes. The results revealed the complex pathogenesis of obesity. In addition, the gene module detection and gene module multilayered annotation functions in DOSim when applied on these 361 obesity-related genes helped extend our understanding of the complex pathogenesis of obesity risk phenotypes and the heterogeneity of obesity-related diseases. Conclusions DOSim can be used to detect disease-driven gene modules, and to annotate the modules for functions and

  13. SimShiftDB; local conformational restraints derived from chemical shift similarity searches on a large synthetic database

    Energy Technology Data Exchange (ETDEWEB)

    Ginzinger, Simon W. [Center of Applied Molecular Engineering, University of Salzburg, Department of Molecular Biology, Division of Bioinformatics (Austria)], E-mail: simon@came.sbg.ac.at; Coles, Murray [Max-Planck-Institute for Developmental Biology, Department of Protein Evolution (Germany)], E-mail: Murray.Coles@tuebingen.mpg.de

    2009-03-15

    We present SimShiftDB, a new program to extract conformational data from protein chemical shifts using structural alignments. The alignments are obtained in searches of a large database containing 13,000 structures and corresponding back-calculated chemical shifts. SimShiftDB makes use of chemical shift data to provide accurate results even in the case of low sequence similarity, and with even coverage of the conformational search space. We compare SimShiftDB to HHSearch, a state-of-the-art sequence-based search tool, and to TALOS, the current standard tool for the task. We show that for a significant fraction of the predicted similarities, SimShiftDB outperforms the other two methods. Particularly, the high coverage afforded by the larger database often allows predictions to be made for residues not involved in canonical secondary structure, where TALOS predictions are both less frequent and more error prone. Thus SimShiftDB can be seen as a complement to currently available methods.

  14. SimShiftDB; local conformational restraints derived from chemical shift similarity searches on a large synthetic database

    International Nuclear Information System (INIS)

    Ginzinger, Simon W.; Coles, Murray

    2009-01-01

    We present SimShiftDB, a new program to extract conformational data from protein chemical shifts using structural alignments. The alignments are obtained in searches of a large database containing 13,000 structures and corresponding back-calculated chemical shifts. SimShiftDB makes use of chemical shift data to provide accurate results even in the case of low sequence similarity, and with even coverage of the conformational search space. We compare SimShiftDB to HHSearch, a state-of-the-art sequence-based search tool, and to TALOS, the current standard tool for the task. We show that for a significant fraction of the predicted similarities, SimShiftDB outperforms the other two methods. Particularly, the high coverage afforded by the larger database often allows predictions to be made for residues not involved in canonical secondary structure, where TALOS predictions are both less frequent and more error prone. Thus SimShiftDB can be seen as a complement to currently available methods

  15. Phonological similarity and orthographic similarity affect probed serial recall of Chinese characters.

    Science.gov (United States)

    Lin, Yi-Chen; Chen, Hsiang-Yu; Lai, Yvonne C; Wu, Denise H

    2015-04-01

    The previous literature on working memory (WM) has indicated that verbal materials are dominantly retained in phonological representations, whereas other linguistic information (e.g., orthography, semantics) only contributes to verbal WM minimally, if not negligibly. Although accumulating evidence has suggested that multiple linguistic components jointly support verbal WM, the visual/orthographic contribution has rarely been addressed in alphabetic languages, possibly due to the difficulty of dissociating the effects of word forms from the effects of their pronunciations in relatively shallow orthography. In the present study, we examined whether the orthographic representations of Chinese characters support the retention of verbal materials in this language of deep orthography. In Experiments 1a and 2, we independently manipulated the phonological and orthographic similarity of horizontal and vertical characters, respectively, and found that participants' accuracy of probed serial recall was reduced by both similar pronunciations and shared phonetic radicals in the to-be-remembered stimuli. Moreover, Experiment 1b showed that only the effect of phonological, but not that of orthographic, similarity was affected by concurrent articulatory suppression. Taken together, the present results indicate the indispensable contribution of orthographic representations to verbal WM of Chinese characters, and suggest that the linguistic characteristics of a specific language not only determine long-term linguistic-processing mechanisms, but also delineate the organization of verbal WM for that language.

  16. Similarity measures for face recognition

    CERN Document Server

    Vezzetti, Enrico

    2015-01-01

    Face recognition has several applications, including security, such as (authentication and identification of device users and criminal suspects), and in medicine (corrective surgery and diagnosis). Facial recognition programs rely on algorithms that can compare and compute the similarity between two sets of images. This eBook explains some of the similarity measures used in facial recognition systems in a single volume. Readers will learn about various measures including Minkowski distances, Mahalanobis distances, Hansdorff distances, cosine-based distances, among other methods. The book also summarizes errors that may occur in face recognition methods. Computer scientists "facing face" and looking to select and test different methods of computing similarities will benefit from this book. The book is also useful tool for students undertaking computer vision courses.

  17. SIMILARITY COMPARISON AND CLASSIFICATION OF SUCKING LOUSE COMMUNITIES ON SOME SMALL MAMMALS IN YUNNAN, CHINA

    Institute of Scientific and Technical Information of China (English)

    Xian-guoGuo; Ti-junQian; Li-junGuo; Wen-geDong

    2004-01-01

    The similarity and classification of sucking louse communities on 24 species of small mammals were studied in Yunnan Province, China, through a hierarchical cluster analysis. All the louse species on the body surface of a certain species of small mammals are regarded as a louse community unit. The results reveal that the community structure of sucking lice on small mammals is simple with low species diversity. Most small mammals usually have certain louse species on their body surface; there exists a high degree of host specificity. Most louse communities on the same genus of small mammals show a high similarity and are classified into the same group based on hierarchical cluster analysis. When the hosts have a close affinity in taxonomy, the louse communities on their body surface would tend to be similar with the same or similar dominant louse species (as observed in genus Rattus, Niviventer, Apodemus and Eothenomys). The similarity of sucking louse communities is highly consistent with the affinity of small mammal hosts in taxonomy. The results suggest a close relationship of co-evolution between sucking lice and their hosts.

  18. Surf similarity and solitary wave runup

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2008-01-01

    The notion of surf similarity in the runup of solitary waves is revisited. We show that the surf similarity parameter for solitary waves may be effectively reduced to the beach slope divided by the offshore wave height to depth ratio. This clarifies its physical interpretation relative to a previ...... functional dependence on their respective surf similarity parameters. Important equivalencies in the runup of sinusoidal and solitary waves are thus revealed.......The notion of surf similarity in the runup of solitary waves is revisited. We show that the surf similarity parameter for solitary waves may be effectively reduced to the beach slope divided by the offshore wave height to depth ratio. This clarifies its physical interpretation relative...... to a previous parameterization, which was not given in an explicit form. Good coherency with experimental (breaking) runup data is preserved with this simpler parameter. A recasting of analytical (nonbreaking) runup expressions for sinusoidal and solitary waves additionally shows that they contain identical...

  19. Phytoplankton distribution in three thermally different but edaphically similar reactor cooling reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Wilde, E W

    1982-01-01

    Phytoplankton community structure and the physicochemical characteristics of three reactor cooling reservoirs in close proximity and of similar age and bottom type were studied during 1978. The three reservoirs differed in thermal alteration resulting from reactor cooling water as follows: (1) considerable heating with lake-wide temperatures >30/sup 0/C, even in winter; (2) a maximal 5/sup 0/C increase occurring in only one of three major arms of the reservoir; and (3) no thermal effluent received during the study period. Considerable spatial and temporal differences in water quality and phytoplankton community structure were observed; however, water temperature independent of other environmental factors (e.g., light and nutrients) was found to be a relatively unimportant variable for explaining phytoplankton periodicity.

  20. Phytoplankton distribution in three thermally different but edaphically similar reactor cooling reservoirs

    International Nuclear Information System (INIS)

    Wilde, E.W.

    1982-01-01

    Phytoplankton community structure and the physicochemical characteristics of three reactor cooling reservoirs in close proximity and of similar age and bottom type were studied during 1978. The three reservoirs differed in thermal alteration resulting from reactor cooling water as follows: (1) considerable heating with lake-wide temperatures >30 0 C, even in winter; (2) a maximal 5 0 C increase occurring in only one of three major arms of the reservoir; and (3) no thermal effluent received during the study period. Considerable spatial and temporal differences in water quality and phytoplankton community structure were observed; however, water temperature independent of other environmental factors (e.g., light and nutrients) was found to be a relatively unimportant variable for explaining phytoplankton periodicity

  1. MicroRNA-target binding structures mimic microRNA duplex structures in humans.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    Full Text Available Traditionally, researchers match a microRNA guide strand to mRNA sequences using sequence comparisons to predict its potential target genes. However, many of the predictions can be false positives due to limitations in sequence comparison alone. In this work, we consider the association of two related RNA structures that share a common guide strand: the microRNA duplex and the microRNA-target binding structure. We have analyzed thousands of such structure pairs and found many of them share high structural similarity. Therefore, we conclude that when predicting microRNA target genes, considering just the microRNA guide strand matches to gene sequences may not be sufficient--the microRNA duplex structure formed by the guide strand and its companion passenger strand must also be considered. We have developed software to translate RNA binding structure into encoded representations, and we have also created novel automatic comparison methods utilizing such encoded representations to determine RNA structure similarity. Our software and methods can be utilized in the other RNA secondary structure comparisons as well.

  2. Significance of structure–soil–structure interaction for closely spaced structures

    International Nuclear Information System (INIS)

    Roy, Christine; Bolourchi, Said; Eggers, Daniel

    2015-01-01

    Nuclear facilities typically consist of many closely spaced structures with different sizes and depths of embedment. Seismic response of each structure could be influenced by dynamic structure–soil–structure interaction (SSSI) behavior of adjacent closely spaced structures. This paper examines the impact of SSSI on the in-structure response spectra (ISRS) and peak accelerations of a light structure adjacent to a heavy structure and of a heavy structure adjacent to a similar heavy structure for several soil cases, foundation embedment depths, and separation distances. The impacts of a heavy surface or embedded structure on adjacent ground motions were studied. The analyses demonstrated the adjacent ground motions are sensitive to foundation embedment, soil profile, response frequency, and distance from the structure. Seismic responses of a light structure located near a heavy structure are calculated either by modeling both structures subjected to free field motions, or performing a cascade analysis by considering the light structure model subjected to modified ground motions due to the heavy structure. Cascade SSSI analyses are shown to adequately account for the effect of the heavy structure on the light structure without explicitly modeling both structures together in a single analysis. To further study the influence of SSSI behavior, this paper examines dynamic response of two adjacent heavy structures and compares this response to response of a single heavy structure neglecting adjacent structures. The SSSI responses of the two heavy structures are evaluated for varying soil conditions and structure separation distances using three-dimensional linear SSI analyses and considering anti-symmetry boundary conditions. The analyses demonstrate that the SSSI response of a light or a heavy structure can be influenced by the presence of a nearby heavy structure. Although this study considers linear analysis methodology, the conclusion of SSSI influences on dynamic

  3. Design of compound libraries based on natural product scaffolds and protein structure similarity clustering (PSSC)

    NARCIS (Netherlands)

    Balamurugan, Rengarajan; Dekker, Frank J; Waldmann, Herbert; Dekker, Frans

    Recent advances in structural biology, bioinformatics and combinatorial chemistry have significantly impacted the discovery of small molecules that modulate protein functions. Natural products which have evolved to bind to proteins may serve as biologically validated starting points for the design

  4. Identifying mechanistic similarities in drug responses

    KAUST Repository

    Zhao, C.

    2012-05-15

    Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach would be to quantitate the degree of similarity between the responses that cells show when exposed to drugs, so that consistencies in the regulation of cellular response processes that produce success or failure can be more readily identified.Results: We track drug response using fluorescent proteins as transcription activity reporters. Our basic assumption is that drugs inducing very similar alteration in transcriptional regulation will produce similar temporal trajectories on many of the reporter proteins and hence be identified as having similarities in their mechanisms of action (MOA). The main body of this work is devoted to characterizing similarity in temporal trajectories/signals. To do so, we must first identify the key points that determine mechanistic similarity between two drug responses. Directly comparing points on the two signals is unrealistic, as it cannot handle delays and speed variations on the time axis. Hence, to capture the similarities between reporter responses, we develop an alignment algorithm that is robust to noise, time delays and is able to find all the contiguous parts of signals centered about a core alignment (reflecting a core mechanism in drug response). Applying the proposed algorithm to a range of real drug experiments shows that the result agrees well with the prior drug MOA knowledge. © The Author 2012. Published by Oxford University Press. All rights reserved.

  5. Similarity searching and scaffold hopping in synthetically accessible combinatorial chemistry spaces.

    Science.gov (United States)

    Boehm, Markus; Wu, Tong-Ying; Claussen, Holger; Lemmen, Christian

    2008-04-24

    Large collections of combinatorial libraries are an integral element in today's pharmaceutical industry. It is of great interest to perform similarity searches against all virtual compounds that are synthetically accessible by any such library. Here we describe the successful application of a new software tool CoLibri on 358 combinatorial libraries based on validated reaction protocols to create a single chemistry space containing over 10 (12) possible products. Similarity searching with FTrees-FS allows the systematic exploration of this space without the need to enumerate all product structures. The search result is a set of virtual hits which are synthetically accessible by one or more of the existing reaction protocols. Grouping these virtual hits by their synthetic protocols allows the rapid design and synthesis of multiple follow-up libraries. Such library ideas support hit-to-lead design efforts for tasks like follow-up from high-throughput screening hits or scaffold hopping from one hit to another attractive series.

  6. Structural region

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Structural region. The two groups had 4 substitutions similar to Yawat strain. The Yawat strain had 5 unique mutations. 3 in the E2 region and 2 in the E1 region. The mutation, I702V (E2), though different from all the recent Indian and Reunion sequences was similar ...

  7. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    DEFF Research Database (Denmark)

    Wolf, Heike; Damme, Markus; Stroobants, Stijn

    2016-01-01

    Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fuc...

  8. Predicting drug-target interaction for new drugs using enhanced similarity measures and super-target clustering.

    Science.gov (United States)

    Shi, Jian-Yu; Yiu, Siu-Ming; Li, Yiming; Leung, Henry C M; Chin, Francis Y L

    2015-07-15

    Predicting drug-target interaction using computational approaches is an important step in drug discovery and repositioning. To predict whether there will be an interaction between a drug and a target, most existing methods identify similar drugs and targets in the database. The prediction is then made based on the known interactions of these drugs and targets. This idea is promising. However, there are two shortcomings that have not yet been addressed appropriately. Firstly, most of the methods only use 2D chemical structures and protein sequences to measure the similarity of drugs and targets respectively. However, this information may not fully capture the characteristics determining whether a drug will interact with a target. Secondly, there are very few known interactions, i.e. many interactions are "missing" in the database. Existing approaches are biased towards known interactions and have no good solutions to handle possibly missing interactions which affect the accuracy of the prediction. In this paper, we enhance the similarity measures to include non-structural (and non-sequence-based) information and introduce the concept of a "super-target" to handle the problem of possibly missing interactions. Based on evaluations on real data, we show that our similarity measure is better than the existing measures and our approach is able to achieve higher accuracy than the two best existing algorithms, WNN-GIP and KBMF2K. Our approach is available at http://web.hku.hk/∼liym1018/projects/drug/drug.html or http://www.bmlnwpu.org/us/tools/PredictingDTI_S2/METHODS.html. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Similarity in Bilateral Isolated Internal Orbital Fractures.

    Science.gov (United States)

    Chen, Hung-Chang; Cox, Jacob T; Sanyal, Abanti; Mahoney, Nicholas R

    2018-04-13

    In evaluating patients sustaining bilateral isolated internal orbital fractures, the authors have observed both similar fracture locations and also similar expansion of orbital volumes. In this study, we aim to investigate if there is a propensity for the 2 orbits to fracture in symmetrically similar patterns when sustaining similar trauma. A retrospective chart review was performed studying all cases at our institution of bilateral isolated internal orbital fractures involving the medial wall and/or the floor at the time of presentation. The similarity of the bilateral fracture locations was evaluated using the Fisher's exact test. The bilateral expanded orbital volumes were analyzed using the Wilcoxon signed-rank test to assess for orbital volume similarity. Twenty-four patients with bilateral internal orbital fractures were analyzed for fracture location similarity. Seventeen patients (70.8%) had 100% concordance in the orbital subregion fractured, and the association between the right and the left orbital fracture subregion locations was statistically significant (P < 0.0001). Fifteen patients were analyzed for orbital volume similarity. The average orbital cavity volume was 31.2 ± 3.8 cm on the right and 32.0 ± 3.7 cm on the left. There was a statistically significant difference between right and left orbital cavity volumes (P = 0.0026). The data from this study suggest that an individual who suffers isolated bilateral internal orbital fractures has a statistically significant similarity in the location of their orbital fractures. However, there does not appear to be statistically significant similarity in the expansion of the orbital volumes in these patients.

  10. Personality similarity and life satisfaction in couples

    OpenAIRE

    Furler Katrin; Gomez Veronica; Grob Alexander

    2013-01-01

    The present study examined the association between personality similarity and life satisfaction in a large nationally representative sample of 1608 romantic couples. Similarity effects were computed for the Big Five personality traits as well as for personality profiles with global and differentiated indices of similarity. Results showed substantial actor and partner effects indicating that both partners' personality traits were related to both partners' life satisfaction. Personality similar...

  11. Specific binding of Ulex europaeus agglutinin I lectin to sarcolemma of distal myopathy with rimmed vacuole formation.

    Science.gov (United States)

    Yatabe, K; Kawai, M

    1997-08-01

    Ulex europaeus agglutinin I (UEA I) binding was studied in 83 patients with various neuromuscular disorders. UEA I labelled endomysial capillaries and endothelial cells of perimysial blood vessels in all the examined muscles. There was no UEA I binding to muscle fibres except for all (9) cases of distal myopathy with rimmed vacuole formation (DMRV), 1 of 5 cases of inclusion body myositis and 1 of 36 cases of inflammatory myopathies. The UEA I binding was completely eliminated by preincubation of UEA I solution with L-fucose. Using electron microscopy, the UEA I binding was localized to sarcolemma and intrasarco-plasmic membranous organelles other than mitochondria. Myosatellite cells were not labelled. These findings revealed the existence of fucosylated proteins or lipids in a subset of skeletal muscles suffering from DMRV. Biochemical identification of the fucosylated substance and further detailed study on subcellular localization of UEA I binding may yield important clues to the unknown pathogenesis of DMRV.

  12. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures.

    Science.gov (United States)

    Someswara Rao, Chinta; Viswanadha Raju, S

    2016-03-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship between the H. sapiens and monkey. This similarity will be helpful at theft identification, maternity identification, disease identification, etc.

  13. Similarity-based pattern analysis and recognition

    CERN Document Server

    Pelillo, Marcello

    2013-01-01

    This accessible text/reference presents a coherent overview of the emerging field of non-Euclidean similarity learning. The book presents a broad range of perspectives on similarity-based pattern analysis and recognition methods, from purely theoretical challenges to practical, real-world applications. The coverage includes both supervised and unsupervised learning paradigms, as well as generative and discriminative models. Topics and features: explores the origination and causes of non-Euclidean (dis)similarity measures, and how they influence the performance of traditional classification alg

  14. Object similarity affects the perceptual strategy underlying invariant visual object recognition in rats

    Directory of Open Access Journals (Sweden)

    Federica Bianca Rosselli

    2015-03-01

    Full Text Available In recent years, a number of studies have explored the possible use of rats as models of high-level visual functions. One central question at the root of such an investigation is to understand whether rat object vision relies on the processing of visual shape features or, rather, on lower-order image properties (e.g., overall brightness. In a recent study, we have shown that rats are capable of extracting multiple features of an object that are diagnostic of its identity, at least when those features are, structure-wise, distinct enough to be parsed by the rat visual system. In the present study, we have assessed the impact of object structure on rat perceptual strategy. We trained rats to discriminate between two structurally similar objects, and compared their recognition strategies with those reported in our previous study. We found that, under conditions of lower stimulus discriminability, rat visual discrimination strategy becomes more view-dependent and subject-dependent. Rats were still able to recognize the target objects, in a way that was largely tolerant (i.e., invariant to object transformation; however, the larger structural and pixel-wise similarity affected the way objects were processed. Compared to the findings of our previous study, the patterns of diagnostic features were: i smaller and more scattered; ii only partially preserved across object views; and iii only partially reproducible across rats. On the other hand, rats were still found to adopt a multi-featural processing strategy and to make use of part of the optimal discriminatory information afforded by the two objects. Our findings suggest that, as in humans, rat invariant recognition can flexibly rely on either view-invariant representations of distinctive object features or view-specific object representations, acquired through learning.

  15. Molecular moment similarity between several nucleoside analogs of thymidine and thymidine. sil@watson.ibm.com.

    Science.gov (United States)

    Silverman, B D; Pitman, M C; Platt, D E

    1999-06-01

    Molecular moment descriptors of the shape and charge distributions of twenty five nucleoside structures have been examined. The structures include thymidine as well as the difluorotoluene nucleoside analog which has been found to pair efficiently with adenine by polymerase catalysis. The remaining twenty three structures have been chosen to be as structurally similar to thymidine and to the difluorotoluene nucleoside analog as possible. The moment descriptors which include a description of the relationship of molecular charge to shape show the difluorotoluene nucleoside to be one of the most proximate molecules to thymidine in the space of the molecular moments. The calculations, therefore, suggest that polymerase specificity might be not only a consequence of molecular steric features alone but also of the molecular electrostatic environment and its registration with molecular shape.

  16. On the Isomorphism between Dissipative Systems, Fractal Self-Similarity and Electrodynamics. Toward an Integrated Vision of Nature

    Directory of Open Access Journals (Sweden)

    Giuseppe Vitiello

    2014-05-01

    Full Text Available In electrodynamics there is a mutual exchange of energy and momentum between the matter field and the electromagnetic field and the total energy and momentum are conserved. For a constant magnetic field and harmonic scalar potential, electrodynamics is shown to be isomorph to a system of damped/amplified harmonic oscillators. These can be described by squeezed coherent states which in turn are isomorph to self-similar fractal structures. Under the said conditions of constant magnetic field and harmonic scalar potential, electrodynamics is thus isomorph to fractal self-similar structures and squeezed coherent states. At a quantum level, dissipation induces noncommutative geometry with the squeezing parameter playing a relevant role. Ubiquity of fractals in Nature and relevance of coherent states and electromagnetic interaction point to a unified, integrated vision of Nature.

  17. Sound classification of dwellings in the Nordic countries – Differences and similarities between the five national schemes

    DEFF Research Database (Denmark)

    Rasmussen, Birgit

    2012-01-01

    having several similarities. In 2012, status is that number and denotations of classes for dwellings are identical in the Nordic countries, but the structures of the standards and several details are quite different. Also the issues dealt with are different. Examples of differences are sound insulation...... for classification of such buildings. This paper presents and compares the main class criteria for sound insulation of dwellings and summarizes differences and similarities in criteria and in structures of standards. Classification schemes for dwellings also exist in several other countries in Europe......In all five Nordic countries, sound classification schemes for dwellings have been published in national standards being implemented and revised gradually since the late 1990s. The national classification criteria for dwellings originate from a common Nordic INSTA-B proposal from the 1990s, thus...

  18. Large margin classification with indefinite similarities

    KAUST Repository

    Alabdulmohsin, Ibrahim; Cisse, Moustapha; Gao, Xin; Zhang, Xiangliang

    2016-01-01

    Classification with indefinite similarities has attracted attention in the machine learning community. This is partly due to the fact that many similarity functions that arise in practice are not symmetric positive semidefinite, i.e. the Mercer

  19. Quantitative analysis of N-glycans from human alfa-acid-glycoprotein using stable isotope labeling and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry as tool for pancreatic disease diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Giménez, Estela, E-mail: estelagimenez@ub.edu [Department of Analytical Chemistry, University of Barcelona, Diagonal 647, E-08028 Barcelona (Spain); Balmaña, Meritxell [Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Campus Montilivi s/n, 17071 Girona (Spain); Figueras, Joan [Department of Surgery, Dr. Josep Trueta University Hospital, IdlBGi, 17007 Girona (Spain); Fort, Esther [Digestive Unit, Dr. Josep Trueta University Hospital, 17007 Girona (Spain); Bolós, Carme de [Gastroesophagic Cancer Research Group, Research Programme in Cancer, Hospital del Mar Medical Research Institute (IMIM), Dr. Aiguader, 88, 08003 Barcelona (Spain); Sanz-Nebot, Victòria [Department of Analytical Chemistry, University of Barcelona, Diagonal 647, E-08028 Barcelona (Spain); Peracaula, Rosa [Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Campus Montilivi s/n, 17071 Girona (Spain); Rizzi, Andreas [Institute of Analytical Chemistry, University of Vienna, Währinger Straße 38, A-1090 Vienna (Austria)

    2015-03-25

    Highlights: • The method enables relative quantitation of hAGP glycans from pathological samples • Pancreatic cancer samples clearly showed an increase of hAGP fucosylated glycans. • Fucosylated glycans could be potential biomarkers for diagnosing pancreatic cancer. • The established method could be extremely useful to find novel glycoprotein biomarkers - Abstract: In this work we demonstrate the potential of glycan reductive isotope labeling (GRIL) using [{sup 12}C]- and [{sup 13}C]-coded aniline and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry (μZIC-HILIC-ESI-MS) for relative quantitation of glycosylation variants in selected glycoproteins present in samples from cancer patients. Human α{sub 1}-acid-glycoprotein (hAGP) is an acute phase serum glycoprotein whose glycosylation has been described to be altered in cancer and chronic inflammation. However, it is not clear yet whether some particular glycans in hAGP can be used as biomarker for differentiating between these two pathologies. In this work, hAGP was isolated by immunoaffinity chromatography (IAC) from serum samples of healthy individuals and from those suffering chronic pancreatitis and different stages of pancreatic cancer, respectively. After de-N-glycosylation, relative quantitation of the hAGP glycans was carried out using stable isotope labeling and μZIC-HILIC-ESI-MS analysis. First, protein denaturing conditions prior to PNGase F digestion were optimized to achieve quantitative digestion yields, and the reproducibility of the established methodology was evaluated with standard hAGP. Then, the proposed method was applied to the analysis of the clinical samples (control vs. pathological). Pancreatic cancer samples clearly showed an increase in the abundance of fucosylated glycans as the stage of the disease increases and this was unlike to samples from chronic pancreatitis. The results gained here indicate the mentioned glycan in h

  20. Engaging narratives evoke similar neural activity and lead to similar time perception.

    Science.gov (United States)

    Cohen, Samantha S; Henin, Simon; Parra, Lucas C

    2017-07-04

    It is said that we lose track of time - that "time flies" - when we are engrossed in a story. How does engagement with the story cause this distorted perception of time, and what are its neural correlates? People commit both time and attentional resources to an engaging stimulus. For narrative videos, attentional engagement can be represented as the level of similarity between the electroencephalographic responses of different viewers. Here we show that this measure of neural engagement predicted the duration of time that viewers were willing to commit to narrative videos. Contrary to popular wisdom, engagement did not distort the average perception of time duration. Rather, more similar brain responses resulted in a more uniform perception of time across viewers. These findings suggest that by capturing the attention of an audience, narrative videos bring both neural processing and the subjective perception of time into synchrony.

  1. Self-similarity in incompressible Navier-Stokes equations.

    Science.gov (United States)

    Ercan, Ali; Kavvas, M Levent

    2015-12-01

    The self-similarity conditions of the 3-dimensional (3D) incompressible Navier-Stokes equations are obtained by utilizing one-parameter Lie group of point scaling transformations. It is found that the scaling exponents of length dimensions in i = 1, 2, 3 coordinates in 3-dimensions are not arbitrary but equal for the self-similarity of 3D incompressible Navier-Stokes equations. It is also shown that the self-similarity in this particular flow process can be achieved in different time and space scales when the viscosity of the fluid is also scaled in addition to other flow variables. In other words, the self-similarity of Navier-Stokes equations is achievable under different fluid environments in the same or different gravity conditions. Self-similarity criteria due to initial and boundary conditions are also presented. Utilizing the proposed self-similarity conditions of the 3D hydrodynamic flow process, the value of a flow variable at a specified time and space can be scaled to a corresponding value in a self-similar domain at the corresponding time and space.

  2. SpolSimilaritySearch - A web tool to compare and search similarities between spoligotypes of Mycobacterium tuberculosis complex.

    Science.gov (United States)

    Couvin, David; Zozio, Thierry; Rastogi, Nalin

    2017-07-01

    Spoligotyping is one of the most commonly used polymerase chain reaction (PCR)-based methods for identification and study of genetic diversity of Mycobacterium tuberculosis complex (MTBC). Despite its known limitations if used alone, the methodology is particularly useful when used in combination with other methods such as mycobacterial interspersed repetitive units - variable number of tandem DNA repeats (MIRU-VNTRs). At a worldwide scale, spoligotyping has allowed identification of information on 103,856 MTBC isolates (corresponding to 98049 clustered strains plus 5807 unique isolates from 169 countries of patient origin) contained within the SITVIT2 proprietary database of the Institut Pasteur de la Guadeloupe. The SpolSimilaritySearch web-tool described herein (available at: http://www.pasteur-guadeloupe.fr:8081/SpolSimilaritySearch) incorporates a similarity search algorithm allowing users to get a complete overview of similar spoligotype patterns (with information on presence or absence of 43 spacers) in the aforementioned worldwide database. This tool allows one to analyze spread and evolutionary patterns of MTBC by comparing similar spoligotype patterns, to distinguish between widespread, specific and/or confined patterns, as well as to pinpoint patterns with large deleted blocks, which play an intriguing role in the genetic epidemiology of M. tuberculosis. Finally, the SpolSimilaritySearch tool also provides with the country distribution patterns for each queried spoligotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. 7 CFR 51.632 - Similar varietal characteristics.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Similar varietal characteristics. 51.632 Section 51.632 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards..., and Arizona) Definitions § 51.632 Similar varietal characteristics. Similar varietal characteristics...

  4. 7 CFR 51.694 - Similar varietal characteristics.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Similar varietal characteristics. 51.694 Section 51.694 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards..., and Arizona) Definitions § 51.694 Similar varietal characteristics. Similar varietal characteristics...

  5. Testing Self-Similarity Through Lamperti Transformations

    KAUST Repository

    Lee, Myoungji; Genton, Marc G.; Jun, Mikyoung

    2016-01-01

    extensively, while statistical tests for self-similarity are scarce and limited to processes indexed in one dimension. This paper proposes a statistical hypothesis test procedure for self-similarity of a stochastic process indexed in one dimension and multi

  6. On self-similarity of crack layer

    Science.gov (United States)

    Botsis, J.; Kunin, B.

    1987-01-01

    The crack layer (CL) theory of Chudnovsky (1986), based on principles of thermodynamics of irreversible processes, employs a crucial hypothesis of self-similarity. The self-similarity hypothesis states that the value of the damage density at a point x of the active zone at a time t coincides with that at the corresponding point in the initial (t = 0) configuration of the active zone, the correspondence being given by a time-dependent affine transformation of the space variables. In this paper, the implications of the self-similarity hypothesis for qusi-static CL propagation is investigated using polystyrene as a model material and examining the evolution of damage distribution along the trailing edge which is approximated by a straight segment perpendicular to the crack path. The results support the self-similarity hypothesis adopted by the CL theory.

  7. Predicting human age using regional morphometry and inter-regional morphological similarity

    Science.gov (United States)

    Wang, Xun-Heng; Li, Lihua

    2016-03-01

    The goal of this study is predicting human age using neuro-metrics derived from structural MRI, as well as investigating the relationships between age and predictive neuro-metrics. To this end, a cohort of healthy subjects were recruited from 1000 Functional Connectomes Project. The ages of the participations were ranging from 7 to 83 (36.17+/-20.46). The structural MRI for each subject was preprocessed using FreeSurfer, resulting in regional cortical thickness, mean curvature, regional volume and regional surface area for 148 anatomical parcellations. The individual age was predicted from the combination of regional and inter-regional neuro-metrics. The prediction accuracy is r = 0.835, p Pearson correlation coefficient between predicted ages and actual ages. Moreover, the LASSO linear regression also found certain predictive features, most of which were inter-regional features. The turning-point of the developmental trajectories in human brain was around 40 years old based on regional cortical thickness. In conclusion, structural MRI could be potential biomarkers for the aging in human brain. The human age could be successfully predicted from the combination of regional morphometry and inter-regional morphological similarity. The inter-regional measures could be beneficial to investigating human brain connectome.

  8. Multiscale coherent structures in tokamak plasma turbulence

    International Nuclear Information System (INIS)

    Xu, G. S.; Wan, B. N.; Zhang, W.; Yang, Q. W.; Wang, L.; Wen, Y. Z.

    2006-01-01

    A 12-tip poloidal probe array is used on the HT-7 superconducting tokamak [Li, Wan, and Mao, Plasma Phys. Controlled Fusion 42, 135 (2000)] to measure plasma turbulence in the edge region. Some statistical analysis techniques are used to characterize the turbulence structures. It is found that the plasma turbulence is composed of multiscale coherent structures, i.e., turbulent eddies and there is self-similarity in a relative short scale range. The presence of the self-similarity is found due to the structural similarity of these eddies between different scales. These turbulent eddies constitute the basic convection cells, so the self-similar range is just the dominant scale range relevant to transport. The experimental results also indicate that the plasma turbulence is dominated by low-frequency and long-wavelength fluctuation components and its dispersion relation shows typical electron-drift-wave characteristics. Some large-scale coherent structures intermittently burst out and exhibit a very long poloidal extent, even longer than 6 cm. It is found that these large-scale coherent structures are mainly contributed by the low-frequency and long-wavelength fluctuating components and their presence is responsible for the observations of long-range correlations, i.e., the correlation in the scale range much longer than the turbulence decorrelation scale. These experimental observations suggest that the coexistence of multiscale coherent structures results in the self-similar turbulent state

  9. 7 CFR 51.3202 - Similar varietal characteristics.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Similar varietal characteristics. 51.3202 Section 51.3202 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Similar varietal characteristics. Similar varietal characteristics means that the onions in any container...

  10. Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

    Energy Technology Data Exchange (ETDEWEB)

    Rockel, Beate [Department of Molecular Structural Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried (Germany); Schmaler, Tilo; Huang, Xiaohua [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany); Dubiel, Wolfgang, E-mail: Wolfgang.dubiel@charite.de [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany)

    2014-07-25

    Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts

  11. Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

    International Nuclear Information System (INIS)

    Rockel, Beate; Schmaler, Tilo; Huang, Xiaohua; Dubiel, Wolfgang

    2014-01-01

    Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts

  12. Self-Similar Traffic In Wireless Networks

    OpenAIRE

    Jerjomins, R.; Petersons, E.

    2005-01-01

    Many studies have shown that traffic in Ethernet and other wired networks is self-similar. This paper reveals that wireless network traffic is also self-similar and long-range dependant by analyzing big amount of data captured from the wireless router.

  13. 7 CFR 51.763 - Similar varietal characteristics.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Similar varietal characteristics. 51.763 Section 51.763 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... characteristics. Similar varietal characteristics means that the fruits in any container are similar in color and...

  14. 7 CFR 51.3057 - Similar varietal characteristics.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Similar varietal characteristics. 51.3057 Section 51.3057 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... characteristics. Similar varietal characteristics means that the avocados in any container are similar in shape...

  15. 7 CFR 51.2650 - Similar varietal characteristics.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Similar varietal characteristics. 51.2650 Section 51.2650 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... characteristics. Similar varietal characteristics means that the cherries in any container are similar in color...

  16. Correlating Structural Order with Structural Rearrangement in Dusty Plasma Liquids: Can Structural Rearrangement be Predicted by Static Structural Information?

    Science.gov (United States)

    Su, Yen-Shuo; Liu, Yu-Hsuan; I, Lin

    2012-11-01

    Whether the static microstructural order information is strongly correlated with the subsequent structural rearrangement (SR) and their predicting power for SR are investigated experimentally in the quenched dusty plasma liquid with microheterogeneities. The poor local structural order is found to be a good alarm to identify the soft spot and predict the short term SR. For the site with good structural order, the persistent time for sustaining the structural memory until SR has a large mean value but a broad distribution. The deviation of the local structural order from that averaged over nearest neighbors serves as a good second alarm to further sort out the short time SR sites. It has the similar sorting power to that using the temporal fluctuation of the local structural order over a small time interval.

  17. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures

    OpenAIRE

    Someswara Rao, Chinta; Viswanadha Raju, S.

    2016-01-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship b...

  18. The baryonic self similarity of dark matter

    International Nuclear Information System (INIS)

    Alard, C.

    2014-01-01

    The cosmological simulations indicates that dark matter halos have specific self-similar properties. However, the halo similarity is affected by the baryonic feedback. By using momentum-driven winds as a model to represent the baryon feedback, an equilibrium condition is derived which directly implies the emergence of a new type of similarity. The new self-similar solution has constant acceleration at a reference radius for both dark matter and baryons. This model receives strong support from the observations of galaxies. The new self-similar properties imply that the total acceleration at larger distances is scale-free, the transition between the dark matter and baryons dominated regime occurs at a constant acceleration, and the maximum amplitude of the velocity curve at larger distances is proportional to M 1/4 . These results demonstrate that this self-similar model is consistent with the basics of modified Newtonian dynamics (MOND) phenomenology. In agreement with the observations, the coincidence between the self-similar model and MOND breaks at the scale of clusters of galaxies. Some numerical experiments show that the behavior of the density near the origin is closely approximated by a Einasto profile.

  19. Deep absorption line studies of quiescent galaxies at z similar z ~ 2

    DEFF Research Database (Denmark)

    Toft, Sune; Gallazzi, Anna Rita; Zirm, Andrew Wasmuth

    2012-01-01

    the majority of its stars at z > 3 and currently has little or no ongoing star formation. We compile a sample of three other z similar to 2 quiescent galaxies with measured velocity dispersions, two of which are also post-starburst like. Their dynamical-mass-size relation is offset significantly less than...... the stellar-mass-size relation from the local early-type relations, which we attribute to a lower central dark matter fraction. Recent cosmological merger simulations agree qualitatively with the data, but cannot fully account for the evolution in the dark matter fraction. The z similar to 2 FP requires......We present dynamical and structural scaling relations of quiescent galaxies at z = 2, including the dynamical-mass-size relation and the first constraints on the fundamental plane (FP). The backbone of the analysis is a new, very deep Very Large Telescope/X-shooter spectrum of a massive, compact...

  20. Exploring Similarities and Differences in Personal Epistemologies of U.S. and German Elementary School Teachers

    Science.gov (United States)

    Feucht, Florian C.; Bendixen, Lisa D.

    2010-01-01

    The current study examines the personal epistemology of fourth-grade elementary school teachers from Germany (n = 10) and the United States (n = 10) to gain a more nuanced understanding of teachers' beliefs about knowledge and knowing through a cross-cultural lens. Analyses of semi-structured interviews reveal similarities and differences in the…