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Sample records for affinity maturation generates

  1. Streamlining the Pipeline for Generation of Recombinant Affinity Reagents by Integrating the Affinity Maturation Step.

    Science.gov (United States)

    Huang, Renhua; Gorman, Kevin T; Vinci, Chris R; Dobrovetsky, Elena; Gräslund, Susanne; Kay, Brian K

    2015-01-01

    Often when generating recombinant affinity reagents to a target, one singles out an individual binder, constructs a secondary library of variants, and affinity selects a tighter or more specific binder. To enhance the throughput of this general approach, we have developed a more integrated strategy where the "affinity maturation" step is part of the phage-display pipeline, rather than a follow-on process. In our new schema, we perform two rounds of affinity selection, followed by error-prone PCR on the pools of recovered clones, generation of secondary libraries, and three additional rounds of affinity selection, under conditions of off-rate competition. We demonstrate the utility of this approach by generating low nanomolar fibronectin type III (FN3) monobodies to five human proteins: ubiquitin-conjugating enzyme E2 R1 (CDC34), COP9 signalosome complex subunit 5 (COPS5), mitogen-activated protein kinase kinase 5 (MAP2K5), Splicing factor 3A subunit 1 (SF3A1) and ubiquitin carboxyl-terminal hydrolase 11 (USP11). The affinities of the resulting monobodies are typically in the single-digit nanomolar range. We demonstrate the utility of two binders by pulling down the targets from a spiked lysate of HeLa cells. This integrated approach should be applicable to directed evolution of any phage-displayed affinity reagent scaffold. PMID:26437402

  2. Streamlining the Pipeline for Generation of Recombinant Affinity Reagents by Integrating the Affinity Maturation Step

    Directory of Open Access Journals (Sweden)

    Renhua Huang

    2015-09-01

    Full Text Available Often when generating recombinant affinity reagents to a target, one singles out an individual binder, constructs a secondary library of variants, and affinity selects a tighter or more specific binder. To enhance the throughput of this general approach, we have developed a more integrated strategy where the “affinity maturation” step is part of the phage-display pipeline, rather than a follow-on process. In our new schema, we perform two rounds of affinity selection, followed by error-prone PCR on the pools of recovered clones, generation of secondary libraries, and three additional rounds of affinity selection, under conditions of off-rate competition. We demonstrate the utility of this approach by generating low nanomolar fibronectin type III (FN3 monobodies to five human proteins: ubiquitin-conjugating enzyme E2 R1 (CDC34, COP9 signalosome complex subunit 5 (COPS5, mitogen-activated protein kinase kinase 5 (MAP2K5, Splicing factor 3A subunit 1 (SF3A1 and ubiquitin carboxyl-terminal hydrolase 11 (USP11. The affinities of the resulting monobodies are typically in the single-digit nanomolar range. We demonstrate the utility of two binders by pulling down the targets from a spiked lysate of HeLa cells. This integrated approach should be applicable to directed evolution of any phage-displayed affinity reagent scaffold.

  3. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...

  4. Aptamer Affinity Maturation by Resampling and Microarray Selection.

    Science.gov (United States)

    Kinghorn, Andrew B; Dirkzwager, Roderick M; Liang, Shaolin; Cheung, Yee-Wai; Fraser, Lewis A; Shiu, Simon Chi-Chin; Tang, Marco S L; Tanner, Julian A

    2016-07-19

    Aptamers have significant potential as affinity reagents, but better approaches are critically needed to discover higher affinity nucleic acids to widen the scope for their diagnostic, therapeutic, and proteomic application. Here, we report aptamer affinity maturation, a novel aptamer enhancement technique, which combines bioinformatic resampling of aptamer sequence data and microarray selection to navigate the combinatorial chemistry binding landscape. Aptamer affinity maturation is shown to improve aptamer affinity by an order of magnitude in a single round. The novel aptamers exhibited significant adaptation, the complexity of which precludes discovery by other microarray based methods. Honing aptamer sequences using aptamer affinity maturation could help optimize a next generation of nucleic acid affinity reagents. PMID:27346322

  5. Antibody Affinity Maturation in Fishes—Our Current Understanding

    Science.gov (United States)

    Magor, Brad G.

    2015-01-01

    It has long been believed that fish lack antibody affinity maturation, in part because they were thought to lack germinal centers. Recent research done on sharks and bony fishes indicates that these early vertebrates are able to affinity mature their antibodies. This article reviews the functionality of the fish homologue of the immunoglobulin (Ig) mutator enzyme activation-induced cytidine deaminase (AID). We also consider the protein and molecular evidence for Ig somatic hypermutation and antibody affinity maturation. In the context of recent evidence for a putative proto-germinal center in fishes we propose some possible reasons that observed affinity maturation in fishes often seems lacking and propose future work that might shed further light on this process in fishes. PMID:26264036

  6. Antibody Affinity Maturation in Fishes-Our Current Understanding.

    Science.gov (United States)

    Magor, Brad G

    2015-01-01

    It has long been believed that fish lack antibody affinity maturation, in part because they were thought to lack germinal centers. Recent research done on sharks and bony fishes indicates that these early vertebrates are able to affinity mature their antibodies. This article reviews the functionality of the fish homologue of the immunoglobulin (Ig) mutator enzyme activation-induced cytidine deaminase (AID). We also consider the protein and molecular evidence for Ig somatic hypermutation and antibody affinity maturation. In the context of recent evidence for a putative proto-germinal center in fishes we propose some possible reasons that observed affinity maturation in fishes often seems lacking and propose future work that might shed further light on this process in fishes. PMID:26264036

  7. In vitro affinity maturation of a natural human antibody overcomes a barrier to in vivo affinity maturation

    Science.gov (United States)

    Li, Bing; Fouts, Ashley E; Stengel, Katharina; Luan, Peng; Dillon, Michael; Liang, Wei-Ching; Feierbach, Becket; Kelley, Robert F; Hötzel, Isidro

    2014-01-01

    Antibodies isolated from human donors are increasingly being developed for anti-infective therapeutics. These antibodies undergo affinity maturation in vivo, minimizing the need for engineering of therapeutic leads for affinity. However, the affinities required for some therapeutic applications may be higher than the affinities of the leads obtained, requiring further affinity maturation in vitro. To improve the neutralization potency of natural human antibody MSL-109 targeting human cytomegalovirus (CMV), we affinity matured the antibody against the gH/gL glycoprotein complex. A phage display library where most of the six complementary-determining regions (CDRs) were allowed to vary in only one amino acid residue at a time was used to scan for mutations that improve binding affinity. A T55R mutation and multiple mutations in position 53 of the heavy chain were identified that, when present individually or in combination, resulted in higher apparent affinities to gH/gL and improved CMV neutralization potency of Fab fragments expressed in bacterial cells. Three of these mutations in position 53 introduced glycosylation sites in heavy chain CDR 2 (CDR H2) that impaired binding of antibodies expressed in mammalian cells. One high affinity (KD < 10 pM) variant was identified that combined the D53N and T55R mutations while avoiding glycosylation of CDR H2. However, all the amino acid substitutions identified by phage display that improved binding affinity without introducing glycosylation sites required between two and four simultaneous nucleotide mutations to avoid glycosylation. These results indicate that the natural human antibody MSL-109 is close to a local affinity optimum. We show that affinity maturation by phage display can be used to identify and bypass barriers to in vivo affinity maturation of antibodies imposed by glycosylation and codon usage. These constraints may be relatively prevalent in human antibodies due to the codon usage and the amino acid

  8. The relation of morphology and affinity maturation in germinal centers

    CERN Document Server

    Meyer-Hermann, M

    2002-01-01

    The specific morphology of germinal centers is analyzed in the context of the optimization of the humoral immune response. The relevance of dark and light zones for the affinity maturation process is investigated in the framework of a theoretical model for the germinal center reaction. Especially, it is shown that an intermediate appearance of dark zones in germinal center reactions is advantageous for the process of antibody optimization.

  9. The Protein-Protein Interface Evolution Acts in a Similar Way to Antibody Affinity Maturation*

    OpenAIRE

    Li, Bohua; Zhao, Lei; Wang, Chong; Guo, Huaizu; Wu, Lan; Zhang, Xunming; Qian, Weizhu; Wang, Hao; Guo, Yajun

    2009-01-01

    Understanding the evolutionary mechanism that acts at the interfaces of protein-protein complexes is a fundamental issue with high interest for delineating the macromolecular complexes and networks responsible for regulation and complexity in biological systems. To investigate whether the evolution of protein-protein interface acts in a similar way as antibody affinity maturation, we incorporated evolutionary information derived from antibody affinity maturation with common simulation techniq...

  10. Affine Moment Invariants Generated by Graph Method

    Czech Academy of Sciences Publication Activity Database

    Suk, Tomáš; Flusser, Jan

    2011-01-01

    Roč. 44, č. 9 (2011), 2047 – 2056. ISSN 0031-3203 R&D Projects: GA ČR(CZ) GA102/08/1593 Institutional research plan: CEZ:AV0Z10750506 Keywords : Image moments * Object recognition * Affine transformation * Affine moment invariants * Pseudoinvariants * Graph representation * Irreducibility * Independence Subject RIV: IN - Informatics, Computer Science Impact factor: 2.292, year: 2011 http://library.utia.cas.cz/separaty/2011/ZOI/suk-0359752.pdf

  11. A mathematical model for the germinal center morphology and affinity maturation

    CERN Document Server

    Meyer-Hermann, M

    2002-01-01

    During germinal center reactions the appearance of two specific zones is observed: the dark and the light zone. Up to now, the origin and function of these zones are poorly understood. In the framework of a stochastic and discrete model several possible pathways of zone development during germinal center reactions are investigated. The importance of the zones in the germinal center for affinity maturation, i.e. the process of antibody optimization is discussed.

  12. In vitro evolution and affinity-maturation with Coliphage qβ display.

    Directory of Open Access Journals (Sweden)

    Claudia Skamel

    Full Text Available The Escherichia coli bacteriophage, Qβ (Coliphage Qβ, offers a favorable alternative to M13 for in vitro evolution of displayed peptides and proteins due to high mutagenesis rates in Qβ RNA replication that better simulate the affinity maturation processes of the immune response. We describe a benchtop in vitro evolution system using Qβ display of the VP1 G-H loop peptide of foot-and-mouth disease virus (FMDV. DNA encoding the G-H loop was fused to the A1 minor coat protein of Qβ resulting in a replication-competent hybrid phage that efficiently displayed the FMDV peptide. The surface-localized FMDV VP1 G-H loop cross-reacted with the anti-FMDV monoclonal antibody (mAb SD6 and was found to decorate the corners of the Qβ icosahedral shell by electron microscopy. Evolution of Qβ-displayed peptides, starting from fully degenerate coding sequences corresponding to the immunodominant region of VP1, allowed rapid in vitro affinity maturation to SD6 mAb. Qβ selected under evolutionary pressure revealed a non-canonical, but essential epitope for mAb SD6 recognition consisting of an Arg-Gly tandem pair. Finally, the selected hybrid phages induced polyclonal antibodies in guinea pigs with good affinity to both FMDV and hybrid Qβ-G-H loop, validating the requirement of the tandem pair epitope. Qβ-display emerges as a novel framework for rapid in vitro evolution with affinity-maturation to molecular targets.

  13. Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis.

    Science.gov (United States)

    Bishop, S A; Bailey, M; Lucke, V M; Stokes, C R

    1992-07-01

    An experimental model of proliferative glomerulonephritis (GN) in the cat, which closely resembles human proliferative forms of GN, has been used to study the role of antibody and antibody affinity in the development of immune complex-mediated renal disease. The serum IgG and IgM antibody response to antigen, average antibody affinity (avidity) and affinity heterogeneity of the IgG and IgM populations was assessed at varying times after commencement of chronic immunization with the antigen, human serum albumin (HSA), by enzyme immunoassay. Cats could be classified according to whether they were "low", "intermediate" or "high" IgG responders, by quantification of serum IgG values. Cats with the lowest serum IgG values failed to develop glomerulonephritis. However, there was no relationship between actual IgG values and the severity of the induced disease. In contrast to IgG, there was no division of cats into low or high IgM anti-HSA responders. Again, cats with the lowest IgM values failed to develop GN, but, more interestingly, a late, marked increase in serum IgM anti-HSA occurred only in cats that developed clinical signs of GN (anterior uveitis and nephrotic syndrome). Maturation of average, functional IgG affinity (avidity) for HSA following chronic immunization was clearly demonstrated for all cats. At the end of the experiment, all cats had IgG of high affinity for HSA and the average affinity heterogeneity of the IgG populations was less than in measurements taken earlier. Values of IgG affinity at the end of the experiment were very similar both in cats which developed GN and in those which remained clinically, biochemically and pathologically normal. In contrast to IgG antibody, some cats developed IgM of increased affinity, whilst others produced antibody of reduced affinity, following chronic immunization. There was no correlation between the development of disease and the production of either low or high affinity IgM antibody. Data indicated that an

  14. Selection, affinity maturation, and characterization of a human scFv antibody against CEA protein

    International Nuclear Information System (INIS)

    CEA is a tumor-associated antigen abundantly expressed on several cancer types, including those naturally refractory to chemotherapy. The selection and characterization of human anti-CEA single-chain antibody fragments (scFv) is a first step toward the construction of new anticancer monoclonal antibodies designed for optimal blood clearance and tumor penetration. The human MA39 scFv, selected for its ability to recognize a CEA epitope expressed on human colon carcinomas, was first isolated from a large semi-synthetic ETH-2 antibody phage library, panned on human purified CEA protein. Subsequently, by in vitro mutagenesis of a gene encoding for the scFv MA39, a new library was established, and new scFv antibodies with improved affinity towards the CEA cognate epitope were selected and characterized. The scFv MA39 antibody was affinity-maturated by in vitro mutagenesis and the new scFv clone, E8, was isolated, typed for CEA family member recognition and its CEACAM1, 3 and 5 shared epitope characterized for expression in a large panel of human normal and tumor tissues and cells. The binding affinity of the scFv E8 is in a range for efficient, in vivo, antigen capture in tumor cells expressing a shared epitope of the CEACAM1, 3 and 5 proteins. This new immunoreagent meets all criteria for a potential anticancer compound: it is human, hence poorly or not at all immunogenic, and it binds selectively and with good affinity to the CEA epitope expressed by metastatic melanoma and colon and lung carcinomas. Furthermore, its small molecular size should provide for efficient tissue penetration, yet give rapid plasma clearance

  15. Affine Moment Invariants Generated by Automated Solution of the Equations

    Czech Academy of Sciences Publication Activity Database

    Suk, Tomáš; Flusser, Jan

    Los Alamitos : IEEE Press, 2008, s. 3270-3273. ISBN 978-1-4244-2174-9. [19th International Conference on Pattern Recognition. Tampa (US), 07.12.2008-11.12.2008] R&D Projects: GA ČR GA102/08/1593 Institutional research plan: CEZ:AV0Z10750506 Keywords : affine moment invariants * object recognition * Cayley-Aronhold differential equation Subject RIV: JD - Computer Applications, Robotics http://library.utia.cas.cz/separaty/2008/ZOI/suk-affine moment invariants generated by automated solution of the equations. pdf

  16. Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes

    OpenAIRE

    Achenbach, Peter; Koczwara, Kerstin; Knopff, Annette; Naserke, Heike; Ziegler, Anette-G.; Bonifacio, Ezio

    2004-01-01

    Children at risk for type 1 diabetes can develop early insulin autoantibodies (IAAs). Many, but not all, of these children subsequently develop multiple islet autoantibodies and diabetes. To determine whether disease progression is reflected by autoantibody maturity, IAA affinity was measured by competitive radiobinding assay in first and subsequent IAA-positive samples from children followed from birth in the BABYDIAB cohort. IAA affinity in first positive samples ranged from less than 106 l...

  17. Engineering protein therapeutics: predictive performances of a structure-based virtual affinity maturation protocol.

    Science.gov (United States)

    Oberlin, Michael; Kroemer, Romano; Mikol, Vincent; Minoux, Hervé; Tastan, Erdogan; Baurin, Nicolas

    2012-08-27

    The implementation of a structure based virtual affinity maturation protocol and evaluation of its predictivity are presented. The in silico protocol is based on conformational sampling of the interface residues (using the Dead End Elimination/A* algorithm), followed by the estimation of the change of free energy of binding due to a point mutation, applying MM/PBSA calculations. Several implementations of the protocol have been evaluated for 173 mutations in 7 different protein complexes for which experimental data were available: the use of the Boltzamnn averaged predictor based on the free energy of binding (ΔΔG(*)) combined with the one based on its polar component only (ΔΔE(pol*)) led to the proposal of a subset of mutations out of which 45% would have successfully enhanced the binding. When focusing on those mutations that are less likely to be introduced by natural in vivo maturation methods (99 mutations with at least two base changes in the codon), the success rate is increased to 63%. In another evaluation, focusing on 56 alanine scanning mutations, the in silico protocol was able to detect 89% of the hot-spots. PMID:22788756

  18. Crystal structure of an affinity-matured prolactin complexed to its dimerized receptor reveals the topology of hormone binding site 2

    DEFF Research Database (Denmark)

    Broutin, Isabelle; Jomain, Jean-Baptiste; Tallet, Estelle; Van Agthoven, Jan; Raynal, Bertand; Hoos, Sylviane; Kragelund, Birthe Brandt; Kelly, Paul; Ducroix, Alexandre; England, Patrick; Goffin, Vincent

    2010-01-01

    We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, a closely related...... components of PRL site 2 ("three-pin plug"): the conserved glycine 129 of helix alpha3, the hydrogen bond network involving surrounding residues (glycine cavity), and the N terminus. The model provides a molecular basis for the properties of the different PRL analogs designed to date, including PRLR...

  19. Affinity maturation of anti-(4-hydroxy-3-nitrophenyl)acetyl antibodies accompanies a modulation of antigen specificity.

    Science.gov (United States)

    Oda, Masayuki; Azuma, Takachika

    2016-02-01

    Anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies bearing λ1 chains are known to possess fine specificity, referred to as heterocliticity, which causes these antibodies to bind to hapten analogues such as (4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NIP) and (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP) with higher affinity than to the autologous hapten, NP. They also show preferential binding to the phenolate form of hapten than to the phenolic form. We address here the question of whether affinity maturation accompanies in the fine specificity of these antibodies by analyzing the interaction between NP1-, NIP1-, or NNP1-hen egg lysozyme and anti-NP antibodies that possess different association constants to NP using a surface plasmon resonance biosensor. We measured interactions at various pH values and found that heterocliticity as well as preferential binding to the phenolate form of hapten were most prominent in a germline antibody having immature affinity and that fine specificity becomes less evident, i.e., anti-NP antibodies become more specific to the immunizing antigen, NP during the process of affinity maturation. PMID:26688069

  20. Millennials. The traits of a generation, the problematic maturation

    Directory of Open Access Journals (Sweden)

    Jacopo Bernardini

    2014-04-01

    Full Text Available The millennial label is being increasingly attributed to the contemporary youth in an attempt to differentiate and circumscribe a vast and multiform generational class, yet extraordinary homogeneous for several characteristics. We will look at three of those characters that mostly identify such class: the unique connection with technology, socio-political pragmatism and tendency to presentism. Characters that can be associated with unprecedented and uncertain visions of the future, work and family and, therefore, the very concept of social maturity.

  1. XGFR*, a novel affinity-matured bispecific antibody targeting IGF-1R and EGFR with combined signaling inhibition and enhanced immune activation for the treatment of pancreatic cancer.

    Science.gov (United States)

    Schanzer, Juergen M; Wartha, Katharina; Moessner, Ekkehard; Hosse, Ralf J; Moser, Samuel; Croasdale, Rebecca; Trochanowska, Halina; Shao, Cuiying; Wang, Peng; Shi, Lei; Weinzierl, Tina; Rieder, Natascha; Bacac, Marina; Ries, Carola H; Kettenberger, Hubert; Schlothauer, Tilman; Friess, Thomas; Umana, Pablo; Klein, Christian

    2016-01-01

    The epidermal growth factor receptor (EGFR) and the insulin-like growth factor-1 receptor (IGF-1R) play critical roles in tumor growth, providing a strong rationale for the combined inhibition of IGF-1R and EGFR signaling in cancer therapy. We describe the design, affinity maturation, in vitro and in vivo characterization of the bispecific anti-IGF-1R/EGFR antibody XGFR*. XGFR* is based on the bispecific IgG antibody XGFR, which enabled heterodimerization of an IGF-1R binding scFab heavy chain with an EGFR-binding light and heavy chain by the "knobs-into-holes" technology. XGFR* is optimized for monovalent binding of human EGFR and IGF-1R with increased binding affinity for IGF-1R due to affinity maturation and highly improved protein stability to oxidative and thermal stress. It bears an afucosylated Fc-portion for optimal induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Stable Chinese hamster ovary cell clones with production yields of 2-3 g/L were generated, allowing for large scale production of the bispecific antibody. XGFR* potently inhibits EGFR- and IGF-1R-dependent receptor phosphorylation, reduces tumor cell proliferation in cells with heterogeneous levels of IGF-1R and EGFR receptor expression and induces strong ADCC in vitro. A comparison of pancreatic and colorectal cancer lines demonstrated superior responsiveness to XGFR*-mediated signaling and tumor growth inhibition in pancreatic cancers that frequently show a high degree of IGF-1R/EGFR co-expression. XGFR* showed potent anti-tumoral efficacy in the orthotopic MiaPaCa-2 pancreatic xenograft model, resulting in nearly complete tumor growth inhibition with significant number of tumor remissions. In summary, the bispecific anti-IGF-1R/EGFR antibody XGFR* combines potent signaling and tumor growth inhibition with enhanced ADCC induction and represents a clinical development candidate for the treatment of pancreatic cancer. PMID:26984378

  2. Development of a fourth generation predictive capability maturity model.

    Energy Technology Data Exchange (ETDEWEB)

    Hills, Richard Guy; Witkowski, Walter R.; Urbina, Angel; Rider, William J.; Trucano, Timothy Guy

    2013-09-01

    The Predictive Capability Maturity Model (PCMM) is an expert elicitation tool designed to characterize and communicate completeness of the approaches used for computational model definition, verification, validation, and uncertainty quantification associated for an intended application. The primary application of this tool at Sandia National Laboratories (SNL) has been for physics-based computational simulations in support of nuclear weapons applications. The two main goals of a PCMM evaluation are 1) the communication of computational simulation capability, accurately and transparently, and 2) the development of input for effective planning. As a result of the increasing importance of computational simulation to SNL's mission, the PCMM has evolved through multiple generations with the goal to provide more clarity, rigor, and completeness in its application. This report describes the approach used to develop the fourth generation of the PCMM.

  3. Development of a 'mouse and human cross-reactive' affinity-matured exosite inhibitory human antibody specific to TACE (ADAM17) for cancer immunotherapy.

    Science.gov (United States)

    Kwok, Hang Fai; Botkjaer, Kenneth A; Tape, Christopher J; Huang, Yanchao; McCafferty, John; Murphy, Gillian

    2014-06-01

    We previously showed that a human anti-TACE antibody, D1(A12), is a potent inhibitor of TNF-α converting enzyme (TACE) ectodomain proteolysis and has pharmacokinetic properties suitable for studies of the inhibition of TACE-dependent growth factor shedding in relation to possible therapeutic applications. However, the lack of murine TACE immunoreactivity limits pre-clinical in vivo studies to human xenograft models which are poor analogies to in situ pathology and are not considered clinically predictive. Here, to overcome these limitations, we set out to develop a 'mouse and human cross-reactive' specific anti-TACE antibody. We first re-investigated the originally selected anti-TACE ectodomain phage-display clones, and isolated a lead 'mouse-human cross-reactive' anti-TACE scFv, clone A9. We reformatted scFv-A9 into an IgG2 framework for comprehensive biochemical and cellular characterization and further demonstrated that A9 is an exosite TACE inhibitor. However, surface plasmon resonance analysis and quenched-fluorescent (QF) peptide assay indicated that IgG reformatting of A9 caused low binding affinity and an 80-fold reduction in TACE ectodomain inhibition, severely limiting its efficacy. To address this, we constructed second generation phage-display randomization libraries focused on the complementarity-determining region 3, and carried out affinity selections shuffling between human and mouse TACE ectodomain as antigen in addition to an off-rate selection to increase the chance of affinity improvement. The bespoke 'three-step' selections enabled a 100-fold affinity enhancement of A9 IgG, and also improved its IC50 in a QF peptide assay to 0.2 nM. In human and mouse cancer cell assays, matured A9 IgG showed significant cell-surface TACE inhibition as a monotherapy or combination therapy with chemotherapeutic agent. Collectively, these data suggest that we successfully developed an exosite inhibitor of TACE with sub-nanomolar affinity, which possesses both

  4. Pairing Problem of Generators in Non-twisted Affine Lie Algebras

    Institute of Scientific and Technical Information of China (English)

    XU Hai-xia; LU Cai-hui

    2001-01-01

    In this paper, we discuss the pairing problem of generators in four affine Lie algebra. That is,for any given imaginary root vector x ∈ g (A), there exists y such that x and y generate a subalgebra containing g' (A).

  5. Affinity maturation of anti-TNF-alpha scFv with somatic hypermutation in non-B cells.

    Science.gov (United States)

    Chen, Shaopeng; Qiu, Junkang; Chen, Chuan; Liu, Chunchun; Liu, Yuheng; An, Lili; Jia, Junying; Tang, Jie; Wu, Lijun; Hang, Haiying

    2012-06-01

    Activation-induced cytidine deaminase (AID) is required for the generation of antibody diversity through initiating both somatic hypermutation (SHM) and class switch recombination. A few research groups have successfully used the feature of AID for generating mutant libraries in directed evolution of target proteins in B cells in vitro. B cells, cultured in suspension, are not convenient for transfection and cloning. In this study, we established an AID-based mutant accumulation and sorting system in adherent human cells. Mouse AID gene was first transfected into the human non-small cell lung carcinoma H1299 cells, and a stable cell clone (H1299-AID) was selected. Afterwards, anti-hTNF-α scFv (ATscFv) was transfected into H1299-AID cells and ATscFv was displayed on the surface of H1299-AID cells. By 4-round amplification/flow cytometric sorting for cells with the highest affinities to hTNF-alpha, two ATscFv mutant gene clones were isolated. Compared with the wild type ATscFv, the two mutants were much more efficient in neutralizing cytotoxicity of hTNF-alpha. The results indicate that directed evolution by somatic hypermutation can be carried out in adherent non-B cells, which makes directed evolution in mammalian cells easier and more efficient. PMID:22467272

  6. Model of Earthquake Generation Exhibiting Self-Organized Criticality with Self-Affine Fault Surfaces

    International Nuclear Information System (INIS)

    Generation of earthquakes has not been still understood. However, some statistical properties of seismicity are established such as magnitude-frequency distribution indicating power law. In this study, we numerically investigate one-dimensional spring-block earthquake model, considering self-affine fault surfaces, in order to understand such statistical properties

  7. Combining somatic mutations present in different in vivo affinity-matured antibodies isolated from immunized Lama glama yields ultra-potent antibody therapeutics.

    Science.gov (United States)

    Klarenbeek, Alex; Blanchetot, Christophe; Schragel, Georg; Sadi, Ava S; Ongenae, Nico; Hemrika, Wieger; Wijdenes, John; Spinelli, Silvia; Desmyter, Aline; Cambillau, Christian; Hultberg, Anna; Kretz-Rommel, Anke; Dreier, Torsten; De Haard, Hans J W; Roovers, Rob C

    2016-04-01

    Highly potent human antibodies are required to therapeutically neutralize cytokines such as interleukin-6 (IL-6) that is involved in many inflammatory diseases and malignancies. Although a number of mutagenesis approaches exist to perform antibody affinity maturation, these may cause antibody instability and production issues. Thus, a robust and easy antibody affinity maturation strategy to increase antibody potency remains highly desirable. By immunizing llama, cloning the 'immune' antibody repertoire and using phage display, we selected a diverse set of IL-6 antagonistic Fabs. Heavy chain shuffling was performed on the Fab with lowest off-rate, resulting in a panel of variants with even lower off-rate. Structural analysis of the Fab:IL-6 complex suggests that the increased affinity was partly due to a serine to tyrosine switch in HCDR2. This translated into neutralizing capacity in an in vivo model of IL-6 induced SAA production. Finally, a novel Fab library was designed, encoding all variations found in the natural repertoire of VH genes identified after heavy chain shuffling. High stringency selections resulted in identification of a Fab with 250-fold increased potency when re-formatted into IgG1. Compared with a heavily engineered anti-IL-6 monoclonal antibody currently in clinical development, this IgG was at least equally potent, showing the engineering process to have had led to a highly potent anti-IL-6 antibody. PMID:26945588

  8. Generational affinities and discourses of difference: a case study of highly skilled information technology workers.

    Science.gov (United States)

    McMullin, Julie Ann; Duerden Comeau, Tammy; Jovic, Emily

    2007-06-01

    Sociologists theorizing the concept of 'generation' have traditionally looked to birth cohorts sharing major social upheavals such as war or decolonization to explain issues of generational solidarity and identity affiliation. More recently, theorists have drawn attention to the cultural elements where generations are thought to be formed through affinities with music or other types of popular culture during the 'coming of age' stage of life. In this paper, we ask whether developments in computer technology, which have both productive and cultural components, provide a basis for generational formation and identity and whether generational discourse is invoked to create cultures of difference in the workplace. Qualitative data from a sample of Information Technology workers show that these professionals mobilize 'generational' discourse and draw upon notions of 'generational affinity' with computing technology (e.g. the fact that people of different ages were immersed to varying degrees in different computing technologies) in explaining the youthful profile of IT workers and employees' differing levels of technological expertise. PMID:17610624

  9. Devices and approaches for generating specific high-affinity nucleic acid aptamers

    Science.gov (United States)

    Szeto, Kylan; Craighead, Harold G.

    2014-09-01

    High-affinity and highly specific antibody proteins have played a critical role in biological imaging, medical diagnostics, and therapeutics. Recently, a new class of molecules called aptamers has emerged as an alternative to antibodies. Aptamers are short nucleic acid molecules that can be generated and synthesized in vitro to bind to virtually any target in a wide range of environments. They are, in principal, less expensive and more reproducible than antibodies, and their versatility creates possibilities for new technologies. Aptamers are generated using libraries of nucleic acid molecules with random sequences that are subjected to affinity selections for binding to specific target molecules. This is commonly done through a process called Systematic Evolution of Ligands by EXponential enrichment, in which target-bound nucleic acids are isolated from the pool, amplified to high copy numbers, and then reselected against the desired target. This iterative process is continued until the highest affinity nucleic acid sequences dominate the enriched pool. Traditional selections require a dozen or more laborious cycles to isolate strongly binding aptamers, which can take months to complete and consume large quantities of reagents. However, new devices and insights from engineering and the physical sciences have contributed to a reduction in the time and effort needed to generate aptamers. As the demand for these new molecules increases, more efficient and sensitive selection technologies will be needed. These new technologies will need to use smaller samples, exploit a wider range of chemistries and techniques for manipulating binding, and integrate and automate the selection steps. Here, we review new methods and technologies that are being developed towards this goal, and we discuss their roles in accelerating the availability of novel aptamers.

  10. Multifrequency eddy current testing of steam generator tubes using optimal affine transformation

    International Nuclear Information System (INIS)

    An alternative technique was developed for the implementation of multifrequency/multiparameter concepts for extracting defect signal information from complex measured eddy current data. The approach uses affine transformations which appropriately shape and rotate the basic frequency response similar to procedures used in image registration. Vector subtraction of the auxiliary frequency signals is then performed to obtain the relevant eddy current defect signal. The mathematics of the technique are discussed. The experimental setup for reactor steam generator tube imaging is described and results are graphed

  11. High Affinity, Developability and Functional Size: The Holy Grail of Combinatorial Antibody Library Generation

    Directory of Open Access Journals (Sweden)

    Kathrin Tissot

    2011-05-01

    Full Text Available Since the initial description of phage display technology for the generation of human antibodies, a variety of selection methods has been developed. The most critical parameter for all in vitro-based approaches is the quality of the antibody library. Concurrent evolution of the libraries has allowed display and selection technologies to reveal their full potential. They come in different flavors, from naïve to fully synthetic and differ in terms of size, quality, method of preparation, framework and CDR composition. Early on, the focus has mainly been on affinities and thus on library size and diversity. Subsequently, the increased awareness of developability and cost of goods as important success factors has spurred efforts to generate libraries with improved biophysical properties and favorable production characteristics. More recently a major focus on reduction of unwanted side effects through reduced immunogenicity and improved overall biophysical behavior has led to a re-evaluation of library design.

  12. Reconstruction of burial history, temperature, source rock maturity and hydrocarbon generation in the northwestern Dutch offshore

    NARCIS (Netherlands)

    Abdul Fattah, R.; Verweij, J.M.; Witmans, N.; Veen, J.H. ten

    2012-01-01

    3D basin modelling is used to investigate the history of maturation and hydrocarbon generation on the main platforms in the northwestern part of the offshore area of the Netherlands. The study area covers the Cleaverbank and Elbow Spit Platforms. Recently compiled maps and data are used to build the

  13. Development of a new protocol for 2-day generation of mature dendritic cells from human monocytes

    Directory of Open Access Journals (Sweden)

    Obermaier Bianca

    2003-01-01

    Full Text Available We developed a new 2-day protocol for the generation of dendritic cells (DCs from human monocytes in vitro. First, we demonstrated that 24 hours of culture with GM-CSF and IL-4 are sufficient to generate immature DCs capable of antigen uptake. We then compared two different strategies for DC maturation: proinflammatory mediators were either added together with GM-CSF and IL-4 from the beginning of cell culture or added after 24 hours of differentiation with GM-CSF and IL-4. After 48 hours of total culture period, expression of activation markers was more pronounced in cells generated by the 2-step differentiation and activation method. Our new protocol for 2-day DC differentiation reduces labor, cost and time and also reliably renders high numbers of mature and viable DCs.

  14. The Lectin Frontier Database (LfDB, and Data Generation Based on Frontal Affinity Chromatography

    Directory of Open Access Journals (Sweden)

    Jun Hirabayashi

    2015-01-01

    Full Text Available Lectins are a large group of carbohydrate-binding proteins, having been shown to comprise at least 48 protein scaffolds or protein family entries. They occur ubiquitously in living organisms—from humans to microorganisms, including viruses—and while their functions are yet to be fully elucidated, their main underlying actions are thought to mediate cell-cell and cell-glycoconjugate interactions, which play important roles in an extensive range of biological processes. The basic feature of each lectin’s function resides in its specific sugar-binding properties. In this regard, it is beneficial for researchers to have access to fundamental information about the detailed oligosaccharide specificities of diverse lectins. In this review, the authors describe a publicly available lectin database named “Lectin frontier DataBase (LfDB”, which undertakes the continuous publication and updating of comprehensive data for lectin-standard oligosaccharide interactions in terms of dissociation constants (Kd’s. For Kd determination, an advanced system of frontal affinity chromatography (FAC is used, with which quantitative datasets of interactions between immobilized lectins and >100 fluorescently labeled standard glycans have been generated. The FAC system is unique in its clear principle, simple procedure and high sensitivity, with an increasing number (>67 of associated publications that attest to its reliability. Thus, LfDB, is expected to play an essential role in lectin research, not only in basic but also in applied fields of glycoscience.

  15. K-AP: Generating specified K clusters by efficient Affinity Propagation

    KAUST Repository

    Zhang, Xiangliang

    2010-12-01

    The Affinity Propagation (AP) clustering algorithm proposed by Frey and Dueck (2007) provides an understandable, nearly optimal summary of a data set. However, it suffers two major shortcomings: i) the number of clusters is vague with the user-defined parameter called self-confidence, and ii) the quadratic computational complexity. When aiming at a given number of clusters due to prior knowledge, AP has to be launched many times until an appropriate setting of self-confidence is found. The re-launched AP increases the computational cost by one order of magnitude. In this paper, we propose an algorithm, called K-AP, to exploit the immediate results of K clusters by introducing a constraint in the process of message passing. Through theoretical analysis and experimental validation, K-AP was shown to be able to directly generate K clusters as user defined, with a negligible increase of computational cost compared to AP. In the meanwhile, K-AP preserves the clustering quality as AP in terms of the distortion. K-AP is more effective than k-medoids w.r.t. the distortion minimization and higher clustering purity. © 2010 IEEE.

  16. Affinity isolation of antigen-specific circulating B cells for generation of phage display-derived human monoclonal antibodies

    DEFF Research Database (Denmark)

    Ditzel, Henrik

    2009-01-01

    A method is described for affinity isolation of antigen-specific circulating B cells of interest for subsequent generation of immune antibody phage display libraries. This approach should overcome the problem of low yields of monoclonal antibodies of interest in the libraries generated from...... the frequency of antibody phage particles of interest in the library and allow for efficient isolation monoclonal antibodies with the predefined specificity....

  17. In vivo generation of a mature and functional artificial skeletal muscle.

    Science.gov (United States)

    Fuoco, Claudia; Rizzi, Roberto; Biondo, Antonella; Longa, Emanuela; Mascaro, Anna; Shapira-Schweitzer, Keren; Kossovar, Olga; Benedetti, Sara; Salvatori, Maria L; Santoleri, Sabrina; Testa, Stefano; Bernardini, Sergio; Bottinelli, Roberto; Bearzi, Claudia; Cannata, Stefano M; Seliktar, Dror; Cossu, Giulio; Gargioli, Cesare

    2015-04-01

    Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting. PMID:25715804

  18. Particle Display: A Quantitative Screening Method for Generating High-Affinity Aptamers**

    OpenAIRE

    Wang, J.; Gong, Q; N Maheshwari; Eisenstein, M; Arcila, ML; Kosik, KS; Soh, HT

    2014-01-01

    We report an aptamer discovery technology that reproducibly yields higher affinity aptamers in fewer rounds compared to conventional selection. Our method (termed particle display) transforms libraries of solution-phase aptamers into "aptamer particles", each displaying many copies of a single sequence on its surface. We then use fluorescence-activated cell sorting (FACS) to individually measure the relative affinities of >108 aptamer particles and sort them in a high-throughput manner. Throu...

  19. Thermal maturity, alginite-bitumen transformation, and hydrocarbon generation in Upper Ordovician source rocks, Saskatchewan, Canada

    Energy Technology Data Exchange (ETDEWEB)

    Stasiuk, L.D.; Osadetz, K.G. (Inst. of Sedimentary and Petroleum Geology, Calgary, Alberta (Canada))

    Organic petrological techniques have been used to study the alginite-bitumen-oil transformation in Upper Ordovician Yeoman Formation kukersite source rocks of the northern Williston Basin, Saskatchewan, Canada. The kukersites are characterized by two distinct interlaminated microfacies, disseminated and stromatolitic, each representing a growth stage of the precursor to the alginite maceral Gloeocapsomorpha prisca. Different rates of thermal maturation and thresholds of petroleum generation for the two G. prisca maceral subvarieties are indicated by different rates of percent reflectance in oil increase and are verified by shifts in fluorescence spectra and observations on transformation into bitumen. With increasing thermal maturation, disseminated G.prisca reaches a softening stage, losing its primary morphological features as it is transformed from a primary to a secondary maceral (bitumen). The stromatolitic subvariety of G. prisca does not display comparable alteration in response to increasing thermal stress. Hot stage experiments conducted on doubly polished thin sections of the kukersites support the optical discrepancies observed between the two maceral subvarieties in the subsurface. These findings indicate that hydrocarbon generation from kukersites may involve two steps controlled largely by organic microfacies. Inception of petroleum generation appears to occur at a depth of 3000 m for the disseminated alginite. Bitumen has been cracked to anisotropic 'coke' on a local thermal anomaly, and peak to postgeneration of petroleum has occurred at a maximum temperature of 148[degree]C, as suggested by homogenization temperatures for fluid inclusions.

  20. Investigation of complexes with bone affinity using the In vivo generator system 166 Dy/166 Ho

    International Nuclear Information System (INIS)

    The importance of this original research lies in the fact that it has proven that the [166Dy]Dy/166Ho-EDTMP in vivo generator system is a stable complex that can be used as a therapeutic radiopharmaceutical. Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. Bone-seeking radiopharmaceuticals such as 166Ho-DOTMP or 153Sm-DTMP, have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other hematological malignancies or have shown excellent results in palliative bone metastasis pain therapy, respectively. As lanthanides have similar chemical characteristics the phosphonate with bone affinity (EDTMP) labeled with Dy/Ho can be used for marrow ablation while causing minimal irradiation to normal organs. This in vivo generator system has not been previously reported. The aim of this research was to label EDTMP (ethylene diamine tetramethylene phosphonate) with 166Dy/166Ho; to evaluate the in vitro and in vivo stability of both 166Dy-EDTMP and 166Ho-EDTMP complexes when the daughter 166Ho is formed as a dysprosium decay product; to determine the bone marrow cytotoxic and genotoxic effect in mice and to evaluate, by histopathology, the myeloablative potential of the [166Dy]Dy/166Ho-EDTMP in vivo generator system. 166Dy was obtained by neutron irradiation of enriched 164Dy2O3 in a TRIGA Mark III reactor. Labeling was carried out in an aqueous phosphate medium at pH 8.0 by addition of 166DyCl3 to EDTMP at a molar ratio 1:1.75, with >99 % radiochemical purity, as determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). In vitro studies demonstrated that 166Dy/166Ho-EDTMP is unstable after dilution in saline but stable in human serum with no translocation of the daughter nucleus subsequent to β decay of 166Dy, which could release free 166Ho3+. Biodistribution in mice, after I.V. administration

  1. Generation of high-affinity DNA aptamers using an expanded genetic alphabet.

    Science.gov (United States)

    Kimoto, Michiko; Yamashige, Rie; Matsunaga, Ken-ichiro; Yokoyama, Shigeyuki; Hirao, Ichiro

    2013-05-01

    DNA aptamers produced with natural or modified natural nucleotides often lack the desired binding affinity and specificity to target proteins. Here we describe a method for selecting DNA aptamers containing the four natural nucleotides and an unnatural nucleotide with the hydrophobic base 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). We incorporated up to three Ds nucleotides in a random sequence library, which is expected to increase the chemical and structural diversity of the DNA molecules. Selection experiments against two human target proteins, vascular endothelial cell growth factor-165 (VEGF-165) and interferon-γ (IFN-γ), yielded DNA aptamers that bind with KD values of 0.65 pM and 0.038 nM, respectively, affinities that are >100-fold improved over those of aptamers containing only natural bases. These results show that incorporation of unnatural bases can yield aptamers with greatly augmented affinities, suggesting the potential of genetic alphabet expansion as a powerful tool for creating highly functional nucleic acids. PMID:23563318

  2. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  3. Effects of source and thermal maturity on the distribution of aromatics and biomarkers in artificially generated oils

    Science.gov (United States)

    Chang, Ying-Ju

    2010-05-01

    Ying-Ju Chang (1), Wuu-Liang Huang (2), Suh-Huey Wu (3), Cheng-Lung Kuo (3) (1) Department of Geosciences, National Taiwan University, Taipei, Taiwan (r93224103@ntu.edu.tw); (2) Department of Geosciences, National Taiwan University, Taipei, Taiwan; (3) Exploration and Development Research Institute, Chinese Petroleum Corp., Taiwan Oils generated from isolated kerogens from a variety of source rocks, including two marine shales, two terrestrial coals, and three lacustrine oil shales were characterized for the effects of source and maturity on the distributions of hydrocarbons compounds. Experiments were conducted by confined pressure (gold-tube) pyrolysis at 320 deg. Celsius at four laboratory maturities (0.79, 0.95, 1.10, 1.34 Easy%Ro). The results show that normal alkane distribution in oils from different kerogens exhibit distinct preference in carbon number and predominance in specific compounds. The carbon preference index (CPI) and odd-even predominance (OEP) ratios tend to approach to 1 with increasing maturity. Oils from two terrestrial kerogens show higher Pr/n-C17 ratio than lacustrine kerogens (Green-river oil shale, GR) and vice versa for Ph/n-C18 ratio. Both ratios decrease with increasing maturity but show distinct trends for different kerogens. The (Pr/n-C17) and (Ph/n-C18) ratios for the lamosite, torbanite, and two marine kerogens are very low at all studied maturities. The pristane/phytane (Pr/Ph) and [(Pr/C17)/(Ph/C18)] ratios in oils from three major kerogen types vary barely with maturity but are discernible in diverse organic types, implying good source indication. The methylphenanthrene ratios (MPR) for most kerogens, which vary significantly only at maturities higher than 1.0 %Ro, are suitable for high maturity indication. The methylphenanthrene distribution fraction (MPDF), in general, increases slightly with increasing maturity, except in torbanite. The MPDF parameter for GR kerogen exhibits best linear correlation with maturity whereas

  4. SOX2+ Cell Population from Normal Human Brain White Matter Is Able to Generate Mature Oligodendrocytes

    Science.gov (United States)

    Oliver-De La Cruz, Jorge; Carrión-Navarro, Josefa; García-Romero, Noemí; Gutiérrez-Martín, Antonio; Lázaro-Ibáñez, Elisa; Escobedo-Lucea, Carmen; Perona, Rosario; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2014-01-01

    Objectives A number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established. Methods We used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo. Results We have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+). Conclusion Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures. PMID:24901457

  5. Cenozoic alkaline volcanic rocks with carbonatite affinity in the Bohemian Massif: Their sources and magma generation

    Czech Academy of Sciences Publication Activity Database

    Ulrych, Jaromír; Štěpánková-Svobodová, Jana

    2014-01-01

    Roč. 46, 1/2 (2014), s. 45-58. ISSN 0369-2086 R&D Projects: GA AV ČR(CZ) IAA300130902 Institutional support: RVO:67985831 Keywords : alkaline volcanic rocks * melilitic rocks * carbonatite s * magma generation * metasomatism * Cenozoic * Bohemian Massif Subject RIV: DB - Geology ; Mineralogy

  6. Generation and maturation of a vortex ring in non-Newtonian fluids

    OpenAIRE

    Bentata, Omar; Brancher, Pierre; Anne-Archard, Dominique

    2012-01-01

    Vortex rings are coherent structures that dominate the dynamics of many flows. They are present in a wide range of situations : in industrial mixing systems (in the vicinity of the agitation moving blades), but also in nature during the ejection of volcanic gas or in the wakes behind insects, birds and fishes, where a periodic release of vortex rings is observed. In this work we study the formation and maturation of a vortex ring in non-Newtonian fluids, with a special focus on shear-thinning...

  7. Assessment of the Technical Maturity of Generation IV Concepts for Test or Demonstration Reactor Applications, Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    Gougar, Hans David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-10-01

    The United States Department of Energy (DOE) commissioned a study the suitability of different advanced reactor concepts to support materials irradiations (i.e. a test reactor) or to demonstrate an advanced power plant/fuel cycle concept (demonstration reactor). As part of the study, an assessment of the technical maturity of the individual concepts was undertaken to see which, if any, can support near-term deployment. A Working Group composed of the authors of this document performed the maturity assessment using the Technical Readiness Levels as defined in DOE’s Technology Readiness Guide . One representative design was selected for assessment from of each of the six Generation-IV reactor types: gas-cooled fast reactor (GFR), lead-cooled fast reactor (LFR), molten salt reactor (MSR), supercritical water-cooled reactor (SCWR), sodium-cooled fast reactor (SFR), and very high temperature reactor (VHTR). Background information was obtained from previous detailed evaluations such as the Generation-IV Roadmap but other technical references were also used including consultations with concept proponents and subject matter experts. Outside of Generation IV activity in which the US is a party, non-U.S. experience or data sources were generally not factored into the evaluations as one cannot assume that this data is easily available or of sufficient quality to be used for licensing a US facility. The Working Group established the scope of the assessment (which systems and subsystems needed to be considered), adapted a specific technology readiness scale, and scored each system through discussions designed to achieve internal consistency across concepts. In general, the Working Group sought to determine which of the reactor options have sufficient maturity to serve either the test or demonstration reactor missions.

  8. A novel rabbit immunospot array assay on a chip allows for the rapid generation of rabbit monoclonal antibodies with high affinity.

    Directory of Open Access Journals (Sweden)

    Tatsuhiko Ozawa

    Full Text Available Antigen-specific rabbit monoclonal antibodies (RaMoAbs are useful due to their high specificity and high affinity, and the establishment of a comprehensive and rapid RaMoAb generation system has been highly anticipated. Here, we present a novel system using immunospot array assay on a chip (ISAAC technology in which we detect and retrieve antigen-specific antibody-secreting cells from the peripheral blood lymphocytes of antigen-immunized rabbits and produce antigen-specific RaMoAbs with 10(-12 M affinity within a time period of only 7 days. We have used this system to efficiently generate RaMoAbs that are specific to a phosphorylated signal-transducing molecule. Our system provides a new method for the comprehensive and rapid production of RaMoAbs, which may contribute to laboratory research and clinical applications.

  9. Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells

    Science.gov (United States)

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-01

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  10. In vivo generation of a mature and functional artificial skeletal muscle

    OpenAIRE

    Fuoco, Claudia; Rizzi, Roberto; Biondo, Antonella; Longa, Emanuela; Mascaro, Anna; Shapira-Schweitzer, Keren; Kossovar, Olga; Benedetti, Sara; Salvatori, Maria L; Santoleri, Sabrina; Testa, Stefano; Bernardini, Sergio; Bottinelli, Roberto; Bearzi, Claudia; Cannata, Stefano M.

    2015-01-01

    Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in ...

  11. PLAP efficiently generates mature antigenic peptides in vitro but in patterns distinct from ERAP11

    OpenAIRE

    Georgiadou, Dimitra; Hearn, Arron; Evnouchidou, Irini; Chroni, Angeliki; Leondiadis, Leondios; Ian A York; Rock, Kenneth L.; Stratikos, Efstratios

    2010-01-01

    All three members of the oxytocinase sub-family of M1 aminopeptidases, ERAP1 (ERAAP), ERAP2 and PLAP (IRAP), have been implicated in the generation of MHC class I-presented peptides. ERAP1 and 2 trim peptides in the endoplasmic reticulum for direct presentation whereas PLAP has been recently implicated in cross presentation. The best characterized member of the family, ERAP1, has unique enzymatic properties that fit well with its role in antigen processing. ERAP1 can trim a large variety of l...

  12. Tau-functions generating the conservation laws for generalized integrable hierarchies of KdV and affine toda type

    International Nuclear Information System (INIS)

    For a class of generalized integrable hierarchies associated with affine (twisted or untwisted) Kac-Moody algebras, an explicit representation of their local conserved densities by means of a single scalar tau-function is deduced. This tau-function acts as a partition function for the conserved densities, which fits its potential interpretation as the effective action of some quantum system. The class consists of multi-component generalizations of the Drinfel'd-Sokolov and the two-dimensional affine Toda lattice hierarchies. The relationship between the former and the approach of Feigin, Frenkel and Enriquez to soliton equations of KdV and mKdV type is also discussed. These results considerably simplify the calculation of the conserved charges carried by the soliton solutions to the equations of the hierarchy, which is important to establish their interpretation as particles. By way of illustration, we calculate the charges carried by a set of constrained KP solitons recently constructed

  13. A simple enzyme-substrate localized conjugation method to generate immobilized, functional glutathione S-transferase fusion protein columns for affinity enrichment.

    Science.gov (United States)

    Coughlin, John; Masci, Allyson; Gronke, Robert S; Bergelson, Svetlana; Co, Carl

    2016-07-15

    Immobilized protein receptors and enzymes are tools for isolating or enriching ligands and substrates based on affinity. For example, glutathione S-transferase (GST) is fused to proteins as a tag for binding to its substrate glutathione (GSH) linked to solid supports. One issue with this approach is that high-affinity interactions between receptors and ligands require harsh elution conditions such as low pH, which can result in leached receptor. Another issue is the inherent nonspecific chemical conjugation of reactive groups such as N-hydroxysuccinimide (NHS) that couple lysines to solid supports; the nonspecificity of NHS may result in residue modifications near the binding site(s) of the receptor that can affect ligand specificity. In this study, a simple conjugation procedure is presented that overcomes these limitations and results in immobilized GST fusion proteins that are functional and specific. Here, the affinity of GST for GSH was used to generate an enzyme-substrate site-specific cross-linking reaction; GSH-Sepharose was preactivated with 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) and then incubated Fc gamma receptor IIIa (FcγRIIIa)-GST. The immobilized FcγRIIIa-GST more specifically bound glycosylated immunoglobulin G1s (IgG1s) and was used to enrich nonfucosylated IgG1s from weaker binding species. This technique can be used when modifications of amino acids lead to changes in activity. PMID:27063248

  14. T Cells That Promote B-Cell Maturation in Systemic Autoimmunity

    OpenAIRE

    Weinstein, Jason S.; Hernandez, Sairy G.; Craft, Joe

    2012-01-01

    Follicular helper T (Tfh) cells play an essential role in helping B cells generate antibodies upon pathogen encounters. Such T-cell help classically occurs in germinal centers (GCs) located in B-cell follicles of secondary lymphoid organs, a site of immunoglobulin affinity maturation and isotype switching. B-cell maturation also occurs extrafollicularly, in the red pulp of the spleen and medullary cords in lymph nodes, with plasma cell formation and antibody production. Development of extrafo...

  15. Providing affinity

    DEFF Research Database (Denmark)

    Guglielmi, Michel; Johannesen, Hl

    , Essex, Hertfordshire, Norfolk and Suffolk. Research found that there was a lack of identity or sense of belonging and nothing anchoring people to the region as a whole. Common affinity is somehow forced to the people of East England and thereby we came to the conclusion that a single landmark or a...... a sense of belonging to people sharing deterritorialized synchronic experiences. But at the same time, the immersion experience is highly low tech and desperately analog, mainly based on fabulation, cartoons, and mushrooms growing in local forests. It ultimately appeals to the experienced sense of...

  16. Long-term follow-up on affinity maturation and memory B-cell generation in patients with common variable immunodeficiency

    DEFF Research Database (Denmark)

    Ballegaard, Vibe Cecilie Diederich; Permin, H; Katzenstein, T L;

    2013-01-01

    Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary immunodeficiency disorders. Immunophenotyping of memory B cells at the time of diagnosis is increasingly used for the classification of patients into subgroups with different clinical prognoses. The EUROclass...

  17. Korean Mature Women Students' Various Subjectivities in Relation to Their Motivation for Higher Education: Generational Differences amongst Women

    Science.gov (United States)

    Lee, Sunghoe

    2014-01-01

    This qualitative case study attempts to conceptualize certain "patterns" and "processes" of which 28 mature women undergraduates give meanings to their motivation for higher education in their life contexts. Particular attention has been paid to include diverse groups of women according to their age, prior educational…

  18. The N-Terminal T-T Motif of a Third-Generation HIV-1 Fusion Inhibitor Is Not Required for Binding Affinity and Antiviral Activity.

    Science.gov (United States)

    Chong, Huihui; Qiu, Zonglin; Su, Yang; He, Yuxian

    2015-08-27

    The highlighted next-generation HIV-1 fusion inhibitor peptide 1 is capped by two threonines. Here, we generated peptide 2 by deleting the T-T motif and compared their structural and antiviral properties. Significantly, two peptides showed similar helical and oligomeric states in solution, comparable binding affinities to the target, and no significant difference to inhibit HIV-1 fusion and infection. Also, the T-T motif was not associated with peptide 1 resistant mutations and its deletion did not affect peptide 1 against enfuvirtide-resistant HIV-1 mutants. The redundancy of the T-T motif was further verified by the model peptide C34 and short peptide inhibitors that mainly target the gp41 pocket, suggesting that the N-terminal T-T motif of peptide 1 could be removed or modified toward the development of new anti-HIV-1 drugs. Consistently, our data have verified that the M-T hook structure rather than the T-T motif is an efficient strategy for short peptide fusion inhibitors. PMID:26256053

  19. In- and outdoor reproduction of first generation common sole Solea solea under a natural photothermal regime: Temporal progression of sexual maturation assessed by monitoring plasma steroids and gonadotropin mRNA experssion

    NARCIS (Netherlands)

    Palstra, A.P.; Blok, M.C.; Kals, J.; Blom, E.; Tuinhof-Koelma, N.; Dirks, R.P.; Forlenza, M.; Blonk, R.J.W.

    2015-01-01

    Reproduction of many temperate fishes is seasonal and maturation and spawning of gametes are under photothermal control. Reproductive success of first generation (G1) common sole Solea solea in captivity has been low. In this study, the sexual maturation status has been assessed during the prespawni

  20. Oral priming with replicating adenovirus serotype 4 followed by subunit H5N1 vaccine boost promotes antibody affinity maturation and expands H5N1 cross-clade neutralization.

    Science.gov (United States)

    Khurana, Surender; Coyle, Elizabeth M; Manischewitz, Jody; King, Lisa R; Ishioka, Glenn; Alexander, Jeff; Smith, Jon; Gurwith, Marc; Golding, Hana

    2015-01-01

    A Phase I trial conducted in 2009-2010 demonstrated that oral vaccination with a replication competent Ad4-H5 (A/Vietnam) vector with dosages ranging from 107-1011 viral particles was well tolerated. HA-specific T-cell responses were efficiently induced, but very limited hemagglutination-inhibiting (HI) humoral responses were measured. However, a single boost of Ad4-H5-Vtn vaccinated individuals with a unadjuvanted licensed H5N1 (A/Vietnam) subunit vaccine resulted in superior HI titers compared with unprimed subjects. In the current study, the impact of Ad4-H5 priming on the quality of the polyclonal humoral immune response was evaluated using a real-time kinetics assay by surface plasmon resonance (SPR). Total binding of serum polyclonal antibodies from the Ad4-H5-Vtn primed groups against both homologous H5N1-A/Vietnam/1194/2004 (clade 1) and heterologous A/Indonesia-5/2005 (clade 2.1) HA1 head domain was significantly higher compared with sera from individuals that received subunit H5N1 vaccination alone. SPR measurements also demonstrated that the antigen-antibody complex dissociation rates (a surrogate for antibody affinity) of serum antibodies against the HA1 of H5N1-A/Vietnam were significantly higher in the Ad4-H5 primed groups compared with those from the unprimed group. Furthermore, strong correlations were observed between the antibody affinities for HA1 (but not HA2) and the virus neutralization titers against the homologous strain and a panel of heterologous clade 2 H5N1 strains. These findings support the concept of oral prime-boost vaccine approaches against pandemic influenza to elicit long-term memory B cells with high affinity capable of rapid response to variant pandemic viruses likely to emerge and adapt to human transmissions. PMID:25629161

  1. The first dose of a Haemophilus influenzae type b conjugate vaccine reactivates memory B cells: evidence for extensive clonal selection, intraclonal affinity maturation, and multiple isotype switches to IgA2

    DEFF Research Database (Denmark)

    Hougs, L; Juul, L; Ditzel, H J;

    1999-01-01

    mutations were shared by this clonal progeny, indicating that extreme clonal selection had occurred early in the clonal development. Taking into account the frequency of somatic mutations and the clone size, it was evident that the responding cell population must have originated from a mutated, highly...... that the clonal selection had been driven by affinity. Pre-existing memory cells in unvaccinated adults may explain several features of Ab responses to polysaccharide vaccines and may play a role in acquiring the ability to respond to pure polysaccharides during infancy....

  2. Crystal Structure of a Human Autoimmune Complex between IgM Rheumatoid Factor RF61 and IgG1 Fc Reveals a Novel Epitope and Evidence for Affinity Maturation

    OpenAIRE

    Duquerroy, Stephane; Stura, Enrico A; Bressanelli, Stéphane; Fabiane, Stella M.; Vaney, Marie C.; Beale, Dennis; Hamon, Maureen; Casali, Paolo; Rey, Felix A.; Sutton, Brian J.; Michael J. Taussig

    2007-01-01

    Rheumatoid factors (RF) are autoantibodies that recognize epitopes in the Fc region of immunoglobulin (Ig) G and that correlate with the clinical severity of rheumatoid arthritis (RA). Here we report the X-ray crystal-lographic structure, at 3 Å resolution, of a complex between the Fc region of human IgG1 and the Fab fragment of a monoclonal IgM RF (RF61), derived from an RA patient and with a relatively high affinity for IgG Fc. In the complex, two Fab fragments bind to each Fc at epitopes c...

  3. A discussion on the upper limit of maturity for gas generation by marine kerogens and the utmost of gas generative potential: Taking the study on the Tarim Basin as an example

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The experimental data yielded by Rock-Eval pyrolysis, kerogen atomic H/C, Py-GC and gold-tube sealing thermal simulation on the marine Cambrian-Ordovician source rock from the Tarim Basin revealed that the upper limit of maturity for natural gas generation or the "deadline of gas generation" for marine types Ⅰ and Ⅱ kerogens is equal to 3.0% of vitrinite reflectance (Ro); while the "deadline of gas generation" for type Ⅲ kerogens typically like coals is as high as 10% Ro. Thus, different organic matter has obviously different utmost maturities for gas generation. The mass-balance calculation by kerogen elements showed that when Ro>1.5%, the utmost amount of gas generation for the marine type Ⅱ kerogen is less than 185 m3/t TOC, accounting for less than 30% of its total hydrocarbon generative potential; when Ro>2.0%, it becomes 110 m3/t TOC, less than 20% of the total hydrocarbon generative potential. The amount of the gas generative potential obtained by Rock-Eval is only around one tenth of the calculated value by the mass balance of kerogen elements at the same thermal evolutionary stage,while those by Py-GC and gold-tube sealing simulation are intervenient between the above two. The utmost of gas generative potential at the over 1.3% Ro stage is around 60-90 m3/t TOC, therefore, the amount of gas generation obtained by Rock-Eval is the minimum of gas generative potential, while that by the mass-balance calculation of kerogen elements is the maximum that the actual amount of gas generation should not exceed.

  4. Affine functors and duality

    OpenAIRE

    J. Navarro; Sancho, C.; Sancho, P.

    2009-01-01

    A functor of sets $\\mathbb X$ over the category of $K$-commutative algebras is said to be an affine functor if its functor of functions, $\\mathbb A_{\\mathbb X}$, is reflexive and $\\mathbb X=\\Spec \\mathbb A_{\\mathbb X}$. We prove that affine functors are equal to a direct limit of affine schemes and that affine schemes, formal schemes, the completion of affine schemes along a closed subscheme, etc., are affine functors. Endowing an affine functor $\\mathbb X$ with a functor of monoids structure...

  5. Structure of classical affine and classical affine fractional W-algebras

    International Nuclear Information System (INIS)

    We introduce a classical BRST complex (See Definition 3.2.) and show that one can construct a classical affine W-algebra via the complex. This definition clarifies that classical affine W-algebras can be considered as quasi-classical limits of quantum affine W-algebras. We also give a definition of a classical affine fractional W-algebra as a Poisson vertex algebra. As in the classical affine case, a classical affine fractional W-algebra has two compatible λ-brackets and is isomorphic to an algebra of differential polynomials as a differential algebra. When a classical affine fractional W-algebra is associated to a minimal nilpotent, we describe explicit forms of free generators and compute λ-brackets between them. Provided some assumptions on a classical affine fractional W-algebra, we find an infinite sequence of integrable systems related to the algebra, using the generalized Drinfel’d and Sokolov reduction

  6. Transcriptional Landscape of Cardiomyocyte Maturation

    Directory of Open Access Journals (Sweden)

    Hideki Uosaki

    2015-11-01

    Full Text Available Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM differentiation. However, control of the CM maturation that is subsequently required to generate adult myocytes remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs, which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStatCM that indexes CM maturation status. MatStatCM reveals that pluripotent-stem-cell-derived CMs mature early in culture but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation.

  7. Dual Affine invariant points

    OpenAIRE

    Meyer, Mathieu; Schuett, Carsten; Werner, Elisabeth M.

    2013-01-01

    An affine invariant point on the class of convex bodies in R^n, endowed with the Hausdorff metric, is a continuous map p which is invariant under one-to-one affine transformations A on R^n, that is, p(A(K))=A(p(K)). We define here the new notion of dual affine point q of an affine invariant point p by the formula q(K^{p(K)})=p(K) for every convex body K, where K^{p(K)} denotes the polar of K with respect to p(K). We investigate which affine invariant points do have a dual point, whether this ...

  8. Activation of high and low affinity dopamine receptors generates a closed loop that maintains a conductance ratio and its activity correlate

    Directory of Open Access Journals (Sweden)

    Ryan M Hooper

    2013-10-01

    Full Text Available Neuromodulators alter network output and have the potential to destabilize a circuit. The mechanisms maintaining stability in the face of neuromodulation are not well described. Using the pyloric network in the crustacean stomatogastric nervous system, we show that dopamine (DA does not simply alter circuit output, but activates a closed loop in which DA-induced alterations in circuit output consequently drive a change in an ionic conductance to preserve a conductance ratio and its activity correlate. DA acted at low affinity type 1 receptors (D1Rs to induce an immediate modulatory decrease in the transient potassium current (IA of a pyloric neuron. This, in turn, advanced the activity phase of that component neuron, which disrupted its network function and thereby destabilized the circuit. DA simultaneously acted at high affinity D1Rs on the same neuron to confer activity-dependence upon the hyperpolarization activated current (Ih such that the DA-induced changes in activity subsequently reduced Ih. This DA-enabled, activity-dependent, intrinsic plasticity exactly compensated for the modulatory decrease in IA to restore the IA:Ih ratio and neuronal activity phase, thereby closing an open loop created by the modulator. Activation of closed loops to preserve conductance ratios may represent a fundamental operating principle neuromodulatory systems use to ensure stability in their target networks.

  9. Affine Grassmann codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Beelen, Peter; Ghorpade, Sudhir Ramakant

    2010-01-01

    We consider a new class of linear codes, called affine Grassmann codes. These can be viewed as a variant of generalized Reed-Muller codes and are closely related to Grassmann codes.We determine the length, dimension, and the minimum distance of any affine Grassmann code. Moreover, we show that...... affine Grassmann codes have a large automorphism group and determine the number of minimum weight codewords....

  10. Rational development of high-affinity T-cell receptor-like antibodies.

    Science.gov (United States)

    Stewart-Jones, Guillaume; Wadle, Andreas; Hombach, Anja; Shenderov, Eugene; Held, Gerhard; Fischer, Eliane; Kleber, Sascha; Nuber, Natko; Stenner-Liewen, Frank; Bauer, Stefan; McMichael, Andrew; Knuth, Alexander; Abken, Hinrich; Hombach, Andreas A; Cerundolo, Vincenzo; Jones, E Yvonne; Renner, Christoph

    2009-04-01

    T-cell interaction with a target cell is a key event in the adaptive immune response and primarily driven by T-cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes. TCR avidity for a given pMHC is determined by number of MHC molecules, availability of coreceptors, and TCR affinity for MHC or peptide, respectively, with peptide recognition being the most important factor to confer target specificity. Here we present high-resolution crystal structures of 2 Fab antibodies in complex with the immunodominant NY-ESO-1(157-165) peptide analogue (SLLMWITQV) presented by HLA-A*0201 and compare them with a TCR recognizing the same pMHC. Binding to the central methionine-tryptophan peptide motif and orientation of binding were almost identical for Fabs and TCR. As the MW "peg" dominates the contacts between Fab and peptide, we estimated the contributions of individual amino acids between the Fab and peptide to provide the rational basis for a peptide-focused second-generation, high-affinity antibody library. The final Fab candidate achieved better peptide binding by 2 light-chain mutations, giving a 20-fold affinity improvement to 2-4 nM, exceeding the affinity of the TCR by 1,000-fold. The high-affinity Fab when grafted as recombinant TCR on T cells conferred specific killing of HLA-A*0201/NY-ESO-1(157-165) target cells. In summary, we prove that affinity maturation of antibodies mimicking a TCR is possible and provide a strategy for engineering high-affinity antibodies that can be used in targeting specific pMHC complexes for diagnostic and therapeutic purposes. PMID:19307587

  11. Quantifying evolutionary constraints on B cell affinity maturation

    OpenAIRE

    McCoy, Connor O.; Bedford, Trevor; Minin, Vladimir N.; Bradley, Philip; Robins, Harlan; Frederick A. Matsen IV

    2014-01-01

    The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through high-throughput sequencing. Here, we develop modern statistical molecular evolution methods for the analysis of B cell sequence data, and then apply them to a very deep short-read data set of B cell receptors. We find that the substitution process is conserved acros...

  12. Quantifying evolutionary constraints on B-cell affinity maturation.

    Science.gov (United States)

    McCoy, Connor O; Bedford, Trevor; Minin, Vladimir N; Bradley, Philip; Robins, Harlan; Matsen, Frederick A

    2015-09-01

    The antibody repertoire of each individual is continuously updated by the evolutionary process of B-cell receptor (BCR) mutation and selection. It has recently become possible to gain detailed information concerning this process through high-throughput sequencing. Here, we develop modern statistical molecular evolution methods for the analysis of B-cell sequence data, and then apply them to a very deep short-read dataset of BCRs. We find that the substitution process is conserved across individuals but varies significantly across gene segments. We investigate selection on BCRs using a novel method that side-steps the difficulties encountered by previous work in differentiating between selection and motif-driven mutation; this is done through stochastic mapping and empirical Bayes estimators that compare the evolution of in-frame and out-of-frame rearrangements. We use this new method to derive a per-residue map of selection, which provides a more nuanced view of the constraints on framework and variable regions. PMID:26194758

  13. Quantifying evolutionary constraints on B-cell affinity maturation

    OpenAIRE

    McCoy, Connor O.; Bedford, Trevor; Minin, Vladimir N.; Bradley, Philip; Robins, Harlan; Frederick A Matsen

    2015-01-01

    The antibody repertoire of each individual is continuously updated by the evolutionary process of B-cell receptor (BCR) mutation and selection. It has recently become possible to gain detailed information concerning this process through high-throughput sequencing. Here, we develop modern statistical molecular evolution methods for the analysis of B-cell sequence data, and then apply them to a very deep short-read dataset of BCRs. We find that the substitution process is conserved across indiv...

  14. Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, Timothy A.; Chevalier, Aaron; Song, Yifan; Dreyfus, Cyrille; Fleishman, Sarel J.; De Mattos, Cecilia; Myers, Chris A.; Kamisetty, Hetunandan; Blair, Patrick; Wilson, Ian A.; Baker, David (UWASH); (Scripps); (NRL)

    2012-06-19

    We show that comprehensive sequence-function maps obtained by deep sequencing can be used to reprogram interaction specificity and to leapfrog over bottlenecks in affinity maturation by combining many individually small contributions not detectable in conventional approaches. We use this approach to optimize two computationally designed inhibitors against H1N1 influenza hemagglutinin and, in both cases, obtain variants with subnanomolar binding affinity. The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a potency that rivals that of several human monoclonal antibodies, demonstrating that computational design followed by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility.

  15. Affine and Projective Geometry

    CERN Document Server

    Bennett, M K

    1995-01-01

    An important new perspective on AFFINE AND PROJECTIVE GEOMETRY. This innovative book treats math majors and math education students to a fresh look at affine and projective geometry from algebraic, synthetic, and lattice theoretic points of view. Affine and Projective Geometry comes complete with ninety illustrations, and numerous examples and exercises, covering material for two semesters of upper-level undergraduate mathematics. The first part of the book deals with the correlation between synthetic geometry and linear algebra. In the second part, geometry is used to introduce lattice theory

  16. Complete algebraic vector fields on affine surfaces

    OpenAIRE

    Kaliman, Shulim; Kutzschebauch, Frank; Leuenberger, Matthias

    2014-01-01

    Let $\\AAutH (X)$ be the subgroup of the group $\\AutH (X)$ of holomorphic automorphisms of a normal affine algebraic surface $X$ generated by elements of flows associated with complete algebraic vector fields. Our main result is a classification of all normal affine algebraic surfaces $X$ quasi-homogeneous under $\\AAutH (X)$ in terms of the dual graphs of the boundaries $\\bX \\setminus X$ of their SNC-completions $\\bX$.

  17. Affine dynamics with torsion

    Energy Technology Data Exchange (ETDEWEB)

    Gueltekin, Kemal [Izmir Institute of Technology, Department of Physics, Izmir (Turkey)

    2016-03-15

    In this study, we give a thorough analysis of a general affine gravity with torsion. After a brief exposition of the affine gravities considered by Eddington and Schroedinger, we construct and analyze different affine gravities based on the determinants of the Ricci tensor, the torsion tensor, the Riemann tensor, and their combinations. In each case we reduce equations of motion to their simplest forms and give a detailed analysis of their solutions. Our analyses lead to the construction of the affine connection in terms of the curvature and torsion tensors. Our solutions of the dynamical equations show that the curvature tensors at different points are correlated via non-local, exponential rescaling factors determined by the torsion tensor. (orig.)

  18. Affine and degenerate affine BMW algebras: Actions on tensor space

    CERN Document Server

    Daugherty, Zajj; Virk, Rahbar

    2012-01-01

    The affine and degenerate affine Birman-Murakami-Wenzl (BMW) algebras arise naturally in the context of Schur-Weyl duality for orthogonal and symplectic quantum groups and Lie algebras, respectively. Cyclotomic BMW algebras, affine and cyclotomic Hecke algebras, and their degenerate versions are quotients. In this paper we explain how the affine and degenerate affine BMW algebras are tantalizers (tensor power centralizer algebras) by defining actions of the affine braid group and the degenerate affine braid algebra on tensor space and showing that, in important cases, these actions induce actions of the affine and degenerate affine BMW algebras. We then exploit the connection to quantum groups and Lie algebras to determine universal parameters for the affine and degenerate affine BMW algebras. Finally, we show that the universal parameters are central elements--the higher Casimir elements for orthogonal and symplectic enveloping algebras and quantum groups.

  19. Selected aspects of tiny vetch [Vicia hirsuta (L. Gray S.F.] seed ecology: generative reproduction and effects of seed maturity and seed storage on seed germination

    Directory of Open Access Journals (Sweden)

    Magdalena Kucewicz

    2012-12-01

    Full Text Available Vicia hirsuta (L. Gray S.F. (tiny vetch is a common and persistent segetal weed. Tiny vetch seeds and pods reach different stages of maturity during the crop harvest season. Some seeds that mature before cereal harvest are shed in the field and deposited in the soil seed bank, while others become incorporated into seed material. The objective of this study was to describe selected aspects of tiny vetch seed ecology: to determine the rate of individual reproduction of vetch plants growing in winter and spring grain crops and to evaluate the germination of seeds at different stages of maturity, subject to storage conditions. The seeds and pods of V. hirsuta were sorted according to their development stages at harvest and divided into two groups. The first group was stored under laboratory conditions for two months. In the autumn of the same year, the seeds were subjected to germination tests. The remaining seeds were stored in a storeroom, and were planted in soil in the spring. The germination rate was evaluated after 8 months of storage. Potential productivity (developed pods and flowers, fruit buds was higher in plants fruiting in winter wheat than in spring barley. Vetch plants produced around 17-26% more pods (including cracked, mature, greenish-brown and green pods and around 25% less buds in winter wheat than in spring barley. Immature seeds were characterized by the highest germination capacity. Following storage under laboratory conditions and stratification in soil, mature seeds germinated at a rate of several percent. After storage in a storeroom, seeds at all three development stages broke dormancy at a rate of 72- 75%. The high germination power of tiny vetch seeds stored in a storeroom indicates that this plant can be classified as an obligatory speirochoric weed species.

  20. Classical affine W-algebras associated to Lie superalgebras

    International Nuclear Information System (INIS)

    In this paper, we prove classical affine W-algebras associated to Lie superalgebras (W-superalgebras), which can be constructed in two different ways: via affine classical Hamiltonian reductions and via taking quasi-classical limits of quantum affine W-superalgebras. Also, we show that a classical finite W-superalgebra can be obtained by a Zhu algebra of a classical affine W-superalgebra. Using the definition by Hamiltonian reductions, we find free generators of a classical W-superalgebra associated to a minimal nilpotent. Moreover, we compute generators of the classical W-algebra associated to spo(2|3) and its principal nilpotent. In the last part of this paper, we introduce a generalization of classical affine W-superalgebras called classical affine fractional W-superalgebras. We show these have Poisson vertex algebra structures and find generators of a fractional W-superalgebra associated to a minimal nilpotent

  1. Classical affine W-algebras associated to Lie superalgebras

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Uhi Rinn, E-mail: uhrisu1@math.snu.ac.kr [Department of Mathematical Sciences, Seoul National University, GwanAkRo 1, Gwanak-Gu, Seoul 151-747 (Korea, Republic of)

    2016-02-15

    In this paper, we prove classical affine W-algebras associated to Lie superalgebras (W-superalgebras), which can be constructed in two different ways: via affine classical Hamiltonian reductions and via taking quasi-classical limits of quantum affine W-superalgebras. Also, we show that a classical finite W-superalgebra can be obtained by a Zhu algebra of a classical affine W-superalgebra. Using the definition by Hamiltonian reductions, we find free generators of a classical W-superalgebra associated to a minimal nilpotent. Moreover, we compute generators of the classical W-algebra associated to spo(2|3) and its principal nilpotent. In the last part of this paper, we introduce a generalization of classical affine W-superalgebras called classical affine fractional W-superalgebras. We show these have Poisson vertex algebra structures and find generators of a fractional W-superalgebra associated to a minimal nilpotent.

  2. Optimizing Arteriovenous Fistula Maturation

    OpenAIRE

    Zangan, Steven M.; Falk, Abigail

    2009-01-01

    Autogenous arteriovenous fistulas are the preferred vascular access in patients undergoing hemodialysis. Increasing fistula prevalence depends on increasing fistula placement, improving the maturation of fistula that fail to mature and enhancing the long-term patency of mature fistula. Percutaneous methods for optimizing arteriovenous fistula maturation will be reviewed.

  3. Determination of trace glucose and forecast of human diseases by affinity adsorption solid substrate room temperature phosphorimetry based on Triticum valgaris lectin labeled with 4.0-generation dendrimers

    Science.gov (United States)

    Li, Zhiming; Zhu, Guohui; Liu, Jiaming; Lu, Qiaomei; Yang, Minlan; Wu, Hong; Shi, Xiumei; Chen, Xinhua

    2007-08-01

    A new phosphorescence labeling reagent Triton-100X-4.0G-D (4.0G-D refers to 4.0-generation dendrimers) was found. Quantitative specific affinity adsorption (AA) reaction between Triton-100X-4.0G-D-WGA and glucose (G) was carried out on the surface of nitrocellulose membrane (NCM), and the Δ Ip of the product of AA reaction was linear correlation to the content of G. Based on the facts above, a new method for the determination of trace G was established by WGA labeled with Triton-100X-4.0G-D affinity adsorption solid substrate room temperature phosphorimetry (Triton-100X-4.0G-D-WGA-AA-SS-RTP). This research showed that AA-SS-RTP for either direct method or sandwich method could combine very well the characteristics of both the high sensitivity of SS-RTP and the specificity of the AA reaction. Detection limits (LD) were 0.24 fg spot -1 for direct method and 0.18 fg spot -1 for sandwich method, indicating both of them were of high sensitivity. The method has been applied to the determination of the content of G in human serum, and the results were coincided with those obtained by glucose oxidize enzyme method. It can also be applied to forecast accurately some human diseases, such as primary hepatic carcinoma, cirrhosis, acute and chronic hepatitis, transfer hepatocellular, etc. Meanwhile, the mechanism for the determination of G with AA-SS-RTP was discussed.

  4. Generation of a panel of high affinity antibodies and development of a biosensor-based immunoassay for the detection of okadaic acid in shellfish.

    Science.gov (United States)

    Le Berre, Marie; Kilcoyne, Michelle; Kane, Marian

    2015-09-01

    Okadaic acid (OA) and its derivatives, DTX-1 and DTX-2, are marine biotoxins associated with diarrhetic shellfish poisoning. Routine monitoring of these toxins relies on the mouse bioassay. However, due to the technical unreliability and animal usage of this bioassay, there is always a need for convenient and reliable alternative assay methods. A panel of monoclonal antibodies against OA was generated and the most suitable was selected for biosensor-based assay development using surface plasmon resonance. The cross reactivity of the selected antibody with DTX-1 was found to be 73%, confirming the antibody suitability for both OA and DTX detection. The OA and derivative assay was designed as an inhibition assay covering the concentrations 1-75 ng/ml, with a sensitivity of 22.4 ng/ml. The assay was highly reproducible and preliminary validation showed no matrix interference from mussel extracts and good recovery of added standard in mussel extracts, with %CV of <9.3%. This assay could provide a useful and convenient screening tool for OA and its derivatives with a comprehensive extraction protocol for shellfish monitoring programmes. PMID:26169671

  5. Smooth affine shear tight frames: digitization and applications

    Science.gov (United States)

    Zhuang, Xiaosheng

    2015-08-01

    In this paper, we mainly discuss one of the recent developed directional multiscale representation systems: smooth affine shear tight frames. A directional wavelet tight frame is generated by isotropic dilations and translations of directional wavelet generators, while an affine shear tight frame is generated by anisotropic dilations, shears, and translations of shearlet generators. These two tight frames are actually connected in the sense that the affine shear tight frame can be obtained from a directional wavelet tight frame through subsampling. Consequently, an affine shear tight frame indeed has an underlying filter bank from the MRA structure of its associated directional wavelet tight frame. We call such filter banks affine shear filter banks, which can be designed completely in the frequency domain. We discuss the digitization of affine shear filter banks and their implementations: the forward and backward digital affine shear transforms. Redundancy rate and computational complexity of digital affine shear transforms are also investigated in this paper. Numerical experiments and comparisons in image/video processing show the advantages of digital affine shear transforms over many other state-of-art directional multiscale representation systems.

  6. Affine and degenerate affine BMW algebras: The center

    CERN Document Server

    Daugherty, Zajj; Virk, Rahbar

    2011-01-01

    The degenerate affine and affine BMW algebras arise naturally in the context of Schur-Weyl duality for orthogonal and symplectic Lie algebras and quantum groups, respectively. Cyclotomic BMW algebras, affine Hecke algebras, cyclotomic Hecke algebras, and their degenerate versions are quotients. In this paper the theory is unified by treating the orthogonal and symplectic cases simultaneously; we make an exact parallel between the degenerate affine and affine cases via a new algebra which takes the role of the affine braid group for the degenerate setting. A main result of this paper is an identification of the centers of the affine and degenerate affine BMW algebras in terms of rings of symmetric functions which satisfy a "cancellation property" or "wheel condition" (in the degenerate case, a reformulation of a result of Nazarov). Miraculously, these same rings also arise in Schubert calculus, as the cohomology and K-theory of isotropic Grassmanians and symplectic loop Grassmanians. We also establish new inte...

  7. Effect of convective transport in porous media on the conditions of organic matter maturation and generation of hydrocarbons in trap rocks complexes

    Science.gov (United States)

    Yurie Khachay, Professor; Mindubaev, Mansur

    2016-04-01

    One of the main problems of the study of the intrusion thermal effects on the maturation of the organic matter is to estimate the volume, intensity, thermal effects of the intrusion and its redistribution in porous media by convection. A numerical algorithm for solving the problem of the developed convection in two-dimensional and three-dimensional models of the porous medium depending on the incline angle is developed. It is defined that the convective stability in the medium decreases with increasing incline angle. It was found that depending on the incline angle the structure of convection from many cells for a flat horizontal layer changes and it transfers to more elongated structures along the layer. It is shown that depending on the incline angles, invading sill and imbedding volume of the porous medium it can be realized either stationary or non-stationary convection that provides a principal different thermal conditions of hydrocarbons maturation in the motherboard porous medium. We give numerical examples of the influence of the incline angle on the flow structure inside the porous inclusion. By the stationary convection the volume of the boundary layers between the convective sells increases. That can lead to increasing of the part of motherboard rocks that are outer the temperature conditions of oil catalysis and as a consequence to the overestimation of the deposits.

  8. Hierarchical Affinity Propagation

    CERN Document Server

    Givoni, Inmar; Frey, Brendan J

    2012-01-01

    Affinity propagation is an exemplar-based clustering algorithm that finds a set of data-points that best exemplify the data, and associates each datapoint with one exemplar. We extend affinity propagation in a principled way to solve the hierarchical clustering problem, which arises in a variety of domains including biology, sensor networks and decision making in operational research. We derive an inference algorithm that operates by propagating information up and down the hierarchy, and is efficient despite the high-order potentials required for the graphical model formulation. We demonstrate that our method outperforms greedy techniques that cluster one layer at a time. We show that on an artificial dataset designed to mimic the HIV-strain mutation dynamics, our method outperforms related methods. For real HIV sequences, where the ground truth is not available, we show our method achieves better results, in terms of the underlying objective function, and show the results correspond meaningfully to geographi...

  9. Affinity driven social networks

    Science.gov (United States)

    Ruyú, B.; Kuperman, M. N.

    2007-04-01

    In this work we present a model for evolving networks, where the driven force is related to the social affinity between individuals of a population. In the model, a set of individuals initially arranged on a regular ordered network and thus linked with their closest neighbors are allowed to rearrange their connections according to a dynamics closely related to that of the stable marriage problem. We show that the behavior of some topological properties of the resulting networks follows a non trivial pattern.

  10. Affine General Equilibrium Models

    OpenAIRE

    Bjørn Eraker

    2008-01-01

    No-arbitrage models are extremely flexible modelling tools but often lack economic motivation. This paper describes an equilibrium consumption-based CAPM framework based on Epstein-Zin preferences, which produces analytic pricing formulas for stocks and bonds under the assumption that macro growth rates follow affine processes. This allows the construction of equilibrium pricing formulas while maintaining the same flexibility of state dynamics as in no-arbitrage models. In demonstrating the a...

  11. Gaussian Affine Feature Detector

    OpenAIRE

    Xu, Xiaopeng; Zhang, Xiaochun

    2011-01-01

    A new method is proposed to get image features' geometric information. Using Gaussian as an input signal, a theoretical optimal solution to calculate feature's affine shape is proposed. Based on analytic result of a feature model, the method is different from conventional iterative approaches. From the model, feature's parameters such as position, orientation, background luminance, contrast, area and aspect ratio can be extracted. Tested with synthesized and benchmark data, the method achieve...

  12. In- and outdoor reproduction of first generation common sole Solea solea under a natural photothermal regime: Temporal progression of sexual maturation assessed by monitoring plasma steroids and gonadotropin mRNA expression.

    Science.gov (United States)

    Palstra, A P; Blok, M C; Kals, J; Blom, E; Tuinhof-Koelma, N; Dirks, R P; Forlenza, M; Blonk, R J W

    2015-09-15

    Reproduction of many temperate fishes is seasonal and maturation and spawning of gametes are under photothermal control. Reproductive success of first generation (G1) common sole Solea solea in captivity has been low. In this study, the sexual maturation status has been assessed during the prespawning months in G1 sole that were housed (a) outdoor under the natural photoperiod and temperature, or (b) indoor under artificial photothermal induction. Maturation was assessed in male and female G1 broodstock in November as controls, after which the remaining population was divided over two outdoor flow-through tanks placed in a pond and two indoor recirculating aquaculture system (RAS) tanks. Subsequently, maturation status (gonadosomatic index GSI and plasma levels of testosterone T and 17β-estradiol E2) was assessed in one tank for each condition in January, February and during spawning in early April, while fish in the other tank were not disturbed in achieving reproductive success. Quantitative real-time PCR was performed to determine species-specific gonadotropin mRNA expression in females. Successful G1 spawning and egg fertilisation occurred in all experimental tanks. Gonadal development was similar under both conditions. Higher E2 and T levels were found in indoor housed females. Gonadotropin expression revealed similar profiles between outdoor and indoor housed females. G1 sole could be reproduced in the outdoor tanks under the natural photoperiod and in the indoor tanks under artificial simulation of this regime that includes a potentially crucial chilling period of 2-3 months at 5-7 °C. PMID:25583580

  13. On the Affine Isoperimetric Inequalities

    Indian Academy of Sciences (India)

    Wuyang Yu; Gangsong Leng

    2011-11-01

    We obtain an isoperimetric inequality which estimate the affine invariant -surface area measure on convex bodies. We also establish the reverse version of -Petty projection inequality and an affine isoperimetric inequality of $_{-p}K$.

  14. Insufficient Generation of Mycobactericidal Mediators and Inadequate Level of Phagosomal Maturation Are Related with Susceptibility to Virulent Mycobacterium tuberculosis Infection in Mouse Macrophages.

    Science.gov (United States)

    Lee, Hyo-Ji; Ko, Hyun-Jeong; Jung, Yu-Jin

    2016-01-01

    Tuberculosis is caused by Mycobacterium tuberculosis infection, and it remains major life-threatening infectious diseases worldwide. Although, M. tuberculosis has infected one-third of the present human population, only 5-10% of immunocompetent individuals are genetically susceptible to tuberculosis. All inbred strains of mice are susceptible to tuberculosis; however, some mouse strains are much more susceptible than others. In a previous report, we showed that Th1-mediated immunity was not responsible for the differential susceptibility between mouse models. To examine whether these susceptibility differences between inbred mouse strains are due to the insufficient production of effector molecules in the early stage of innate immunity, we investigated mycobacteriostatic function of bone marrow-derived macrophages (BMDMs) in resistant (BALB/c and C57BL/6) and susceptible strains (DBA/2) that were infected with virulent M. tuberculosis (H37Rv) or attenuated M. tuberculosis (H37Ra). The growth rate of virulent M. tuberculosis in infected cells was significantly higher in DBA/2 BMDMs, whereas the growth of the attenuated strain was similar in the three inbred mouse BMDM strains. In addition, the death rate of M. tuberculosis-infected cells increased with the infectious dose when DBA/2 BMDMs were infected with H37Rv. The intracellular reactive oxygen species level was lower in DBA/2 BMDMs that were infected with virulent M. tuberculosis at an early post-infection time point. The expression levels of phagosomal maturation markers, including early endosomal antigen-1 (EEA1) and lysosome-associated membrane protein-1 (LAMP-1), were significantly decreased in DBA/2 BMDM that were infected with virulent M. tuberculosis, whereas IFNγ-treatment restored the phagosomal maturation activity. The nitric oxide (NO) production levels were also significantly lower in DBA/2 BMDMs that were infected with virulent H37Rv at late post-infection points; however, this was not observed

  15. Insufficient generation of mycobactericidal mediators and inadequate level of phagosomal maturation are related with susceptibility to virulent Mycobacterium tuberculosis infection in mouse macrophages

    Directory of Open Access Journals (Sweden)

    Hyo-Ji eLee

    2016-04-01

    Full Text Available Tuberculosis is caused by Mycobacterium tuberculosis (M. tuberculosis, Mtb infection, and it remains major life-threatening infectious diseases worldwide. Although Mtb has infected one-third of the present human population, only 5-10% of immunocompetent individuals are genetically susceptible to tuberculosis. All inbred strains of mice are susceptible to tuberculosis; however, some mouse strains are much more susceptible than others. In a previous report, we showed that Th1-mediated immunity was not responsible for the differential susceptibility between mouse models. To examine whether these susceptibility differences between inbred mouse strains are due to the insufficient production of effector molecules in the early stage of innate immunity, we investigated mycobacteriostatic function of bone marrow-derived macrophages (BMDMs in resistant (BALB/c and C57BL/6 and susceptible strains (DBA/2 that were infected with virulent Mtb (H37Rv or attenuated Mtb (H37Ra. The growth rate of virulent Mtb in infected cells was significantly higher in DBA/2 BMDMs, whereas the growth of the attenuated strain was similar in the three inbred mouse BMDM strains. In addition, the death rate of Mtb-infected cells increased with the infectious dose when DBA/2 BMDMs were infected with H37Rv. The intracellular reactive oxygen species (ROS level was lower in DBA/2 BMDMs that were infected with virulent Mtb at an early post-infection time point. The expression levels of phagosomal maturation markers, including early endosomal antigen-1 (EEA1 and lysosome-associated membrane protein-1 (LAMP-1, were significantly decreased in DBA/2 BMDM that were infected with virulent Mtb, whereas IFNγ-treatment restored the phagosomal maturation activity. The nitric oxide (NO production levels were also significantly lower in DBA/2 BMDMs that were infected with virulent H37Rv at late post infection points; however, this was not observed with the attenuated H37Ra strain. Furthermore

  16. Maturity and maturity models in lean construction

    Directory of Open Access Journals (Sweden)

    Claus Nesensohn

    2014-03-01

    Full Text Available In recent years there has been an increasing interest in maturity models in management-related disciplines; which reflects a growing recognition that becoming more mature and having a model to guide the route to maturity can help organisations in managing major transformational change. Lean Construction (LC is an increasingly important improvement approach that organisations seek to embed. This study explores how to apply the maturity models to LC. Hence the attitudes, opinions and experiences of key industry informants with high levels of knowledge of LC were investigated. To achieve this, a review of maturity models was conducted, and data for the analysis was collected through a sequential process involving three methods. First a group interview with seven key informants. Second a follow up discussion with the same individuals to investigate some of the issues raised in more depth. Third an online discussion held via LinkedIn in which members shared their views on some of the results. Overall, we found that there is a lack of common understanding as to what maturity means in LC, though there is general agreement that the concept of maturity is a suitable one to reflect the path of evolution for LC within organisations.

  17. Adjoint affine fusion and tadpoles

    OpenAIRE

    Urichuk, Andrew; Walton, Mark A.

    2016-01-01

    We study affine fusion with the adjoint representation. For simple Lie algebras, elementary and universal formulas determine the decomposition of a tensor product of an integrable highest-weight representation with the adjoint representation. Using the (refined) affine depth rule, we prove that equally striking results apply to adjoint affine fusion. For diagonal fusion, a coefficient equals the number of nonzero Dynkin labels of the relevant affine highest weight, minus 1. A nice lattice-pol...

  18. The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Jie Luo

    Full Text Available The type 3 adenylyl cyclase (AC3 is localized to olfactory cilia in the main olfactory epithelium (MOE and primary cilia in the adult mouse brain. Although AC3 has been strongly implicated in odor perception and olfactory sensory neuron (OSN targeting, its role in granule cells (GCs, the most abundant interneurons in the main olfactory bulb (MOB, remains largely unknown. Here, we report that the deletion of AC3 leads to a significant reduction in the size of the MOB as well as the level of adult neurogenesis. The cell proliferation and cell cycle in the subventricular zone (SVZ, however, are not suppressed in AC3-/- mice. Furthermore, AC3 deletion elevates the apoptosis of GCs and disrupts the maturation of newly formed GCs. Collectively, our results identify a fundamental role for AC3 in the development of adult-born GCs in the MOB.

  19. Gaussian Affine Feature Detector

    CERN Document Server

    Xu, Xiaopeng

    2011-01-01

    A new method is proposed to get image features' geometric information. Using Gaussian as an input signal, a theoretical optimal solution to calculate feature's affine shape is proposed. Based on analytic result of a feature model, the method is different from conventional iterative approaches. From the model, feature's parameters such as position, orientation, background luminance, contrast, area and aspect ratio can be extracted. Tested with synthesized and benchmark data, the method achieves or outperforms existing approaches in term of accuracy, speed and stability. The method can detect small, long or thin objects precisely, and works well under general conditions, such as for low contrast, blurred or noisy images.

  20. Modulation of Gonadotropin-Releasing Hormone Pulse Generator Sensitivity to Progesterone Inhibition in Hyperandrogenic Adolescent Girls—Implications for Regulation of Pubertal Maturation

    OpenAIRE

    Blank, Susan K.; McCartney, Christopher R.; Chhabra, Sandhya; Helm, Kristin D.; Eagleson, Christine A.; Chang, R. Jeffrey; Marshall, John C.

    2009-01-01

    Context: Adult women with polycystic ovary syndrome (PCOS) have decreased GnRH pulse generator sensitivity to progesterone (P)-mediated slowing. This defect is androgen mediated because it is reversed with androgen receptor blockade. Adolescent hyperandrogenism often precedes PCOS.

  1. Affinity Purification of Insulin by Peptide-Ligand Affinity Chromatography

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The affinity heptapeptide (HWWWPAS) for insulin, selected from phage display library,was coupled to EAH Sepharose 4B gel and packed to a 1-mL column. The column was used for the affinity purification of insulin from protein mixture and commercial insulin preparation. It was observed that the minor impurity in the commercial insulin was removed by the affinity chromatography. Nearly 40 mg of insulin could be purified with the 1-mL affinity column. The results revealed the high specificity and capacity of the affinity column for insulin purification. Moreover, based on the analysis of the amino acids in the peptide sequence, shorter peptides were designed and synthesized for insulin chromatography. As a result, HWWPS was found to be a good alternative to HWWWPAS, while the other two peptides with three or four amino acids showed weak affinity for insulin. The results indicated that the peptide sequence of HWWWPAS was quite conservative for specific binding of insulin.

  2. An affine framework for analytical mechanics

    OpenAIRE

    Urbanski, Pawel

    2003-01-01

    An affine Cartan calculus is developed. The concepts of special affine bundles and special affine duality are introduced. The canonical isomorphisms, fundamental for Lagrangian and Hamiltonian formulations of the dynamics in the affine setting are proved.

  3. Adjoint affine fusion and tadpoles

    Science.gov (United States)

    Urichuk, Andrew; Walton, Mark A.

    2016-06-01

    We study affine fusion with the adjoint representation. For simple Lie algebras, elementary and universal formulas determine the decomposition of a tensor product of an integrable highest-weight representation with the adjoint representation. Using the (refined) affine depth rule, we prove that equally striking results apply to adjoint affine fusion. For diagonal fusion, a coefficient equals the number of nonzero Dynkin labels of the relevant affine highest weight, minus 1. A nice lattice-polytope interpretation follows and allows the straightforward calculation of the genus-1 1-point adjoint Verlinde dimension, the adjoint affine fusion tadpole. Explicit formulas, (piecewise) polynomial in the level, are written for the adjoint tadpoles of all classical Lie algebras. We show that off-diagonal adjoint affine fusion is obtained from the corresponding tensor product by simply dropping non-dominant representations.

  4. Adjoint affine fusion and tadpoles

    CERN Document Server

    Urichuk, Andrew

    2016-01-01

    We study affine fusion with the adjoint representation. For simple Lie algebras, elementary and universal formulas determine the decomposition of a tensor product of an integrable highest-weight representation with the adjoint representation. Using the (refined) affine depth rule, we prove that equally striking results apply to adjoint affine fusion. For diagonal fusion, a coefficient equals the number of nonzero Dynkin labels of the relevant affine highest weight, minus 1. A nice lattice-polytope interpretation follows, and allows the straightforward calculation of the genus-1 1-point adjoint Verlinde dimension, the adjoint affine fusion tadpole. Explicit formulas, (piecewise) polynomial in the level, are written for the adjoint tadpoles of all classical Lie algebras. We show that off-diagonal adjoint affine fusion is obtained from the corresponding tensor product by simply dropping non-dominant representations.

  5. The Flight from Maturity

    OpenAIRE

    Gary B. Gorton; Andrew Metrick; Lei Xie

    2014-01-01

    Why did the failure of Lehman Brothers make the financial crisis dramatically worse? The financial crisis was a process of a build-up of risk during the crisis prior to the Lehman failure. Market participants tried to preserve an option or exit by shortening maturities - the "flight from maturity". With increasingly short maturities, lenders created the possibility of fast exit. The failure of Lehman Brothers was the tipping point of this build-up of systemic fragility. We produce a chronolog...

  6. Audit Maturity Model

    Directory of Open Access Journals (Sweden)

    Bhattacharya Uttam

    2014-01-01

    Full Text Available Today it is crucial for organizations to pay even greater attention on quality management as the importance of this function in achieving ultimate business objectives is increasingly becoming clearer. Importance of the Quality Management (QM Function in achieving basic need by ensuring compliance with Capability Maturity Model Integrated (CMMI / International Organization for Standardization (ISO is a basic demand from business nowadays. However, QM Function and its processes need to be made much more mature to prevent delivery outages and to achieve business excellence through their review and auditing capability. Many organizations now face challenges in determining the maturity of the QM group along with the service offered by them and the right way to elevate the maturity of the same. The objective of this whitepaper is to propose a new model –the Audit Maturity Model (AMM which will provide organizations with a measure of their maturity in quality management in the perspective of auditing, along with recommendations for preventing delivery outage, and identifying risk to achieve business excellence. This will enable organizations to assess QM maturity higher than basic hygiene and will also help them to identify gaps and to take corrective actions for achieving higher maturity levels. Hence the objective is to envisage a new auditing model as a part of organisation quality management function which can be a guide for them to achieve higher level of maturity and ultimately help to achieve delivery and business excellence.

  7. Affine group formulation of the Standard Model coupled to gravity

    International Nuclear Information System (INIS)

    In this work we apply the affine group formalism for four dimensional gravity of Lorentzian signature, which is based on Klauder’s affine algebraic program, to the formulation of the Hamiltonian constraint of the interaction of matter and all forces, including gravity with non-vanishing cosmological constant Λ, as an affine Lie algebra. We use the hermitian action of fermions coupled to gravitation and Yang–Mills theory to find the density weight one fermionic super-Hamiltonian constraint. This term, combined with the Yang–Mills and Higgs energy densities, are composed with York’s integrated time functional. The result, when combined with the imaginary part of the Chern–Simons functional Q, forms the affine commutation relation with the volume element V(x). Affine algebraic quantization of gravitation and matter on equal footing implies a fundamental uncertainty relation which is predicated upon a non-vanishing cosmological constant. -- Highlights: •Wheeler–DeWitt equation (WDW) quantized as affine algebra, realizing Klauder’s program. •WDW formulated for interaction of matter and all forces, including gravity, as affine algebra. •WDW features Hermitian generators in spite of fermionic content: Standard Model addressed. •Constructed a family of physical states for the full, coupled theory via affine coherent states. •Fundamental uncertainty relation, predicated on non-vanishing cosmological constant

  8. Investigation of complexes with bone affinity using the In vivo generator system {sup 166} Dy/{sup 166} Ho; Investigacion de complejos con afinidad osea utilizando el Sistema de Generador in vivo {sup 166} Dy/{sup 166} Ho

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M

    2006-07-01

    The importance of this original research lies in the fact that it has proven that the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system is a stable complex that can be used as a therapeutic radiopharmaceutical. Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. Bone-seeking radiopharmaceuticals such as {sup 166}Ho-DOTMP or {sup 153}Sm-DTMP, have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other hematological malignancies or have shown excellent results in palliative bone metastasis pain therapy, respectively. As lanthanides have similar chemical characteristics the phosphonate with bone affinity (EDTMP) labeled with Dy/Ho can be used for marrow ablation while causing minimal irradiation to normal organs. This in vivo generator system has not been previously reported. The aim of this research was to label EDTMP (ethylene diamine tetramethylene phosphonate) with {sup 166}Dy/{sup 166}Ho; to evaluate the in vitro and in vivo stability of both {sup 166}Dy-EDTMP and {sup 166}Ho-EDTMP complexes when the daughter {sup 166}Ho is formed as a dysprosium decay product; to determine the bone marrow cytotoxic and genotoxic effect in mice and to evaluate, by histopathology, the myeloablative potential of the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system. {sup 166}Dy was obtained by neutron irradiation of enriched {sup 164}Dy{sub 2}O{sub 3} in a TRIGA Mark III reactor. Labeling was carried out in an aqueous phosphate medium at pH 8.0 by addition of {sup 166}DyCl{sub 3} to EDTMP at a molar ratio 1:1.75, with >99 % radiochemical purity, as determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). In vitro studies demonstrated that {sup 166}Dy/{sup 166}Ho-EDTMP is unstable after dilution in saline but stable in human serum with no translocation of the daughter nucleus

  9. Investigation of complexes with bone affinity using the In vivo generator system {sup 166} Dy/{sup 166} Ho; Investigacion de complejos con afinidad osea utilizando el Sistema de Generador in vivo {sup 166} Dy/{sup 166} Ho

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M

    2006-07-01

    The importance of this original research lies in the fact that it has proven that the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system is a stable complex that can be used as a therapeutic radiopharmaceutical. Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. Bone-seeking radiopharmaceuticals such as {sup 166}Ho-DOTMP or {sup 153}Sm-DTMP, have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other hematological malignancies or have shown excellent results in palliative bone metastasis pain therapy, respectively. As lanthanides have similar chemical characteristics the phosphonate with bone affinity (EDTMP) labeled with Dy/Ho can be used for marrow ablation while causing minimal irradiation to normal organs. This in vivo generator system has not been previously reported. The aim of this research was to label EDTMP (ethylene diamine tetramethylene phosphonate) with {sup 166}Dy/{sup 166}Ho; to evaluate the in vitro and in vivo stability of both {sup 166}Dy-EDTMP and {sup 166}Ho-EDTMP complexes when the daughter {sup 166}Ho is formed as a dysprosium decay product; to determine the bone marrow cytotoxic and genotoxic effect in mice and to evaluate, by histopathology, the myeloablative potential of the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system. {sup 166}Dy was obtained by neutron irradiation of enriched {sup 164}Dy{sub 2}O{sub 3} in a TRIGA Mark III reactor. Labeling was carried out in an aqueous phosphate medium at pH 8.0 by addition of {sup 166}DyCl{sub 3} to EDTMP at a molar ratio 1:1.75, with >99 % radiochemical purity, as determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). In vitro studies demonstrated that {sup 166}Dy/{sup 166}Ho-EDTMP is unstable after dilution in saline but stable in human serum with no translocation of the daughter nucleus

  10. Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process

    Directory of Open Access Journals (Sweden)

    Catherine S. Adamson

    2012-01-01

    Full Text Available Protease-mediated maturation of HIV-1 virus particles is essential for virus infectivity. Maturation occurs concomitant with immature virus particle release and is mediated by the viral protease (PR, which sequentially cleaves the Gag and Gag-Pol polyproteins into mature protein domains. Maturation triggers a second assembly event that generates a condensed conical capsid core. The capsid core organizes the viral RNA genome and viral proteins to facilitate viral replication in the next round of infection. The fundamental role of proteolytic maturation in the generation of mature infectious particles has made it an attractive target for therapeutic intervention. Development of small molecules that target the PR active site has been highly successful and nine protease inhibitors (PIs have been approved for clinical use. This paper provides an overview of their development and clinical use together with a discussion of problems associated with drug resistance. The second-half of the paper discusses a novel class of antiretroviral drug termed maturation inhibitors, which target cleavage sites in Gag not PR itself. The paper focuses on bevirimat (BVM the first-in-class maturation inhibitor: its mechanism of action and the implications of naturally occurring polymorphisms that confer reduced susceptibility to BVM in phase II clinical trials.

  11. Measuring project portfolio management maturity

    OpenAIRE

    Hänninen, Kirsti

    2016-01-01

    The thesis is researching portfolio management maturity in organizations that have project type of work. The objective of the thesis is to define what factors affect portfolio management maturity, how the maturity level can be evaluated and create a method for measuring current level of maturity. The thesis also provides maturity level improvement suggestions. Why is maturity measurement useful? The organizations that have project type of work often have some standardized practices. But t...

  12. Infinite transitivity on affine varieties

    OpenAIRE

    Arzhantsev, Ivan; Flenner, Hubert; Kaliman, Shulim; Kutzschebauch, Frank; ZAIDENBERG, MIKHAIL

    2012-01-01

    In this note we survey recent results on automorphisms of affine algebraic varieties, infinitely transitive group actions and flexibility. We present related constructions and examples, and discuss geometric applications and open problems.

  13. Representations of affine Hecke algebras

    CERN Document Server

    Xi, Nanhua

    1994-01-01

    Kazhdan and Lusztig classified the simple modules of an affine Hecke algebra Hq (q E C*) provided that q is not a root of 1 (Invent. Math. 1987). Ginzburg had some very interesting work on affine Hecke algebras. Combining these results simple Hq-modules can be classified provided that the order of q is not too small. These Lecture Notes of N. Xi show that the classification of simple Hq-modules is essentially different from general cases when q is a root of 1 of certain orders. In addition the based rings of affine Weyl groups are shown to be of interest in understanding irreducible representations of affine Hecke algebras. Basic knowledge of abstract algebra is enough to read one third of the book. Some knowledge of K-theory, algebraic group, and Kazhdan-Lusztig cell of Cexeter group is useful for the rest

  14. Affine toric SL(2)-embeddings

    International Nuclear Information System (INIS)

    In the theory of affine SL(2)-embeddings, which was constructed in 1973 by Popov, a locally transitive action of the group SL(2) on a normal affine three-dimensional variety X is determined by a pair (p/q,r), where 0GV//T-hat. In the substantiation of this result a key role is played by Cox's construction in toric geometry. Bibliography: 12 titles

  15. Evolution of an interloop disulfide bond in high-affinity antibody mimics based on fibronectin type III domain and selected by yeast surface display: molecular convergence with single-domain camelid and shark antibodies.

    Science.gov (United States)

    Lipovsek, Dasa; Lippow, Shaun M; Hackel, Benjamin J; Gregson, Melissa W; Cheng, Paul; Kapila, Atul; Wittrup, K Dane

    2007-05-11

    The 10th human fibronectin type III domain ((10)Fn3) is one of several protein scaffolds used to design and select families of proteins that bind with high affinity and specificity to macromolecular targets. To date, the highest affinity (10)Fn3 variants have been selected by mRNA display of libraries generated by randomizing all three complementarity-determining region -like loops of the (10)Fn3 scaffold. The sub-nanomolar affinities of such antibody mimics have been attributed to the extremely large size of the library accessible by mRNA display (10(12) unique sequences). Here we describe the selection and affinity maturation of (10)Fn3-based antibody mimics with dissociation constants as low as 350 pM selected from significantly smaller libraries (10(7)-10(9) different sequences), which were constructed by randomizing only 14 (10)Fn3 residues. The finding that two adjacent loops in human (10)Fn3 provide a large enough variable surface area to select high-affinity antibody mimics is significant because a smaller deviation from wild-type (10)Fn3 sequence is associated with a higher stability of selected antibody mimics. Our results also demonstrate the utility of an affinity-maturation strategy that led to a 340-fold improvement in affinity by maximizing sampling of sequence space close to the original selected antibody mimic. A striking feature of the highest affinity antibody mimics selected against lysozyme is a pair of cysteines on adjacent loops, in positions 28 and 77, which are critical for the affinity of the (10)Fn3 variant for its target and are close enough to form a disulfide bond. The selection of this cysteine pair is structurally analogous to the natural evolution of disulfide bonds found in new antigen receptors of cartilaginous fish and in camelid heavy-chain variable domains. We propose that future library designs incorporating such an interloop disulfide will further facilitate the selection of high-affinity, highly stable antibody mimics from

  16. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2011-02-15

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  17. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    International Nuclear Information System (INIS)

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2±1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a 111In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  18. Long Maturity Forward Rates

    DEFF Research Database (Denmark)

    Christiansen, Charlotte

    2001-01-01

    The paper aims to improve the knowledge of the empirical properties of the long maturity region of the forward rate curve. Firstly, the theoretical negative correlation between the slope at the long end of the forward rate curve and the term structure variance is recovered empirically and found to...... be statistically significant. Secondly, the expectations hypothesis is analyzed for the long maturity region of the forward rate curve using "forward rate" regressions. The expectations hypothesis is numerically close to being accepted but is statistically rejected. The findings provide mixed support...

  19. Asymptotics of implied volatility far from maturity

    OpenAIRE

    Michael R., Tehranchi

    2009-01-01

    This note explores the behaviour of the implied volatility of a European call option far from maturity. Asymptotic formulae are derived with precise control over the error terms. The connection between the asymptotic implied volatility and the cumulant generating function of the logarithm of the underlying stock price is discussed in detail and illustrated by examples.

  20. Enuresis: A maturational lag

    OpenAIRE

    Cary, Paul

    2003-01-01

    Enuresis is not a disease, but a disorder caused by delays in the maturation of three physiological processes: persistence of spontaneous bladder contractions, bladder volume exceeding the nocturnal functional bladder capacity and persistence of elevated sleep/arousal thresholds. Enuresis has been subtyped into two different groups, depending on whether the predominant feature is frequent small voidings (excessive bladder contractions) or large urinary volume (volume-dependent). The clinical ...

  1. Audit Maturity Model

    OpenAIRE

    Bhattacharya Uttam; Rahut Amit Kumar; De Sujoy

    2014-01-01

    Today it is crucial for organizations to pay even greater attention on quality management as the importance of this function in achieving ultimate business objectives is increasingly becoming clearer. Importance of the Quality Management Function in achieving basic need by ensuring compliance with Capability Maturity Model Integrated or International Organization for Standardization is a basic demand from business nowadays. However, Quality Management Function and its processes need to be mad...

  2. Mechanisms of lipase maturation

    OpenAIRE

    Doolittle, Mark H.; Péterfy, Miklós

    2010-01-01

    Lipases are acyl hydrolases that represent a diverse group of enzymes present in organisms ranging from prokaryotes to humans. This article focuses on an evolutionarily related family of extracellular lipases that include lipoprotein lipase, hepatic lipase and endothelial lipase. As newly synthesized proteins, these lipases undergo a series of co- and post-translational maturation steps occurring in the endoplasmic reticulum, including glycosylation and glycan processing, and protein folding ...

  3. The maturity of Nuclear Law

    International Nuclear Information System (INIS)

    The ever-increasing use of atomic energy since 1950 has generated a set of rules called for practical reasons Nuclear Law. This branch of law covers a wide scope of related activities and, specialized studies have apparently foreseen all conceivable hypotheses. The international character of Nuclear Law explains the basic harmony of international legislation. The methods of comparative Law and International Private Law as well as the joint, indepth work of scientists and jurists will bring about steady progress towards legislative unity and prompt solution to conflicts. The expectable revitalization of nuclear-electric programs early in the 21st. century will give rise to a Nuclear juridical community which can already be perceived through the maturity Nuclear Law has reached. (Author)

  4. The classical origin of quantum affine algebra in squashed sigma models

    OpenAIRE

    Kawaguchi, Io; Matsumoto, Takuya; Yoshida, Kentaroh

    2012-01-01

    We consider a quantum affine algebra realized in two-dimensional non-linear sigma models with target space three-dimensional squashed sphere. Its affine generators are explicitly constructed and the Poisson brackets are computed. The defining relations of quantum affine algebra in the sense of the Drinfeld first realization are satisfied at classical level. The relation to the Drinfeld second realization is also discussed including higher conserved charges. Finally we comment on a semiclassic...

  5. Maturity effects in energy futures

    Energy Technology Data Exchange (ETDEWEB)

    Serletis, Apostolos (Calgary Univ., AB (CA). Dept. of Economics)

    1992-04-01

    This paper examines the effects of maturity on future price volatility and trading volume for 129 energy futures contracts recently traded in the NYMEX. The results provide support for the maturity effect hypothesis, that is, energy futures prices to become more volatile and trading volume increases as futures contracts approach maturity. (author).

  6. Affine density in wavelet analysis

    CERN Document Server

    Kutyniok, Gitta

    2007-01-01

    In wavelet analysis, irregular wavelet frames have recently come to the forefront of current research due to questions concerning the robustness and stability of wavelet algorithms. A major difficulty in the study of these systems is the highly sensitive interplay between geometric properties of a sequence of time-scale indices and frame properties of the associated wavelet systems. This volume provides the first thorough and comprehensive treatment of irregular wavelet frames by introducing and employing a new notion of affine density as a highly effective tool for examining the geometry of sequences of time-scale indices. Many of the results are new and published for the first time. Topics include: qualitative and quantitative density conditions for existence of irregular wavelet frames, non-existence of irregular co-affine frames, the Nyquist phenomenon for wavelet systems, and approximation properties of irregular wavelet frames.

  7. Protein isolation using affinity chromatography

    OpenAIRE

    Besselink, T.

    2012-01-01

    Many product or even waste streams in the food industry contain components that may have potential for e.g. functional foods. These streams are typically large in volume and the components of interest are only present at low concentrations. A robust and highly selective separation process should be developed for efficient isolation of the components. Affinity chromatography is such a selective method. Ligands immobilized to a stationary phase (e.g., a resin or membrane) are used to bind the c...

  8. Inhomogeneous self-affine carpets

    OpenAIRE

    Fraser, Jonathan M.

    2013-01-01

    We investigate the dimension theory of inhomogeneous self-affine carpets. Through the work of Olsen, Snigireva and Fraser, the dimension theory of inhomogeneous self-similar sets is now relatively well-understood, however, almost no progress has been made concerning more general non-conformal inhomogeneous attractors. If a dimension is countably stable, then the results are immediate and so we focus on the upper and lower box dimensions and compute these explicitly for large classes of inhomo...

  9. Stationary fuel cell systems. Danish strategy for maturing micro- combined power and heat generation for the market. To make the house owners environmentally conscious prosumers; Stationaere braendselscellesystemer. Dansk plan for markedsmodning af mikrokraftvarme. Goer boligejerne til miljoevenlige prosumenter

    Energy Technology Data Exchange (ETDEWEB)

    2011-04-15

    The aim of this new market maturing plan is to show how innovative technologies for micro stationary fuel cell cogeneration systems can enter both the Danish and the international markets. The report first presents a general description of all types of stationary plants. Not all of them are yet ready for commercialization - some are still in the research and development phase. The plan documents that there is a need for incentives for maturing the technologies for the market after the demonstration phase, and it presents methods for market introduction in Denmark and internationally. (ln)

  10. Alternative affinity tools: more attractive than antibodies?

    NARCIS (Netherlands)

    Ruigrok, V.J.B.; Levisson, M.; Eppink, M.H.M.; Smidt, H.; Oost, van der J.

    2011-01-01

    Antibodies are the most successful affinity tools used today, in both fundamental and applied research (diagnostics, purification and therapeutics). Nonetheless, antibodies do have their limitations, including high production costs and low stability. Alternative affinity tools based on nucleic acids

  11. Mature Cystic Renal Teratoma

    OpenAIRE

    Yavuz, Alpaslan; Ceken, Kagan; Alimoglu, Emel; Bahar AKKAYA

    2014-01-01

    Teratomas are rare germline tumors that originate from one or more embryonic germ cell layers. Teratoma of the kidney is extremely rare, and less than 30 cases of primary intrarenal teratomas have been published to date. We report the main radiologic features of an unusual case of mature cystic teratoma arising from the left kidney in a two-year-old boy. A left-sided abdominal mass was detected on physical examination and B-Mod Ultrasound (US) examination revealed a heterogeneous mass with ce...

  12. Spectral affinity in protein networks

    Directory of Open Access Journals (Sweden)

    Teng Shang-Hua

    2009-11-01

    Full Text Available Abstract Background Protein-protein interaction (PPI networks enable us to better understand the functional organization of the proteome. We can learn a lot about a particular protein by querying its neighborhood in a PPI network to find proteins with similar function. A spectral approach that considers random walks between nodes of interest is particularly useful in evaluating closeness in PPI networks. Spectral measures of closeness are more robust to noise in the data and are more precise than simpler methods based on edge density and shortest path length. Results We develop a novel affinity measure for pairs of proteins in PPI networks, which uses personalized PageRank, a random walk based method used in context-sensitive search on the Web. Our measure of closeness, which we call PageRank Affinity, is proportional to the number of times the smaller-degree protein is visited in a random walk that restarts at the larger-degree protein. PageRank considers paths of all lengths in a network, therefore PageRank Affinity is a precise measure that is robust to noise in the data. PageRank Affinity is also provably related to cluster co-membership, making it a meaningful measure. In our experiments on protein networks we find that our measure is better at predicting co-complex membership and finding functionally related proteins than other commonly used measures of closeness. Moreover, our experiments indicate that PageRank Affinity is very resilient to noise in the network. In addition, based on our method we build a tool that quickly finds nodes closest to a queried protein in any protein network, and easily scales to much larger biological networks. Conclusion We define a meaningful way to assess the closeness of two proteins in a PPI network, and show that our closeness measure is more biologically significant than other commonly used methods. We also develop a tool, accessible at http://xialab.bu.edu/resources/pnns, that allows the user to

  13. Manifolds with integrable affine shape operator

    Directory of Open Access Journals (Sweden)

    Daniel A. Joaquín

    2005-05-01

    Full Text Available This work establishes the conditions for the existence of vector fields with the property that theirs covariant derivative, with respect to the affine normal connection, be the affine shape operatorS in hypersurfaces. Some results are obtained from this property and, in particular, for some kind of affine decomposable hypersurfaces we explicitely get the actual vector fields.

  14. Assessment of Solvated Interaction Energy Function for Ranking Antibody-Antigen Binding Affinities.

    Science.gov (United States)

    Sulea, Traian; Vivcharuk, Victor; Corbeil, Christopher R; Deprez, Christophe; Purisima, Enrico O

    2016-07-25

    Affinity modulation of antibodies and antibody fragments of therapeutic value is often required in order to improve their clinical efficacies. Virtual affinity maturation has the potential to quickly focus on the critical hotspot residues without the combinatorial explosion problem of conventional display and library approaches. However, this requires a binding affinity scoring function that is capable of ranking single-point mutations of a starting antibody. We focus here on assessing the solvated interaction energy (SIE) function that was originally developed for and is widely applied to scoring of protein-ligand binding affinities. To this end, we assembled a structure-function data set called Single-Point Mutant Antibody Binding (SiPMAB) comprising several antibody-antigen systems suitable for this assessment, i.e., based on high-resolution crystal structures for the parent antibodies and coupled with high-quality binding affinity measurements for sets of single-point antibody mutants in each system. Using this data set, we tested the SIE function with several mutation protocols based on the popular methods SCWRL, Rosetta, and FoldX. We found that the SIE function coupled with a protocol limited to sampling only the mutated side chain can reasonably predict relative binding affinities with a Spearman rank-order correlation coefficient of about 0.6, outperforming more aggressive sampling protocols. Importantly, this performance is maintained for each of the seven system-specific component subsets as well as for other relevant subsets including non-alanine and charge-altering mutations. The transferability and enrichment in affinity-improving mutants can be further enhanced using consensus ranking over multiple methods, including the SIE, Talaris, and FOLDEF energy functions. The knowledge gained from this study can lead to successful prospective applications of virtual affinity maturation. PMID:27367467

  15. The application of magnetic force differentiation for the measurement of the affinity of peptide libraries

    International Nuclear Information System (INIS)

    A new method has been developed for measuring the binding affinity of phage displayed peptides and a target protein using magnetic particles. The specific interaction between the phage displayed peptides and the target protein was subject to a force generated by the magnetic particle. The binding affinity was obtained by analyzing the force-bond lifetime

  16. Mature Cystic Renal Teratoma

    International Nuclear Information System (INIS)

    Teratomas are rare germline tumors that originate from one or more embryonic germ cell layers. Teratoma of the kidney is extremely rare, and less than 30 cases of primary intrarenal teratomas have been published to date. We report the main radiologic features of an unusual case of mature cystic teratoma arising from the left kidney in a two-year-old boy. A left-sided abdominal mass was detected on physical examination and B-Mod Ultrasound (US) examination revealed a heterogeneous mass with central cystic component. Computed tomography (CT) demonstrated a lobulated, heterogeneous, hypodense mass extending craniocaudally from the splenic hilum to the level of the left iliac fossa. Nephrectomy was performed and a large, fatty mass arising from the left kidney was excised. The final pathologic diagnosis was confirmed as cystic renal teratoma

  17. Rational self-affine tiles

    CERN Document Server

    Steiner, Wolfgang

    2012-01-01

    An integral self-affine tile is the solution of a set equation $\\mathbf{A} \\mathcal{T} = \\bigcup_{d \\in \\mathcal{D}} (\\mathcal{T} + d)$, where $\\mathbf{A}$ is an $n \\times n$ integer matrix and $\\mathcal{D}$ is a finite subset of $\\mathbb{Z}^n$. In the recent decades, these objects and the induced tilings have been studied systematically. We extend this theory to matrices $\\mathbf{A} \\in \\mathbb{Q}^{n \\times n}$. We define rational self-affine tiles as compact subsets of the open subring $\\mathbb{R}^n\\times \\prod_\\mathfrak{p} K_\\mathfrak{p}$ of the ad\\'ele ring $\\mathbb{A}_K$, where the factors of the (finite) product are certain $\\mathfrak{p}$-adic completions of a number field $K$ that is defined in terms of the characteristic polynomial of $\\mathbf{A}$. Employing methods from classical algebraic number theory, Fourier analysis in number fields, and results on zero sets of transfer operators, we establish a general tiling theorem for these tiles. We also associate a second kind of tiles with a rational matr...

  18. The affine quantum gravity programme

    International Nuclear Information System (INIS)

    The central principle of affine quantum gravity is securing and maintaining the strict positivity of the matrix { g-hat ab(x)} composed of the spatial components of the local metric operator. On spectral grounds, canonical commutation relations are incompatible with this principle, and they must be replaced by noncanonical, affine commutation relations. Due to the partial second-class nature of the quantum gravitational constraints, it is advantageous to use the recently developed projection operator method, which treats all quantum constraints on an equal footing. Using this method, enforcement of regularized versions of the gravitational operator constraints is formulated quite naturally by means of a novel and relatively well-defined functional integral involving only the same set of variables that appears in the usual classical formulation. It is anticipated that skills and insight to study this formulation can be developed by studying special, reduced-variable models that still retain some basic characteristics of gravity, specifically a partial second-class constraint operator structure. Although perturbatively nonrenormalizable, gravity may possibly be understood nonperturbatively from a hard-core perspective that has proved valuable for specialized models. Finally, developing a procedure to pass to the genuine physical Hilbert space involves several interconnected steps that require careful coordination

  19. Maturational and Non-Maturational Factors in Heritage Language Acquisition

    Science.gov (United States)

    Moon, Ji Hye

    2012-01-01

    This dissertation aims to understand the maturational and non-maturational aspects of early bilingualism and language attrition in heritage speakers who have acquired their L1 incompletely in childhood. The study highlights the influential role of age and input dynamics in early L1 development, where the timing of reduction in L1 input and the…

  20. Role of adenosine in oligodendrocyte precursor maturation

    Directory of Open Access Journals (Sweden)

    Elisabetta Coppi

    2015-04-01

    Full Text Available Differentiation and maturation of oligodendroglial cells are postnatal processes involving specific morphological changes correlated with the expression of stage-specific surface antigens and functional voltage-gated ion channels. A small fraction of oligodendrocyte progenitor cells (OPCs generated during development are maintained in an immature and slowly proliferative or quiescent state in the adult central nervous system (CNS representing an endogenous reservoir of immature cells. Adenosine receptors are expressed by OPCs and a key role of adenosine in oligodendrocyte maturation has been recently recognised. As evaluated on OPC cultures, adenosine by stimulating A1 receptors, promotes oligodendrocyte maturation and inhibits their proliferation; on the contrary by stimulating A2A receptors, it inhibits oligodendrocyte maturation. A1 and A2A receptor-mediated effects are related to opposite modifications of outward delayed rectifying membrane K+ currents (IK that are involved in regulation of oligodendrocyte differentiation. Brain A1 and A2A receptors might represent new molecular targets for drugs useful in demyelinating pathologies, such as multiple sclerosis (MS, stroke and brain trauma.

  1. Large deviations and stochastic volatility with jumps: asymptotic implied volatility for affine models

    OpenAIRE

    Antoine Jacquier; Martin Keller-Ressel; Aleksandar Mijatovic

    2011-01-01

    Let $\\sigma_t(x)$ denote the implied volatility at maturity $t$ for a strike $K=S_0 e^{xt}$, where $x\\in\\bbR$ and $S_0$ is the current value of the underlying. We show that $\\sigma_t(x)$ has a uniform (in $x$) limit as maturity $t$ tends to infinity, given by the formula $\\sigma_\\infty(x)=\\sqrt{2}(h^*(x)^{1/2}+(h^*(x)-x)^{1/2})$, for $x$ in some compact neighbourhood of zero in the class of affine stochastic volatility models. The function $h^*$ is the convex dual of the limiting cumulant gen...

  2. Conformal field theory on affine Lie groups

    International Nuclear Information System (INIS)

    Working directly on affine Lie groups, we construct several new formulations of the WZW model, the gauged WZW model, and the generic affine-Virasoro action. In one formulation each of these conformal field theories (CFTs) is expressed as a one-dimensional mechanical system whose variables are coordinates on the affine Lie group. When written in terms of the affine group element, this formulation exhibits a two-dimensional WZW term. In another formulation each CFT is written as a two-dimensional field theory, with a three- dimensional WZW term, whose fields are coordinates on the affine group. On the basis of these equivalent formulations, we develop a translation dictionary in which the new formulations on the affine Lie group are understood as mode formulations of the conventional formulations on the Lie group. Using this dictionary, we also express each CFT as a three-dimensional field theory on the Lie group with a four-dimensional WZW term. 36 refs

  3. Conformal field theory on affine Lie groups

    Energy Technology Data Exchange (ETDEWEB)

    Clubok, K.S.

    1996-04-01

    Working directly on affine Lie groups, we construct several new formulations of the WZW model, the gauged WZW model, and the generic affine-Virasoro action. In one formulation each of these conformal field theories (CFTs) is expressed as a one-dimensional mechanical system whose variables are coordinates on the affine Lie group. When written in terms of the affine group element, this formulation exhibits a two-dimensional WZW term. In another formulation each CFT is written as a two-dimensional field theory, with a three- dimensional WZW term, whose fields are coordinates on the affine group. On the basis of these equivalent formulations, we develop a translation dictionary in which the new formulations on the affine Lie group are understood as mode formulations of the conventional formulations on the Lie group. Using this dictionary, we also express each CFT as a three-dimensional field theory on the Lie group with a four-dimensional WZW term. 36 refs.

  4. Maximin affinity learning of image segmentation

    CERN Document Server

    Turaga, Srinivas C; Helmstaedter, Moritz; Denk, Winfried; Seung, H Sebastian

    2009-01-01

    Images can be segmented by first using a classifier to predict an affinity graph that reflects the degree to which image pixels must be grouped together and then partitioning the graph to yield a segmentation. Machine learning has been applied to the affinity classifier to produce affinity graphs that are good in the sense of minimizing edge misclassification rates. However, this error measure is only indirectly related to the quality of segmentations produced by ultimately partitioning the affinity graph. We present the first machine learning algorithm for training a classifier to produce affinity graphs that are good in the sense of producing segmentations that directly minimize the Rand index, a well known segmentation performance measure. The Rand index measures segmentation performance by quantifying the classification of the connectivity of image pixel pairs after segmentation. By using the simple graph partitioning algorithm of finding the connected components of the thresholded affinity graph, we are ...

  5. Career Maturity of Welfare Recipients.

    Science.gov (United States)

    Beckman, Carol M.

    To investigate the career maturity of welfare recipients, this thesis examines six independent variables: (1) race; (2) sex; (3) age; (4) level of formal education; (5) general intelligence; and (6) locus of control. Scales taken from the Career Maturity Inventory served as the dependent variables. The sample consisted of 83 welfare recipients who…

  6. Methods for Improving Aptamer Binding Affinity

    OpenAIRE

    Hijiri Hasegawa; Nasa Savory; Koichi Abe; Kazunori Ikebukuro

    2016-01-01

    Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamers is required to achieve desired binding affinities. The optimization of primary sequences and stabilization of aptamer conformations are the main approaches to refining the binding properties of a...

  7. Covariant Functional Calculi from the Affine Groups

    OpenAIRE

    Gong, Yafang

    2009-01-01

    Invoking the Clifford-Hermite Wavelets from Clifford analysis, we use the covariances of affine groups to construct a kind of functional calculi for several non-commuting bounded operators. Functional calculi are the intertwining transforms between the representations of affine groups in the space $L^2(\\mathbb R^m)$ and in the space of bounded operators. It turns out that the Weyl calculus is the value of this new functional calculus at the identity of affine groups. Our app...

  8. Multipole solutions in metric-affine gravity

    CERN Document Server

    Socorro, J; Macías, A; Mielke, E W; Socorro, José; Lämmerzahl, Claus; Macías, Alfredo; Mielke, Eckehard W.

    1998-01-01

    Above Planck energies, the spacetime might become non--Riemannian, as it is known fron string theory and inflation. Then geometries arise in which nonmetricity and torsion appear as field strengths, side by side with curvature. By gauging the affine group, a metric affine gauge theory emerges as dynamical framework. Here, by using the harmonic map ansatz, a new class of multipole like solutions in the metric affine gravity theory (MAG) is obtained.

  9. Maximin affinity learning of image segmentation

    OpenAIRE

    Srinivas C Turaga; Briggman, Kevin L; Helmstaedter, Moritz; Denk, Winfried; Seung, H. Sebastian

    2009-01-01

    Images can be segmented by first using a classifier to predict an affinity graph that reflects the degree to which image pixels must be grouped together and then partitioning the graph to yield a segmentation. Machine learning has been applied to the affinity classifier to produce affinity graphs that are good in the sense of minimizing edge misclassification rates. However, this error measure is only indirectly related to the quality of segmentations produced by ultimately partitioning the a...

  10. Discrete Affine Minimal Surfaces with Indefinite Metric

    OpenAIRE

    Craizer, Marcos; Anciaux, Henri; Lewiner, Thomas

    2008-01-01

    Inspired by the Weierstrass representation of smooth affine minimal surfaces with indefinite metric, we propose a constructive process producing a large class of discrete surfaces that we call discrete affine minimal surfaces. We show that they are critical points of an affine area functional defined on the space of quadrangular discrete surfaces. The construction makes use of asymptotic coordinates and allows defining the discrete analogs of some differential geometric objects, such as the n...

  11. Creating customer value and the use of the product life cycle to generate strategic options for maturing low-cost service-retail markets -A case study on The Spirit Group value pub food retail concept"Two for One"

    OpenAIRE

    Twaites, Claire

    2007-01-01

    This is a case study on a low-cost service retail concept known as "Two for One" a pub-food chain owned by The Spirit Group. The thesis aims to explore the nature and characteristics of the product life cycle for low-cost service retailers with the objective to establish strategic options. The nature of low-cost propositions is that price is the main strategic driver to compete for growth and market share. However in maturing markets where competition is high and margins are low, retailers...

  12. A Novel Vertex Affinity for Community Detection

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Andy [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sanders, Geoffrey [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Henson, Van [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vassilevski, Panayot [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-10-05

    We propose a novel vertex affinity measure in this paper. The new vertex affinity quantifies the proximity between two vertices in terms of their clustering strength and is ideal for such graph analytics applications as community detection. We also developed a framework that combines simple graph searches and resistance circuit formulas to compute the vertex affinity efficiently. We study the properties of the new affinity measure empirically in comparison to those of other popular vertex proximity metrics. Our results show that the existing metrics are ill-suited for community detection due to their lack of fundamental properties that are essential for correctly capturing inter- and intra-cluster vertex proximity.

  13. Compact noncontraction semigroups of affine operators

    Science.gov (United States)

    Voynov, A. S.; Protasov, V. Yu

    2015-07-01

    We analyze compact multiplicative semigroups of affine operators acting in a finite-dimensional space. The main result states that every such semigroup is either contracting, that is, contains elements of arbitrarily small operator norm, or all its operators share a common invariant affine subspace on which this semigroup is contracting. The proof uses functional difference equations with contraction of the argument. We look at applications to self-affine partitions of convex sets, the investigation of finite affine semigroups and the proof of a criterion of primitivity for nonnegative matrix families. Bibliography: 32 titles.

  14. Protein Complex Purification by Affinity Capture.

    Science.gov (United States)

    LaCava, John; Fernandez-Martinez, Javier; Hakhverdyan, Zhanna; Rout, Michael P

    2016-01-01

    Affinity capture has become a powerful technique for consistently purifying endogenous protein complexes, facilitating biochemical and biophysical assays on otherwise inaccessible biological assemblies, and enabling broader interactomic exploration. For this procedure, cells are broken and their contents separated and extracted into a solvent, permitting access to target macromolecular complexes thus released in solution. The complexes are specifically enriched from the extract onto a solid medium coupled with an affinity reagent-usually an antibody-that recognizes the target either directly or through an appended affinity tag, allowing subsequent characterization of the complex. Here, we discuss approaches and considerations for purifying endogenous yeast protein complexes by affinity capture. PMID:27371601

  15. Structural determinants of sigma receptor affinity

    International Nuclear Information System (INIS)

    The structural determinants of sigma receptor affinity have been evaluated by examining a wide range of compounds related to opioids, neuroleptics, and phenylpiperidine dopaminergic structures for affinity at sigma receptor-binding sites labeled with (+)-[3H]3-PPP. Among opioid compounds, requirements for sigma receptor affinity differ strikingly from the determinants of affinity for conventional opiate receptors. Sigma sites display reverse stereoselectivity to classical opiate receptors. Multi-ringed opiate-related compounds such as morphine and naloxone have negligible affinity for sigma sites, with the highest sigma receptor affinity apparent for benzomorphans which lack the C ring of opioids. Highest affinity among opioids and other compounds occurs with more lipophilic N-substituents. This feature is particularly striking among the 3-PPP derivatives as well as the opioids. The butyrophenone haloperidol is the most potent drug at sigma receptors we have detected. Among the series of butyrophenones, receptor affinity is primarily associated with the 4-phenylpiperidine moiety. Conformational calculations for various compounds indicate a fairly wide range of tolerance for distances between the aromatic ring and the amine nitrogen, which may account for the potency at sigma receptors of structures of considerable diversity. Among the wide range of structures that bind to sigma receptor-binding sites, the common pharmacophore associated with high receptor affinity is a phenylpiperidine with a lipophilic N-substituent

  16. Structural determinants of sigma receptor affinity

    Energy Technology Data Exchange (ETDEWEB)

    Largent, B.L.; Wikstroem, H.G.; Gundlach, A.L.; Snyder, S.H.

    1987-12-01

    The structural determinants of sigma receptor affinity have been evaluated by examining a wide range of compounds related to opioids, neuroleptics, and phenylpiperidine dopaminergic structures for affinity at sigma receptor-binding sites labeled with (+)-(/sup 3/H)3-PPP. Among opioid compounds, requirements for sigma receptor affinity differ strikingly from the determinants of affinity for conventional opiate receptors. Sigma sites display reverse stereoselectivity to classical opiate receptors. Multi-ringed opiate-related compounds such as morphine and naloxone have negligible affinity for sigma sites, with the highest sigma receptor affinity apparent for benzomorphans which lack the C ring of opioids. Highest affinity among opioids and other compounds occurs with more lipophilic N-substituents. This feature is particularly striking among the 3-PPP derivatives as well as the opioids. The butyrophenone haloperidol is the most potent drug at sigma receptors we have detected. Among the series of butyrophenones, receptor affinity is primarily associated with the 4-phenylpiperidine moiety. Conformational calculations for various compounds indicate a fairly wide range of tolerance for distances between the aromatic ring and the amine nitrogen, which may account for the potency at sigma receptors of structures of considerable diversity. Among the wide range of structures that bind to sigma receptor-binding sites, the common pharmacophore associated with high receptor affinity is a phenylpiperidine with a lipophilic N-substituent.

  17. The affine theory of gravitation and electromagnetism I

    CERN Document Server

    Poplawski, N J

    2006-01-01

    The affine variational principle of Eddington generates the Einstein field equations of general relativity in vacuum with a non-zero cosmological constant. We generalize this principle to include electromagnetism, obtaining the Einstein--Maxwell field equations and the Lorentz equation of motion. We vary the action with respect to the quantities that appear in the definition of the electromagnetic covariant derivative: the affine (nonsymmetric) connection and the electromagnetic potential, while the Lagrangian density is taken to be the square root of the determinant of a linear combination of the symmetrized Ricci tensor and the electromagnetic field tensor. This construction generates a symmetric metric tensor and a connection with torsion that depends only on the torsion vector. The whole formulation is valid only for very weak electromagnetic fields on the order of the magnetic field in interstellar space.

  18. Maturation of Shark Single-Domain (IgNAR) Antibodies: Evidence for Induced-Fit Binding

    Energy Technology Data Exchange (ETDEWEB)

    Stanfield, R.L.; Dooley, H.; Verdino, P.; Flajnik, M.F.; Wilson, I.A.; /Scripps Res. Inst. /Maryland U.

    2007-07-13

    Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts with antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.

  19. Term premia and interest rate forecasts in affine models

    OpenAIRE

    Duffee, Gregory R.

    2000-01-01

    I find that the standard class of affine models produces poor forecasts of future changes in Treasury yields. Better forecasts are generated by assuming that yields follow random walks. The failure of these models is driven by one of their key features: the compensation that investors receive for facing risk is a multiple of the variance of the risk. This means that risk compensation cannot vary independently of interest rate volatility. I also describe and empirically estimate a class of mod...

  20. Control of autoantibody affinity by selection against amino acid replacements in the complementarity-determining regions.

    OpenAIRE

    Børretzen, M; Randen, I; Zdárský, E; Førre, O; Natvig, J B; Thompson, K M

    1994-01-01

    Rheumatoid factor (RF) autoantibodies can be produced in healthy individuals after infections or immunizations and thus escape normal tolerization mechanisms. It has not been clear whether such autoantibodies can undergo somatic hypermutation and affinity maturation similar to antibodies to exogenous antigens. We have investigated how these autoantibodies are regulated in normal individuals by analyzing the sequences of monoclonal IgM RFs obtained as hybridomas from donors after immunization....

  1. BUSINESS PROCESS MANAGEMENT MATURITY MODEL - SERBIAN ENTERPRISES' MATURITY LEVEL

    OpenAIRE

    Marija Anđelković Pešić; Vesna Janković Milić; Aleksandra Anđelković

    2012-01-01

    Business process management maturity model enables description of "as-is" enterprise's state, in terms of presence and acceptance of process approach.The heart of this model includes five factors or levers, critical for successful implementation of business process management. These factors are: strategic approach, process management, technology, employee management, and business culture. The above-mentioned factors influence the level of enterprise's maturity. At each level, an enterprise is...

  2. Scaling analysis of affinity propagation.

    Science.gov (United States)

    Furtlehner, Cyril; Sebag, Michèle; Zhang, Xiangliang

    2010-06-01

    We analyze and exploit some scaling properties of the affinity propagation (AP) clustering algorithm proposed by Frey and Dueck [Science 315, 972 (2007)]. Following a divide and conquer strategy we setup an exact renormalization-based approach to address the question of clustering consistency, in particular, how many cluster are present in a given data set. We first observe that the divide and conquer strategy, used on a large data set hierarchically reduces the complexity O(N2) to O(N((h+2)/(h+1))) , for a data set of size N and a depth h of the hierarchical strategy. For a data set embedded in a d -dimensional space, we show that this is obtained without notably damaging the precision except in dimension d=2 . In fact, for d larger than 2 the relative loss in precision scales such as N((2-d)/(h+1)d). Finally, under some conditions we observe that there is a value s* of the penalty coefficient, a free parameter used to fix the number of clusters, which separates a fragmentation phase (for ss*) of the underlying hidden cluster structure. At this precise point holds a self-similarity property which can be exploited by the hierarchical strategy to actually locate its position, as a result of an exact decimation procedure. From this observation, a strategy based on AP can be defined to find out how many clusters are present in a given data set. PMID:20866473

  3. Free C+ actions on affine threefolds

    OpenAIRE

    Kraft, H.

    2005-01-01

    We study algebraic actions of the additive group C+ on an affine threefold X and prove a smoothness property for the quotient morphism X -< X//C+. Then, following Shulim Kaliman, we give a proof of the conjecture that every free C+ action on affine 3-space C^3 is a translation.

  4. Lectures on extended affine Lie algebras

    CERN Document Server

    Neher, Erhard

    2010-01-01

    We give an introduction to the structure theory of extended affine Lie algebras, which provide a common framework for finite-dimensional semisimple, affine and toroidal Lie algebras. The notes are based on a lecture series given during the Fields Institute summer school at the University of Ottawa in June 2009.

  5. Affine Constellations Without Mutually Unbiased Counterparts

    CERN Document Server

    Weigert, Stefan

    2010-01-01

    It has been conjectured that a complete set of mutually unbiased bases in a space of dimension d exists if and only if there is an affine plane of order d. We introduce affine constellations and compare their existence properties with those of mutually unbiased constellations, mostly in dimension six. The observed discrepancies make a deeper relation between the two existence problems unlikely.

  6. Affine constellations without mutually unbiased counterparts

    Energy Technology Data Exchange (ETDEWEB)

    Weigert, Stefan [Department of Mathematics, University of York, York YO10 5DD (United Kingdom); Durt, Thomas, E-mail: slow500@york.ac.u, E-mail: thomdurt@vub.ac.b [IR-TONA, VUB, BE-1050 Brussels (Belgium)

    2010-10-08

    It has been conjectured that a complete set of mutually unbiased bases in a space of dimension d exists if and only if there is an affine plane of order d. We introduce affine constellations and compare their existence properties with those of mutually unbiased constellations. The observed discrepancies make a deeper relation between the two existence problems unlikely. (fast track communication)

  7. Dyes with high affinity for polylactide

    Institute of Scientific and Technical Information of China (English)

    Liang He; Shu Fen Zhang; Bing Tao Tang; Li Li Wang; Jin Zong Yang

    2007-01-01

    Attempts were made to develop dyes with high affinity for polylactide as an alternative to the existent commercial disperse dyes.The dyes synthesized according to the affinity concept of dye to polylactide exhibited excellent dyeing properties on polylactide compared with the commercial disperse dyes.

  8. Porosity of Self-affine Sets

    Institute of Scientific and Technical Information of China (English)

    Lifeng XI

    2008-01-01

    In this paper,it is proved that any self-affine set satisfying the strong separation condition is uniformly porous.The author constructs a self-affine set which is not porous,although the open set condition holds.Besides,the author also gives a C1 iterated function system such that its invariant set is not porous.

  9. Affine constellations without mutually unbiased counterparts

    International Nuclear Information System (INIS)

    It has been conjectured that a complete set of mutually unbiased bases in a space of dimension d exists if and only if there is an affine plane of order d. We introduce affine constellations and compare their existence properties with those of mutually unbiased constellations. The observed discrepancies make a deeper relation between the two existence problems unlikely. (fast track communication)

  10. Improving image segmentation by learning region affinities

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Lakshman [Los Alamos National Laboratory; Yang, Xingwei [TEMPLE UNIV.; Latecki, Longin J [TEMPLE UNIV.

    2010-11-03

    We utilize the context information of other regions in hierarchical image segmentation to learn new regions affinities. It is well known that a single choice of quantization of an image space is highly unlikely to be a common optimal quantization level for all categories. Each level of quantization has its own benefits. Therefore, we utilize the hierarchical information among different quantizations as well as spatial proximity of their regions. The proposed affinity learning takes into account higher order relations among image regions, both local and long range relations, making it robust to instabilities and errors of the original, pairwise region affinities. Once the learnt affinities are obtained, we use a standard image segmentation algorithm to get the final segmentation. Moreover, the learnt affinities can be naturally unutilized in interactive segmentation. Experimental results on Berkeley Segmentation Dataset and MSRC Object Recognition Dataset are comparable and in some aspects better than the state-of-art methods.

  11. Solar Hydrogen Reaching Maturity

    Directory of Open Access Journals (Sweden)

    Rongé Jan

    2015-09-01

    Full Text Available Increasingly vast research efforts are devoted to the development of materials and processes for solar hydrogen production by light-driven dissociation of water into oxygen and hydrogen. Storage of solar energy in chemical bonds resolves the issues associated with the intermittent nature of sunlight, by decoupling energy generation and consumption. This paper investigates recent advances and prospects in solar hydrogen processes that are reaching market readiness. Future energy scenarios involving solar hydrogen are proposed and a case is made for systems producing hydrogen from water vapor present in air, supported by advanced modeling.

  12. Some Aspects of School Maturity

    OpenAIRE

    SATRAPOVÁ, Jana

    2008-01-01

    This bachelor{\\crq}s thesis is focused on the maturity of pre-school children for school work. Particularly it researches the level of children{\\crq}s knowledge in the period just before and immediately after entering school. The theoretical part of the thesis deals with pre-school characteristics, various aspects of school maturity and readiness for elementary school regarding the fact that in the period just before entering school and immediately after the beginning of school attendance cer...

  13. Algebraic (Volume) Density Property for Affine Homogeneous Spaces

    OpenAIRE

    Kaliman, Shulim; Kutzschebauch, Frank

    2015-01-01

    Let $X$ be a connected affine homogenous space of a linear algebraic group $G$ over $\\C$. (1) If $X$ is different from a line or a torus we show that the space of all algebraic vector fields on $X$ coincides with the Lie algebra generated by complete algebraic vector fields on $X$. (2) Suppose that $X$ has a $G$-invariant volume form $\\omega$. We prove that the space of all divergence-free (with respect to $\\omega$) algebraic vector fields on $X$ coincides with the Lie algebra generated by di...

  14. Tubular algebras and affine Kac-Moody algebras

    Institute of Scientific and Technical Information of China (English)

    Zheng-xin CHEN; Ya-nan LIN

    2007-01-01

    The purpose of this paper is to construct quotient algebras L(A)C1/I(A) of complex degenerate composition Lie algebras L(A)C1 by some ideals, where L(A)C1 is defined via Hall algebras of tubular algebras A, and to prove that the quotient algebras L(A)C1/I(A) are isomorphic to the corresponding affine Kac-Moody algebras. Moreover, it is shown that the Lie algebra Lre(A)C1 generated by A-modules with a real root coincides with the degenerate composition Lie algebra L(A)C1 generated by simple A-modules.

  15. Tubular algebras and affine Kac-Moody algebras

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The purpose of this paper is to construct quotient algebras L(A)1C/I(A) of complex degenerate composition Lie algebras L(A)1C by some ideals, where L(A)1C is defined via Hall algebras of tubular algebras A, and to prove that the quotient algebras L(A)1C/I(A) are isomorphic to the corresponding affine Kac-Moody algebras. Moreover, it is shown that the Lie algebra Lre(A)1C generated by A-modules with a real root coincides with the degenerate composition Lie algebra L(A)1C generated by simple A-modules.

  16. Structural insights into the affinity of Cel7A carbohydrate-binding module for lignin.

    Science.gov (United States)

    Strobel, Kathryn L; Pfeiffer, Katherine A; Blanch, Harvey W; Clark, Douglas S

    2015-09-11

    The high cost of hydrolytic enzymes impedes the commercial production of lignocellulosic biofuels. High enzyme loadings are required in part due to their non-productive adsorption to lignin, a major component of biomass. Despite numerous studies documenting cellulase adsorption to lignin, few attempts have been made to engineer enzymes to reduce lignin binding. In this work, we used alanine-scanning mutagenesis to elucidate the structural basis for the lignin affinity of Trichoderma reesei Cel7A carbohydrate binding module (CBM). T. reesei Cel7A CBM mutants were produced with a Talaromyces emersonii Cel7A catalytic domain and screened for their binding to cellulose and lignin. Mutation of aromatic and polar residues on the planar face of the CBM greatly decreased binding to both cellulose and lignin, supporting the hypothesis that the cellulose-binding face is also responsible for lignin affinity. Cellulose and lignin affinity of the 31 mutants were highly correlated, although several mutants displayed selective reductions in lignin or cellulose affinity. Four mutants with increased cellulose selectivity (Q2A, H4A, V18A, and P30A) did not exhibit improved hydrolysis of cellulose in the presence of lignin. Further reduction in lignin affinity while maintaining a high level of cellulose affinity is thus necessary to generate an enzyme with improved hydrolysis capability. This work provides insights into the structural underpinnings of lignin affinity, identifies residues amenable to mutation without compromising cellulose affinity, and informs engineering strategies for family one CBMs. PMID:26209638

  17. Maturity Control on the Patterns of Hydrocarbon Regeneration from Coal

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Rock-Eval pyrolysis and Py-GC experiments on naturally and artificially matured coal samples were carried out. The results suggest that both depolymerization and defuctionalization exist during the maturation and evolution of coal. The patterns of hydrocarbon regeneration are diverse at different stages of the maturation and evolution. When the vitrinite reflectance (R0) is 0.7%- 0.9%, bitumen is the richest in coal while activation energy is the minimum, and the temperature of peak yield is lower than that of primary hydrocarbon generation. However, if reflectance is greater than 0.9%, defunctionalization predominates and the temperature of peak regeneration is shown in lagging compared with the primary hydrocarbon generation. When reflectance is out of the "oil window", the peak temperature of hydrocarbon regeneration and that of the primary hydrocarbon generation seems to be continuous.

  18. Maturity Model of Software Product with Educational Maturity Model

    Directory of Open Access Journals (Sweden)

    R.Manjula

    2011-06-01

    Full Text Available Software product line engineering is an inter-disciplinary concept. It spans the dimensions of business, architecture, process,and the organization. Similarly, Education System engineering is also an inter-disciplinary concept, which spans the dimensions of academic, infrastructure, facilities, administration etc. Some of the potential benefits of this approach includecontinuous improvements in System quality and adhering to global standards. The increasing competency in IT and Educational Sectors necessitates a process maturity evaluation methodology. Accordingly, this paper presents an organizational maturity model for Education system for evaluating the maturity of multi- dimension factors and attributes of an Education System. Assessment questionnaires and a rating methodology comprise the framework of this Educational maturity model. The objective and design of the questionnaires are to collect information about the Education system engineering process from the multi perspectives of academic, infrastructure, administration, facilities etc. Furthermore, we conducted one case study and reported the assessment results using the organizational maturity model presented in this paper.

  19. Computational protein design suggests that human PCNA-partner interactions are not optimized for affinity.

    Science.gov (United States)

    Fridman, Yearit; Gur, Eyal; Fleishman, Sarel J; Aharoni, Amir

    2013-02-01

    Increasing the affinity of binding proteins is invaluable for basic and applied biological research. Currently, directed protein evolution experiments are the main approach for generating such proteins through the construction and screening of large mutant libraries. Proliferating cell nuclear antigen (PCNA) is an essential hub protein that interacts with many different partners to tightly regulate DNA replication and repair in all eukaryotes. Here, we used computational design to generate human PCNA mutants with enhanced affinity for several different partners. We identified double mutations in PCNA, outside the main partner binding site, that were predicted to increase PCNA-partner binding affinities compared to the wild-type protein by forming additional hydrophobic interactions with conserved residues in the PCNA partners. Affinity increases were experimentally validated with four different PCNA partners, demonstrating that computational design can reveal unexpected regions where affinity enhancements in natural systems are possible. The designed PCNA mutants can be used as a valuable tool for further examination of the regulation of PCNA-partner interactions during DNA replication and repair both in vitro and in vivo. More broadly, the ability to engineer affinity increases toward several PCNA partners suggests that interaction affinity is not an evolutionarily optimized trait of this system. PMID:23011891

  20. Evolution based on chromosome affinity from a network perspective

    Science.gov (United States)

    Monteiro, R. L. S.; Fontoura, J. R. A.; Carneiro, T. K. G.; Moret, M. A.; Pereira, H. B. B.

    2014-06-01

    Recent studies have focused on models to simulate the complex phenomenon of evolution of species. Several studies have been performed with theoretical models based on Darwin's theories to associate them with the actual evolution of species. However, none of the existing models include the affinity between individuals using network properties. In this paper, we present a new model based on the concept of affinity. The model is used to simulate the evolution of species in an ecosystem composed of individuals and their relationships. We propose an evolutive algorithm that incorporates the degree centrality and efficiency network properties to perform the crossover process and to obtain the network topology objective, respectively. Using a real network as a starting point, we simulate its evolution and compare its results with the results of 5788 computer-generated networks.

  1. Optimized Affinity Capture of Yeast Protein Complexes.

    Science.gov (United States)

    LaCava, John; Fernandez-Martinez, Javier; Hakhverdyan, Zhanna; Rout, Michael P

    2016-01-01

    Here, we describe an affinity isolation protocol. It uses cryomilled yeast cell powder for producing cell extracts and antibody-conjugated paramagnetic beads for affinity capture. Guidelines for determining the optimal extraction solvent composition are provided. Captured proteins are eluted in a denaturing solvent (sodium dodecyl sulfate polyacrylamide gel electrophoresis sample buffer) for gel-based proteomic analyses. Although the procedures can be modified to use other sources of cell extract and other forms of affinity media, to date we have consistently obtained the best results with the method presented. PMID:27371596

  2. Affinity Proteomics in the mountains: Alpbach 2015.

    Science.gov (United States)

    Taussig, Michael J

    2016-09-25

    The 2015 Alpbach Workshop on Affinity Proteomics, organised by the EU AFFINOMICS consortium, was the 7th workshop in this series. As in previous years, the focus of the event was the current state of affinity methods for proteome analysis, including complementarity with mass spectrometry, progress in recombinant binder production methods, alternatives to classical antibodies as affinity reagents, analysis of proteome targets, industry focus on biomarkers, and diagnostic and clinical applications. The combination of excellent science with Austrian mountain scenery and winter sports engender an atmosphere that makes this series of workshops exceptional. The articles in this Special Issue represent a cross-section of the presentations at the 2015 meeting. PMID:27118167

  3. Corner Transfer Matrices and Quantum Affine Algebras

    CERN Document Server

    Foda, O E; Foda, Omar; Miwa, Tetsuji

    1992-01-01

    Let H be the corner-transfer-matrix Hamiltonian for the six-vertex model in the anti-ferroelectric regime. It acts on the infinite tensor product W = V . V . V ....., where is the 2-dimensional irreducible representation of the quantum affine sl(2). We observe that H is the derivation of quantum affine sl(2), and conjecture that the eigenvectors of H form the level-1 vacuum representation of quantum affine sl(2). We report on checks in support of our conjecture.

  4. From Crescent to Mature Virion: Vaccinia Virus Assembly and Maturation

    Directory of Open Access Journals (Sweden)

    Liang Liu

    2014-10-01

    Full Text Available Vaccinia virus (VACV has achieved unprecedented success as a live viral vaccine for smallpox which mitigated eradication of the disease. Vaccinia virus has a complex virion morphology and recent advances have been made to answer some of the key outstanding questions, in particular, the origin and biogenesis of the virion membrane, the transformation from immature virion (IV to mature virus (MV, and the role of several novel genes, which were previously uncharacterized, but have now been shown to be essential for VACV virion formation. This new knowledge will undoubtedly contribute to the rational design of safe, immunogenic vaccine candidates, or effective antivirals in the future. This review endeavors to provide an update on our current knowledge of the VACV maturation processes with a specific focus on the initiation of VACV replication through to the formation of mature virions.

  5. Affinity improvement by fine tuning of single-chain variable fragment against aflatoxin B1.

    Science.gov (United States)

    Min, Won-Ki; Na, Kang-In; Yoon, Jung-Hyun; Heo, Yoon-Jee; Lee, Daesang; Kim, Sung-Gun; Seo, Jin-Ho

    2016-10-15

    Aflatoxin B1 (AFB1) produced in Aspergillus flavus is a major hepatocarcinogen found in foods and feed. For effective immunological detection of AFB1 at low concentrations, the development of high affinity antibody for AFB1 is required. Previously, an affinity-maturated single-chain variable fragment containing 6 mutations (scFv-M37) was isolated from an artificial mutagenic library, which showed a 9-fold higher affinity than its wild type scFv. In this study, the effect of the 6 mutated residues on the affinity improvement was characterized using surface plasmon resonance analysis, which identified a deleterious mutation (VH-A110T) located on a framework region of the scFv-M37. The back mutation of VH-A110T resulted in a 3.2-fold affinity improvement, which was attributed to decrease of dissociation rate constant (kd) in interaction between AFB1 and the back mutant scFv. The biophysical analyses using circular dichroism and gel filtration revealed that the back mutation of VH-A110T caused a subtle conformational change of the scFv toward tighter binding to AFB1. PMID:27173568

  6. Sustaining Exploration in Mature Basins

    International Nuclear Information System (INIS)

    Exploration is a business like any other business driven by opportunity, resources and expectation of profit. Therefore, exploration will thrive anywhere the opportunities are significant, the resources are available and the outlook for profit (or value creation) is good. To sustain exploration activities anywhere, irrespective of the environment, there must be good understanding of the drivers of these key investment criteria. This paper will examine these investment criteria as they relate to exploration business and address the peculiarity of exploration in mature basin. Mature basins are unique environment that lends themselves a mix of fears, paradigms and realities, particularly with respect to the perception of value. To sustain exploration activities in a mature basin, we need to understand these perceptions relative to the true drivers of profitability. Exploration in the mature basins can be as profitable as exploration in emerging basins if the dynamics of value definition-strategic and fiscal values are understood by operators, regulators and co ventures alike. Some suggestions are made in this presentation on what needs to be done in addressing these dynamic investment parameters and sustaining exploration activities in mature basins

  7. 玉米田四代棉铃虫老熟幼虫空间分布型应用%Spatial Distribution Pattern Application of Fourth-Generation Mature Larvae of Cotton Bollworm (Helicoverpa armigera Hübner) in Maize Field

    Institute of Scientific and Technical Information of China (English)

    李贺年; 齐巧丽; 李德新; 姚克荣

    2011-01-01

    [ Objective ] The paper was to study the spatial distribution pattern of fourth-generation mature larvae of cotton bollworm in maize field. [ Method] The plots with different occurrence densities of fourth-generation cotton bollworm were investigated during August to September in 2009. Six groups of sampling data were obtained, and seven indicators were used to determined its spatial distribution pattern. including aggregation index method, lwao method and Taylor method, etc. [ Result] Aggregation index test showed that in all plots, Moore I < 0,Lloyod m*/m < 1, Kuno Ca <0, diffusion coefficient C < 1, diffusion index Iδ < 1, negative binomial distribution K <0, indicating that mature larvae of cotton bollworm showed uniform distribution in summer maize. Iwao regression equation of fourth-generation mature larvae of cotton bollworm in summer maize was m * =0. 090 6 +0. 766 9m, r =0.986 3, indicating that the basic components of cotton bollworm distribution was single individual, and mature larvae of cotton bollworm in summer maize showed uniform distribution. The optimal sampling number of fourth-generation mature larvae of cotton bollwonn in maize under different population densities could be calculated using formula N1 =( 1. 090 6/m - 0. 233 1 )/D2. [ Conclusion ] The result provided basis for accurate evaluation of population quantities and variation law of cotton bollworm, as well as prediction and control of the pest.%[目的]研究玉米田四代棉铃虫老熟幼虫空间分布型.[方法]于2009年8~9月,对第4代棉铃虫不同发生密度地块进行调查,取得了6组样本资料,应用聚集度指标法、Iwao法和Taylor法等7种指标分析,对其空间分布型进行检验.[结果]聚集度指标的检验结果表明:所有样地Moore I<0,Lloyod m*/m<1,Kuno Ca<0,扩散系数C<1,扩散型指数 Iδ<1,负二项分布,K<0,表明棉铃虫老熟幼虫在夏玉米上均呈均匀分布.棉铃虫第4代老熟幼虫在夏

  8. Automorphisms in Birational and Affine Geometry

    CERN Document Server

    Ciliberto, Ciro; Flenner, Hubert; McKernan, James; Prokhorov, Yuri; Zaidenberg, Mikhail

    2014-01-01

    The main focus of this volume is on the problem of describing the automorphism groups of affine and projective varieties, a classical subject in algebraic geometry where, in both cases, the automorphism group is often infinite dimensional. The collection covers a wide range of topics and is intended for researchers in the fields of classical algebraic geometry and birational geometry (Cremona groups) as well as affine geometry with an emphasis on algebraic group actions and automorphism groups. It presents original research and surveys and provides a valuable overview of the current state of the art in these topics. Bringing together specialists from projective, birational algebraic geometry and affine and complex algebraic geometry, including Mori theory and algebraic group actions, this book is the result of ensuing talks and discussions from the conference “Groups of Automorphisms in Birational and Affine Geometry” held in October 2012, at the CIRM, Levico Terme, Italy. The talks at the conference high...

  9. Synthesis of a New Series of Bone Affinity Compounds

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A new series of bone affinity compounds were synthesized by linking chrysophanol with 5-fluorouracil derivatives. Their bone affinity was established by hydroxyapafive (HA)affinity experiment in vitro, and their cytostatic effects were shown by the MTT assay.

  10. On Affine Fusion and the Phase Model

    OpenAIRE

    Walton, Mark A.

    2012-01-01

    A brief review is given of the integrable realization of affine fusion discovered recently by Korff and Stroppel. They showed that the affine fusion of the $su(n)$ Wess-Zumino-Novikov-Witten (WZNW) conformal field theories appears in a simple integrable system known as the phase model. The Yang-Baxter equation leads to the construction of commuting operators as Schur polynomials, with noncommuting hopping operators as arguments. The algebraic Bethe ansatz diagonalizes them, revealing a connec...

  11. Purely affine elementary su(N) fusions

    OpenAIRE

    Rasmussen, Jorgen; Walton, Mark A.

    2001-01-01

    We consider three-point couplings in simple Lie algebras -- singlets in triple tensor products of their integrable highest weight representations. A coupling can be expressed as a linear combination of products of finitely many elementary couplings. This carries over to affine fusion, the fusion of Wess-Zumino-Witten conformal field theories, where the expressions are in terms of elementary fusions. In the case of su(4) it has been observed that there is a purely affine elementary fusion, i.e...

  12. Fan affinity laws from a collision model

    International Nuclear Information System (INIS)

    The performance of a fan is usually estimated using hydrodynamical considerations. The calculations are long and involved and the results are expressed in terms of three affinity laws. In this paper we use kinetic theory to attack this problem. A hard sphere collision model is used, and subsequently a correction to account for the flow behaviour of air is incorporated. Our calculations prove the affinity laws and provide numerical estimates of the air delivery, thrust and drag on a rotating fan. (paper)

  13. A MEMS Dielectric Affinity Glucose Biosensor

    OpenAIRE

    Xian HUANG; Li, SiQi; Davis, Erin; Li, Dachao; Wang, Qian; Lin, Qiao

    2013-01-01

    Continuous glucose monitoring (CGM) sensors based on affinity detection are desirable for long-term and stable glucose management. However, most affinity sensors contain mechanical moving structures and complex design in sensor actuation and signal readout, limiting their reliability in subcutaneously implantable glucose detection. We have previously demonstrated a proof-of-concept dielectric glucose sensor that measured pre-mixed glucose-sensitive polymer solutions at various glucose concent...

  14. Cheese maturity assessment using ultrasonics.

    Science.gov (United States)

    Benedito, J; Carcel, J; Clemente, G; Mulet, A

    2000-02-01

    The relationship between Mahon cheese maturity and ultrasonic velocity was examined. Moisture and textural properties were used as maturity indicators. The ultrasonic velocity of the cheese varied between 1630 and 1740 m/s, increasing with the curing time mainly because of loss of water, which also produced an increase of the textural properties. Because of the nature of low-intensity ultrasonics, velocity was better related to those textural parameters that involved small displacements. Ultrasonic velocity decreased with increasing temperature because of the negative temperature coefficient of the ultrasonic velocity of fat and the melting of fat. These results highlight the potential use of ultrasonic velocity measurements to rapidly and nondestructively assess cheese maturity. PMID:10714857

  15. Affine modifications and affine hypersurfaces with a very transitive automorphism group

    OpenAIRE

    Kaliman, Shulim; ZAIDENBERG, MIKHAIL

    1998-01-01

    We study a kind of modification of an affine domain which produces another affine domain. First appeared in passing in the basic paper of O. Zariski (1942), it was further considered by E.D. Davis (1967). The first named author applied its geometric counterpart to construct contractible smooth affine varieties non-isomorphic to Euclidean spaces. Here we provide certain conditions which guarantee preservation of the topology under a modification. As an application, we show that the group of bi...

  16. Affinity approaches in RNAi-based therapeutics purification.

    Science.gov (United States)

    Pereira, Patrícia; Queiroz, João A; Figueiras, Ana; Sousa, Fani

    2016-05-15

    The recent investigation on RNA interference (RNAi) related mechanisms and applications led to an increased awareness of the importance of RNA in biology. Nowadays, RNAi-based technology has emerged as a potentially powerful tool for silencing gene expression, being exploited to develop new therapeutics for treating a vast number of human disease conditions, as it is expected that this technology can be translated onto clinical applications in a near future. This approach makes use of a large number of small (namely short interfering RNAs, microRNAs and PIWI-interacting RNAs) and long non-coding RNAs (ncRNAs), which are likely to have a crucial role as the next generation therapeutics. The commercial and biomedical interest in these RNAi-based therapy applications have fostered the need to develop innovative procedures to easily and efficiently purify RNA, aiming to obtain the final product with high purity degree, good quality and biological activity. Recently, affinity chromatography has been applied to ncRNAs purification, in view of the high specificity. Therefore, this article intends to review the biogenesis pathways of regulatory ncRNAs and also to discuss the most significant and recent developments as well as applications of affinity chromatography in the challenging task of purifying ncRNAs. In addition, the importance of affinity chromatography in ncRNAs purification is addressed and prospects for what is forthcoming are presented. PMID:26830537

  17. Immune and endocrine responses of adult spring Chinook salmon during freshwater migration and sexual maturation

    Science.gov (United States)

    Maule, A.G.; Schrock, R.M.; Slater, C.; Fitzpatrick, M.S.; Schreck, C. B.

    1996-01-01

    The immune –endocrine responses in spring chinook salmon (Oncorhynchus tshawytscha) were examined during their freshwater migration and final maturation. In 1990, migrating fish had high plasma cortisol titres (means 200 ng ml−1) and generated relatively few antibody-producing cells (APC) from peripheral blood leukocytes (PBL) (100 –200 per culture). After three weeks acclimation in constant environmental conditions, plasma cortisol was reduced and APC increased. There were no changes in number or affinity of glucocorticoid receptors. Concentrations of several sex steroids correlated with APC in females, but there were no such correlations in males. In 1993, fish in a hatchery had significantly greater cortisol concentrations in primary circulation than in secondary circulation, but sex steroid concentrations did not differ between circulations. Mean lysozyme activity in the primary and secondary circulation did not differ in June. In August, activity in the primary circulation was significantly less than that of the secondary, perhaps the result of acute stress associated with sampling. While some sex steroids correlated with lysozyme activity, the fact that in both years all endocrine and immune variables that correlated with each other also correlated with the date of sample, raises the question as to whether or not these are cause-and-effect relations.

  18. Leadership Development and Organizational Maturity.

    Science.gov (United States)

    Iannuzzi, Patricia

    1992-01-01

    Urges the design and implementation of strategies in academic libraries for the development of leadership potential. Discusses the components of organizations that lead to organizational maturity, and calls for library leaders with vision, skill, and commitment to nurture an organizational culture that emphasizes leadership development. (20…

  19. Public Sector IS Maturity Models

    DEFF Research Database (Denmark)

    Zinner Henriksen, Helle; Andersen, Kim Normann; Medaglia, Rony

    2011-01-01

    Online applications and processing of tax forms, driver licenses, and construction permits are examples of where policy attention and research have been united in efforts aiming to categorize the maturity level of e-services. Less attention has been attributed to policy areas with continuous online...

  20. Affinity purification of aprotinin from bovine lung.

    Science.gov (United States)

    Xin, Yu; Liu, Lanhua; Chen, Beizhan; Zhang, Ling; Tong, Yanjun

    2015-05-01

    An affinity protocol for the purification of aprotinin from bovine lung was developed. To simulate the structure of sucrose octasulfate, a natural specific probe for aprotinin, the affinity ligand was composed of an acidic head and a hydrophobic stick, and was then linked with Sepharose. The sorbent was then subjected to adsorption analysis with pure aprotinin. The purification process consisted of one step of affinity chromatography and another step of ultrafiltration. Then purified aprotinin was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, trypsin inhibitor activity, gel-filtration, and thin-layer chromatography analysis. As calculated, the theoretical maximum adsorption (Qmax ) of the affinity sorbent was 25,476.0 ± 184.8 kallikrein inactivator unit/g wet gel; the dissociation constant of the complex "immobilized ligand-aprotinin" (Kd ) was 4.6 ± 0.1 kallikrein inactivator unit/mL. After the affinity separation of bovine lung aprotinin, reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and gel-filtration chromatography revealed that the protein was a single polypeptide, and the purities were ∼ 97 and 100%, respectively; the purified peptide was also confirmed with aprotinin standard by gel-filtration chromatography and thin-layer chromatography. After the whole purification process, protein, and bioactivity recoveries were 2.2 and 92.6%, respectively; and the specific activity was up to 15,907.1 ± 10.2 kallikrein inactivator unit/mg. PMID:25677462

  1. Temperature Cycles Induce Early Maturation in Channel Catfish

    Science.gov (United States)

    A major impediment in improvement of channel catfish by selective breeding is that a high percent of fish do not spawn until the third year. If the generation time could be shortened, genetic improvement could be achieved at a faster rate. The conditions that lead to sexual maturation in fish have...

  2. Quantum image encryption based on generalized affine transform and logistic map

    Science.gov (United States)

    Liang, Hao-Ran; Tao, Xiang-Yang; Zhou, Nan-Run

    2016-07-01

    Quantum circuits of the generalized affine transform are devised based on the novel enhanced quantum representation of digital images. A novel quantum image encryption algorithm combining the generalized affine transform with logistic map is suggested. The gray-level information of the quantum image is encrypted by the XOR operation with a key generator controlled by the logistic map, while the position information of the quantum image is encoded by the generalized affine transform. The encryption keys include the independent control parameters used in the generalized affine transform and the logistic map. Thus, the key space is large enough to frustrate the possible brute-force attack. Numerical simulations and analyses indicate that the proposed algorithm is realizable, robust and has a better performance than its classical counterpart in terms of computational complexity.

  3. Quantum image encryption based on generalized affine transform and logistic map

    Science.gov (United States)

    Liang, Hao-Ran; Tao, Xiang-Yang; Zhou, Nan-Run

    2016-03-01

    Quantum circuits of the generalized affine transform are devised based on the novel enhanced quantum representation of digital images. A novel quantum image encryption algorithm combining the generalized affine transform with logistic map is suggested. The gray-level information of the quantum image is encrypted by the XOR operation with a key generator controlled by the logistic map, while the position information of the quantum image is encoded by the generalized affine transform. The encryption keys include the independent control parameters used in the generalized affine transform and the logistic map. Thus, the key space is large enough to frustrate the possible brute-force attack. Numerical simulations and analyses indicate that the proposed algorithm is realizable, robust and has a better performance than its classical counterpart in terms of computational complexity.

  4. To Mature or not to Mature: The Information Systems Conundrum

    Directory of Open Access Journals (Sweden)

    Carl Marnewick

    2013-12-01

    Full Text Available Research has been done within the South African information technology (IT industry over the last decade with regard to project management maturity (PMM and the impact it has on delivering information systems (IS projects successfully. The research was done to determine whether IS PMM per knowledge area has improved over the last decade. It investigates if there is a correlation between maturity levels and project success. Four independent surveys over the last decade focused on IS PMM and the longitudinal analysis provides a benchmark for whether IS PMM has increased or not. This article focuses on whether certain knowledge areas are more of a problem within the IT industry and to determine what the overall IS PMM is. The longitudinal analysis indicates trends and highlights areas of concern. It indicates that most IT companies are still operating at level 3 and that risk and procurement management are the knowledge areas of concern. A comparative analysis indicates that there is no difference between South African and international maturity levels. The results provide a South African perspective of IS PMM. It highlights that risk management is still a knowledge area that is neglected and that emphasis must be placed on managing risk within IT projects.

  5. Congophilicity (Congo red affinity) of different beta2-microglobulin conformations characterized by dye affinity capillary electrophoresis

    DEFF Research Database (Denmark)

    Heegaard, N H; Sen, J W; Nissen, Mogens Holst

    2000-01-01

    The amyloidogenic protein beta-microglobulin was characterized by affinity capillary electrophoresis (CE). CE could separate conformational variants of beta2-microglobulin and with the amyloid-specific dye Congo red as a buffer additive it was possible to measure different Congo red-affinities of...

  6. Jerónimo Martins Distribuição : are mature export markets addressable?

    OpenAIRE

    Oliveira, Teresa Almada e Melo Gomes de

    2015-01-01

    The main goal of this research is to uncover the main challenges of the export business, mainly in the perspective of small-country companies, like the Portuguese, and potential resolutions, in order to excel the development of external markets, namely mature and / or non-affinity ones. Mainly through the insights of the major exporters in the Portuguese food industry and associated government entities, the main conclusion of the study is that likely, previous strategies deployed in emerging ...

  7. On Affine Fusion and the Phase Model

    Directory of Open Access Journals (Sweden)

    Mark A. Walton

    2012-11-01

    Full Text Available A brief review is given of the integrable realization of affine fusion discovered recently by Korff and Stroppel. They showed that the affine fusion of the su(n Wess-Zumino-Novikov-Witten (WZNW conformal field theories appears in a simple integrable system known as the phase model. The Yang-Baxter equation leads to the construction of commuting operators as Schur polynomials, with noncommuting hopping operators as arguments. The algebraic Bethe ansatz diagonalizes them, revealing a connection to the modular S matrix and fusion of the su(n WZNW model. The noncommutative Schur polynomials play roles similar to those of the primary field operators in the corresponding WZNW model. In particular, their 3-point functions are the su(n fusion multiplicities. We show here how the new phase model realization of affine fusion makes obvious the existence of threshold levels, and how it accommodates higher-genus fusion.

  8. On affine fusion and the phase model

    CERN Document Server

    Walton, Mark A

    2012-01-01

    A brief review is given of the integrable realization of affine fusion discovered recently by Korff and Stroppel. They showed that the affine fusion of the su(n) Wess-Zumino-Novikov-Witten (WZNW) conformal field theories appears in a simple integrable system known as the phase model. The algebraic Bethe ansatz constructs the commuting operators of the phase model as Schur polynomials, with non-commuting hopping operators as arguments. These non-commutative Schur polynomials play roles similar to those of the primary field operators in the corresponding WZNW model. In particular, their 3-point functions are the su(n) fusion multiplicities. We show here how the new phase model realization of affine fusion makes obvious the existence of threshold levels, and how it accommodates higher-genus fusion.

  9. Low skilled, mature workers and lifelong learning

    DEFF Research Database (Denmark)

    Hansen, Leif Emil

    There is some evidence that mature industrial workers have specific profiles, views and values, when it comes to learning and participation in educational processes and programs. It seems as if the kind of education they are motivated for should be: mimetic, minimalistic and instrumental. This is......There is some evidence that mature industrial workers have specific profiles, views and values, when it comes to learning and participation in educational processes and programs. It seems as if the kind of education they are motivated for should be: mimetic, minimalistic and instrumental....... (in school – not in practical work!). In a Danish context you will also very often see dyslexia and various forms of functional illiteracy etc. The group’s attitude towards lifelong learning is also influenced by a socio-cultural heritage: they are typically trained (brought up, socialized) through...... generations to develop a ’reactive’ attitude (‘the most important competence is to learn to do what you are told’). In contrast to this ‘post-industrialism’ requires a ’pro-active’ attitude (‘everybody should develop will and capacity to tell (oneself and others) what to do’). How to deal...

  10. Affine Projection Algorithm Using Regressive Estimated Error

    OpenAIRE

    Zhang, Shu; Zhi, Yongfeng

    2011-01-01

    An affine projection algorithm using regressive estimated error (APA-REE) is presented in this paper. By redefining the iterated error of the affine projection algorithm (APA), a new algorithm is obtained, and it improves the adaptive filtering convergence rate. We analyze the iterated error signal and the stability for the APA-REE algorithm. The steady-state weights of the APA-REE algorithm are proved to be unbiased and consist. The simulation results show that the proposed algorithm has a f...

  11. Control and estimation of piecewise affine systems

    CERN Document Server

    Xu, Jun

    2014-01-01

    As a powerful tool to study nonlinear systems and hybrid systems, piecewise affine (PWA) systems have been widely applied to mechanical systems. Control and Estimation of Piecewise Affine Systems presents several research findings relating to the control and estimation of PWA systems in one unified view. Chapters in this title discuss stability results of PWA systems, using piecewise quadratic Lyapunov functions and piecewise homogeneous polynomial Lyapunov functions. Explicit necessary and sufficient conditions for the controllability and reachability of a class of PWA systems are

  12. Periodic cyclic homology of affine Hecke algebras

    CERN Document Server

    Solleveld, Maarten

    2009-01-01

    This is the author's PhD-thesis, which was written in 2006. The version posted here is identical to the printed one. Instead of an abstract, the short list of contents: Preface 5 1 Introduction 9 2 K-theory and cyclic type homology theories 13 3 Affine Hecke algebras 61 4 Reductive p-adic groups 103 5 Parameter deformations in affine Hecke algebras 129 6 Examples and calculations 169 A Crossed products 223 Bibliography 227 Index 237 Samenvatting 245 Curriculum vitae 253

  13. The Affine q-Schur algebra

    OpenAIRE

    Green, R. M.

    1997-01-01

    We introduce an analogue of the $q$-Schur algebra associated to Coxeter systems of type $\\hat A_{n-1}$. We give two constructions of this algebra. The first construction realizes the algebra as a certain endomorphism algebra arising from an affine Hecke algebra of type $\\hat A_{r-1}$, where $n \\geq r$. This generalizes the original $q$-Schur algebra as defined by Dipper and James, and the new algebra contains the ordinary $q$-Schur algebra and the affine Hecke algebra as subalgebras. Using th...

  14. Contribution of a p75 interleukin 2 binding peptide to a high-affinity interleukin 2 receptor complex

    International Nuclear Information System (INIS)

    There are at least two forms of cellular receptors for interleukin 2(IL-2); one with a very high affinity and the other with a lower affinity. The authors identified a non-Tac IL-2 binding peptide with a relative molecular weight of 75,000 (p75). Cell lines bearing either the p55 Tac or the p75 peptide alone manifested low-affinity IL-2 binding, whereas a cell line bearing both peptides manifested both high- and low-affinity receptors. Cross-linking studies were performed with 125I-labeled IL-2. After the internalization of labeled IL-2 through high-affinity receptors, the p75 peptide could not be detected by cross-linking studies. Furthermore, fusion of cell membranes from low-affinity IL-2 binding cell lines bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generated hybrid membranes bearing high-affinity receptors. These results suggest a multichain model for the high-affinity Il-2 receptor in which high-affinity receptors would be expressed when both Tac and p75 Il-2 binding peptides are present and associated in a receptor complex

  15. The enrichment industry reaches maturity

    International Nuclear Information System (INIS)

    As the nuclear power industry enters the 1980s, uranium enrichment supply can no longer be considered one of the critical problem areas of the nuclear fuel cycle. It has become an industrial and commercial activity which has reached a high degree of maturity. Three main aspects of this maturity are discussed: 1. the availability of enrichment services from several facilities with very diverse ownership; 2. the involvement of private industry, especially in Europe, and the application of normal commercial rules to enrichment contracts; 3. the ability of the enrichment industry to cope with recent setbacks in the advancement of nuclear power programmes whilst carrying out an active research and development programme that will help to ensure its future technical and economic viability. (U.K.)

  16. Maturation of the adolescent brain

    Directory of Open Access Journals (Sweden)

    Arain M

    2013-04-01

    Full Text Available Mariam Arain, Maliha Haque, Lina Johal, Puja Mathur, Wynand Nel, Afsha Rais, Ranbir Sandhu, Sushil Sharma Saint James School of Medicine, Kralendijk, Bonaire, The Netherlands Abstract: Adolescence is the developmental epoch during which children become adults – intellectually, physically, hormonally, and socially. Adolescence is a tumultuous time, full of changes and transformations. The pubertal transition to adulthood involves both gonadal and behavioral maturation. Magnetic resonance imaging studies have discovered that myelinogenesis, required for proper insulation and efficient neurocybernetics, continues from childhood and the brain's region-specific neurocircuitry remains structurally and functionally vulnerable to impulsive sex, food, and sleep habits. The maturation of the adolescent brain is also influenced by heredity, environment, and sex hormones (estrogen, progesterone, and testosterone, which play a crucial role in myelination. Furthermore, glutamatergic neurotransmission predominates, whereas gamma-aminobutyric acid neurotransmission remains under construction, and this might be responsible for immature and impulsive behavior and neurobehavioral excitement during adolescent life. The adolescent population is highly vulnerable to driving under the influence of alcohol and social maladjustments due to an immature limbic system and prefrontal cortex. Synaptic plasticity and the release of neurotransmitters may also be influenced by environmental neurotoxins and drugs of abuse including cigarettes, caffeine, and alcohol during adolescence. Adolescents may become involved with offensive crimes, irresponsible behavior, unprotected sex, juvenile courts, or even prison. According to a report by the Centers for Disease Control and Prevention, the major cause of death among the teenage population is due to injury and violence related to sex and substance abuse. Prenatal neglect, cigarette smoking, and alcohol consumption may also

  17. Maturation of the adolescent brain

    OpenAIRE

    Arain M; Haque M; Johal L; Mathur P; Nel W; Rais A; Sandhu R; Sharma S

    2013-01-01

    Mariam Arain, Maliha Haque, Lina Johal, Puja Mathur, Wynand Nel, Afsha Rais, Ranbir Sandhu, Sushil Sharma Saint James School of Medicine, Kralendijk, Bonaire, The Netherlands Abstract: Adolescence is the developmental epoch during which children become adults – intellectually, physically, hormonally, and socially. Adolescence is a tumultuous time, full of changes and transformations. The pubertal transition to adulthood involves both gonadal and behavioral maturation. Magnetic resonance...

  18. Structural correlates of affinity in fetal versus adult endplate nicotinic receptors

    Science.gov (United States)

    Nayak, Tapan Kumar; Chakraborty, Srirupa; Zheng, Wenjun; Auerbach, Anthony

    2016-04-01

    Adult-type nicotinic acetylcholine receptors (AChRs) mediate signalling at mature neuromuscular junctions and fetal-type AChRs are necessary for proper synapse development. Each AChR has two neurotransmitter binding sites located at the interface of a principal and a complementary subunit. Although all agonist binding sites have the same core of five aromatic amino acids, the fetal site has ~30-fold higher affinity for the neurotransmitter ACh. Here we use molecular dynamics simulations of adult versus fetal homology models to identify complementary-subunit residues near the core that influence affinity, and use single-channel electrophysiology to corroborate the results. Four residues in combination determine adult versus fetal affinity. Simulations suggest that at lower-affinity sites, one of these unsettles the core directly and the others (in loop E) increase backbone flexibility to unlock a key, complementary tryptophan from the core. Swapping only four amino acids is necessary and sufficient to exchange function between adult and fetal AChRs.

  19. Maturity model for enterprise interoperability

    Science.gov (United States)

    Guédria, Wided; Naudet, Yannick; Chen, David

    2015-01-01

    Historically, progress occurs when entities communicate, share information and together create something that no one individually could do alone. Moving beyond people to machines and systems, interoperability is becoming a key factor of success in all domains. In particular, interoperability has become a challenge for enterprises, to exploit market opportunities, to meet their own objectives of cooperation or simply to survive in a growing competitive world where the networked enterprise is becoming a standard. Within this context, many research works have been conducted over the past few years and enterprise interoperability has become an important area of research, ensuring the competitiveness and growth of European enterprises. Among others, enterprises have to control their interoperability strategy and enhance their ability to interoperate. This is the purpose of the interoperability assessment. Assessing interoperability maturity allows a company to know its strengths and weaknesses in terms of interoperability with its current and potential partners, and to prioritise actions for improvement. The objective of this paper is to define a maturity model for enterprise interoperability that takes into account existing maturity models while extending the coverage of the interoperability domain. The assessment methodology is also presented. Both are demonstrated with a real case study.

  20. AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies.

    Science.gov (United States)

    Meyer, Steffen; Woodward, Martin; Hertel, Christina; Vlaicu, Philip; Haque, Yasmin; Kärner, Jaanika; Macagno, Annalisa; Onuoha, Shimobi C; Fishman, Dmytro; Peterson, Hedi; Metsküla, Kaja; Uibo, Raivo; Jäntti, Kirsi; Hokynar, Kati; Wolff, Anette S B; Krohn, Kai; Ranki, Annamari; Peterson, Pärt; Kisand, Kai; Hayday, Adrian

    2016-07-28

    APS1/APECED patients are defined by defects in the autoimmune regulator (AIRE) that mediates central T cell tolerance to many self-antigens. AIRE deficiency also affects B cell tolerance, but this is incompletely understood. Here we show that most APS1/APECED patients displayed B cell autoreactivity toward unique sets of approximately 100 self-proteins. Thereby, autoantibodies from 81 patients collectively detected many thousands of human proteins. The loss of B cell tolerance seemingly occurred during antibody affinity maturation, an obligatorily T cell-dependent step. Consistent with this, many APS1/APECED patients harbored extremely high-affinity, neutralizing autoantibodies, particularly against specific cytokines. Such antibodies were biologically active in vitro and in vivo, and those neutralizing type I interferons (IFNs) showed a striking inverse correlation with type I diabetes, not shown by other anti-cytokine antibodies. Thus, naturally occurring human autoantibodies may actively limit disease and be of therapeutic utility. PMID:27426947

  1. Crossing Chris: Some Markerian Affinities

    Directory of Open Access Journals (Sweden)

    Adrian Martin

    2010-01-01

    -pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

    Abstract (E: This essay creatively explores a group of artists, writers, and other special individuals whose work or life story can be described as having an intriguing affinity with the protean career of Chris Marker. Avoiding the ‘usual suspects’ (such as Godard or Sebald, it discusses gossip columnist Milt Machlin, record collector Harry Smith, painter Gianfranco Baruchello, writer-filmmaker Edgardo Cozarinsky, and several others. From this constellation, a particular view of Markerian poetics emerges, touching upon the meanings of anonymity, storytelling, history and archiving.

     

    Abstract (F: Cet essai brosse de manière créative le portrait d’un groupe d'artistes, d'écrivains et d'autres personnes particulières dont le travail ou la biographie peuvent être décrits comme montrant une étrange mais certaine connivence avec la carrière protéiforme de Chris Marker. Evitant les lieux communs (comme Godard ou Sebald, cet article trace des références moins attendues :

  2. On integral forms for vertex algebras associated with affine Lie algebras and lattices

    OpenAIRE

    McRae, Robert

    2014-01-01

    We revisit the construction of integral forms for vertex (operator) algebras $V_L$ based on even lattices $L$ using generators instead of bases, and we construct integral forms for $V_L$-modules. We construct integral forms for vertex (operator) algebras based on highest-weight modules for affine Lie algebras and we exhibit natural generating sets. For vertex operator algebras in general, we give conditions showing when an integral form contains the standard conformal vector generating the Vi...

  3. Thermal Maturation of Gas Shale Systems

    Science.gov (United States)

    Bernard, Sylvain; Horsfield, Brian

    2014-05-01

    Shale gas systems serve as sources, reservoirs, and seals for unconventional natural gas accumulations. These reservoirs bring numerous challenges to geologists and petroleum engineers in reservoir characterization, most notably because of their heterogeneous character due to depositional and diagenetic processes but also because of their constituent rocks' fine-grained nature and small pore size -- much smaller than in conventional sandstone and carbonate reservoirs. Significant advances have recently been achieved in unraveling the gaseous hydrocarbon generation and retention processes that occur within these complex systems. In addition, cutting-edge characterization technologies have allowed precise documentation of the spatial variability in chemistry and structure of thermally mature organic-rich shales at the submicrometer scale, revealing the presence of geochemical heterogeneities within overmature gas shale samples and, notably, the presence of nanoporous pyrobitumen. Such research advances will undoubtedly lead to improved performance, producibility, and modeling of such strategic resources at the reservoir scale.

  4. Braided affine geometry and q-analogs of wave operators

    International Nuclear Information System (INIS)

    The main goal of this review is to compare different approaches to constructing the geometry associated with a Hecke type braiding (in particular, with that related to the quantum group Uq(sl(n))). We place emphasis on the affine braided geometry related to the so-called reflection equation algebra (REA). All objects of such a type of geometry are defined in the spirit of affine algebraic geometry via polynomial relations on generators. We begin by comparing the Poisson counterparts of 'quantum varieties' and describe different approaches to their quantization. Also, we exhibit two approaches to introducing q-analogs of vector bundles and defining the Chern-Connes index for them on quantum spheres. In accordance with the Serre-Swan approach, the q-vector bundles are treated as finitely generated projective modules over the corresponding quantum algebras. Besides, we describe the basic properties of the REA used in this construction and compare different ways of defining q-analogs of partial derivatives and differentials on the REA and algebras close to them. In particular, we present a way of introducing a q-differential calculus via Koszul type complexes. The elements of the q-calculus are applied to defining q-analogs of some relativistic wave operators. (topical review)

  5. General super Virasoro construction on affine G

    International Nuclear Information System (INIS)

    We consider a bosonic current algebra and a theory of free fermions and construct a general N = 1 super Virasoro current algebra. We obtain a master-set of equations which comprises the bosonic master equation for general Virasoro construction on affine G. As an illustration we study the case of the group SU(2). (author). 13 refs

  6. Classification of neocortical interneurons using affinity propagation

    Directory of Open Access Journals (Sweden)

    Roberto eSantana

    2013-12-01

    Full Text Available In spite of over a century of research on cortical circuits, it is still unknown how many classes of cortical neurons exist. Neuronal classification has been a difficult problem because it is unclear what a neuronal cell class actually is and what are the best characteristics are to define them. Recently, unsupervised classifications using cluster analysis based on morphological, physiological or molecular characteristics, when applied to selected datasets, have provided quantitative and unbiased identification of distinct neuronal subtypes. However, better and more robust classification methods are needed for increasingly complex and larger datasets. We explored the use of affinity propagation, a recently developed unsupervised classification algorithm imported from machine learning, which gives a representative example or exemplar for each cluster. As a case study, we applied affinity propagation to a test dataset of 337 interneurons belonging to four subtypes, previously identified based on morphological and physiological characteristics. We found that affinity propagation correctly classified most of the neurons in a blind, non-supervised manner. In fact, using a combined anatomical/physiological dataset, our algorithm differentiated parvalbumin from somatostatin interneurons in 49 out of 50 cases. Affinity propagation could therefore be used in future studies to validly classify neurons, as a first step to help reverse engineer neural circuits.

  7. Affinely Recursive Functions and Neural Networks

    Czech Academy of Sciences Publication Activity Database

    Kůrková, Věra; Kainen, P.C.

    Atlanta : Georgia Institute of Technology, 1994 - ( Ames , W.), s. 776-779 [IMACS World Congress /14./. Atlanta (US), 11.07.1994-15.07.1994] R&D Projects: GA AV ČR IA23057; GA ČR GA201/93/0427 Keywords : neural networks * affinely recursive functions

  8. Colliding waves in metric-affine gravity

    CERN Document Server

    García, A; Macías, A; Mielke, E W; Socorro, J; García, Alberto; Lämmerzahl, Claus; Macías, Alfredo; Mielke, Eckehard W.; Socorro, José

    1998-01-01

    We generalize the formulation of the colliding gravitational waves to metric-affine theories and present an example of such kind of exact solutions. The plane waves are equipped with five symmetries and the resulting geometry after the collision possesses two spacelike Killing vectors.

  9. Diagnostics of school maturity and school readiness

    OpenAIRE

    SÝKOROVÁ, Štěpánka

    2011-01-01

    In my bachelor´s work I have focused on problems of school readiness and maturity. My objective was to asses the optimal school maturity in pre-school class. In the theoretical part I described the pre-school session, school maturity and readiness and its characteristics. I compared the different definitions of school readiness and maturity, as indicated in the literature. On the basis of the research and consultation I approached appropriate diagnostic materials for detecting the level of sc...

  10. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity

    DEFF Research Database (Denmark)

    Asti, Lorenzo; Uguzzoni, Guido; Marcatili, Paolo;

    2016-01-01

    The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high...... HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6), outperforming other sequence- and structure-based models....

  11. 7 CFR 51.1904 - Maturity classification.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Maturity classification. 51.1904 Section 51.1904... STANDARDS) United States Consumer Standards for Fresh Tomatoes Size and Maturity Classification § 51.1904 Maturity classification. Tomatoes which are characteristically red when ripe, but are not overripe or...

  12. Maturity Models Development in IS Research

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi; Andersen, Kim Normann

    2015-01-01

    Maturity models are widespread in IS research and in particular, IT practitioner communities. However, theoretically sound, methodologically rigorous and empirically validated maturity models are quite rare. This literature review paper focuses on the challenges faced during the development of...... maturity models. Specifically, it explores maturity models literature in IS and standard guidelines, if any to develop maturity models, challenges identified and solutions proposed. Our systematic literature review of IS publications revealed over hundred and fifty articles on maturity models. Extant...... literature reveals that researchers have primarily focused on developing new maturity models pertaining to domain-specific problems and/or new enterprise technologies. We find rampant re-use of the design structure of widely adopted models such as Nolan’s Stage of Growth Model, Crosby’s Grid, and Capability...

  13. Proliferative responses and binding properties of hematopoietic cells transfected with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor.

    OpenAIRE

    Gearing, D P; Ziegler, S F; Comeau, M R; Friend, D; Thoma, B; Cosman, D; Park, L.; Mosley, B

    1994-01-01

    Specific low-affinity receptors for leukemia inhibitory factor (LIF), oncostatin M (OSM; gp130), and ciliary neurotrophic factor (CNTF; receptor alpha, CNTFR alpha) may be utilized in various combinations to generate high-affinity binding sites and signal transduction. We have tested the ability of combinations of these receptors to transduce a proliferative signal in BAF-B03 cells. Coexpression of the LIF receptor and gp130 in these cells conferred high-affinity LIF and OSM binding and respo...

  14. Acute myeloid leukemia cells inhibit the differentiation and maturation of dendritic cells and induce the generation of regulatory T cells%急性髓系白血病细胞对树突状细胞分化、成熟和调节性T细胞生成的影响

    Institute of Scientific and Technical Information of China (English)

    Xingbing Wang; Xin Chen; Jun Liu; Zimin Sun; Shiang Huang

    2008-01-01

    Objective: To investigate the effects of soluble factors secreted by acute myeloid leukemia (AML) cells on the phenotypical and functional properties of DCs derived from normal mononuclear cells. Methods: Mononuclear cells were cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF), in the presence or absence of 24 h culture supernatants from fresh primary AML cells, to generate immature DCs. The maturation of DCs was induced by cytokines IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin-2 (PGE-2). The phenotypic alterations of DCs and DCs-primed CD4+ T cells were evaluated using flow cytometry. Precursor frequency (PF) was calculated to monitor the allostimulatory effects of DCs on CD4+ and CD8+ T cells. Results:AML cell supernatant-treated DCs showed significantly lower expression of co-stimulatory molecules CD80 and CD86, and reduced response to cytokines IL-1beta, IL-6, TNF-alpha,and PGE-2. The allostimulatory effects of AML cell supernatant-treated DCs on CD4+ and CD8+ T cells were significantly lower than those of normal mature DCs [PF: (1.8±0.5)% vs. (5.2±1.6)% for CD4+ T cells, (2.1±0.6)% vs. (6.5±2.0)%for CD8+ T cells, P<0.01]. These AML supematant-induced DCs could also induce allogeneic CD4+ T cells to differentiate into CD4+CD25high T cells, which had immunophenotyping characteristics of regulatory T cells, i.e. they expressed Foxp3 but not active maker CD69. Conclusion: This study demonstrates that soluble factors secreted by AML cells can inhibit development and functions of DCs. In addition, AML supematant-induced DCs can induce the generation of CD4+CD25high T cells from CD4+T cells, which may be a mechanism of increased prevalence of CD4+CD25high regulatory T cells and immune dysfunction in AML patients.

  15. Categorical action of the extended braid group of affine type A

    OpenAIRE

    Gadbled, Agnes; Thiel, Anne-Laure; Wagner, Emmanuel

    2015-01-01

    Using a quiver algebra of a cyclic quiver, we construct a faithful categorical action of the extended braid group of affine type A on its bounded homotopy category of finitely generated projective modules. The algebra is trigraded and we identify the trigraded dimensions of the space of morphisms of this category with intersection numbers coming from the topological origin of the group.

  16. Universal R-Matrix of Quantum Affine {{gl}(1,1)}

    Science.gov (United States)

    Zhang, Huafeng

    2015-11-01

    The universal R-matrix of the quantum affine superalgebra associated to the Lie superalgebra {gl(1,1)} is realized as the Casimir element of certain Hopf pairing, based on the explicit coproduct formula of all the Drinfeld loop generators.

  17. Artificial Affinity Proteins as Ligands of Immunoglobulins

    Directory of Open Access Journals (Sweden)

    Barbara Mouratou

    2015-01-01

    Full Text Available A number of natural proteins are known to have affinity and specificity for immunoglobulins. Some of them are widely used as reagents for detection or capture applications, such as Protein G and Protein A. However, these natural proteins have a defined spectrum of recognition that may not fit specific needs. With the development of combinatorial protein engineering and selection techniques, it has become possible to design artificial affinity proteins with the desired properties. These proteins, termed alternative scaffold proteins, are most often chosen for their stability, ease of engineering and cost-efficient recombinant production in bacteria. In this review, we focus on alternative scaffold proteins for which immunoglobulin binders have been identified and characterized.

  18. Improved native affinity purification of RNA.

    Science.gov (United States)

    Batey, Robert T; Kieft, Jeffrey S

    2007-08-01

    RNA biochemical or structural studies often require an RNA sample that is chemically pure, and most protocols for its in vitro production use denaturing polyacrylamide gel electrophoresis to achieve this. Unfortunately, many RNAs do not quantitatively refold into an active conformation after denaturation, creating significant problems for downstream characterization or use. In addition, this traditional purification method is not amenable to studies demanding high-throughput RNA production. Recently, we presented the first general method for producing almost any RNA sequence that employs an affinity tag that is removed during the purification process. Because technical difficulties prevented application of this method to many RNAs, we have developed an improved version that utilizes a different activatable ribozyme and affinity tag that are considerably more robust, rapid, and broadly applicable. PMID:17548432

  19. AFFINITY OF LIGNIN PREPARATIONS TOWARDS GENOTOXIC COMPOUNDS

    Directory of Open Access Journals (Sweden)

    Božena Košíková

    2009-02-01

    Full Text Available The carcinogenicity and mutagenicity of chemicals may be modulated by other chemicals, including those prepared by organic synthesis. Consid-ering the several drawbacks of synthetic compounds vis-a-vis the human organism, the lignin biomass component was examined for this purpose. The binding affinity of lignin samples prepared by chemical and biological modification of lignin products derived from chemical wood treatment towards for N-nitrosodiethylamine (NDA was examined. The protective role of the lignin samples against carcinogenesis was tested on a well-known model carcinogen, N-methyl-N´-nitro-N-nitrosoguanidine (MNNG. The observed ability of a series of lignin preparations to reduce alkylation damage of deoxyribonucleic acid (DNA on hamster cells in vitro could be explained by their affinity to bind N-nitrosoamines. The results indicate that lignin has potential to protect living organisms against damaging effects of different genotoxicants.

  20. Phosphopeptide enrichment by immobilized metal affinity chromatography

    DEFF Research Database (Denmark)

    Thingholm, Tine E.; Larsen, Martin R.

    2016-01-01

    binding capacity. After binding, the enriched phosphopeptides are released from the metal ions using alkaline buffers of pH 10–11, EDTA, or phosphate-containing buffers. Here we describe a protocol for IMAC using Fe 3+ for phosphopeptide enrichment. The principles are illustrated on a semi-complex peptide......Immobilized metal affinity chromatography (IMAC) has been the method of choice for phosphopeptide enrichment prior to mass spectrometric analysis for many years and it is still used extensively in many laboratories. Using the affinity of negatively charged phosphate groups towards positively...... charged metal ions such as Fe3+, Ga3+, Al3+, Zr4+, and Ti4+ has made it possible to enrich phosphorylated peptides from peptide samples. However, the selectivity of most of the metal ions is limited, when working with highly complex samples, e.g., whole-cell extracts, resulting in contamination from...

  1. High-affinity neuropeptide Y receptor antagonists.

    OpenAIRE

    Daniels, A J; Matthews, J. E.; Slepetis, R J; Jansen, M; Viveros, O. H.; Tadepalli, A.; Harrington, W; Heyer, D; Landavazo, A; Leban, J J

    1995-01-01

    Neuropeptide Y (NPY) is one of the most abundant peptide transmitters in the mammalian brain. In the periphery it is costored and coreleased with norepinephrine from sympathetic nerve terminals. However, the physiological functions of this peptide remain unclear because of the absence of specific high-affinity receptor antagonists. Three potent NPY receptor antagonists were synthesized and tested for their biological activity in in vitro, ex vivo, and in vivo functional assays. We describe he...

  2. Staircase models from affine Toda field theory

    International Nuclear Information System (INIS)

    The authors propose a class of purely elastic scattering theories generalizing the staircase model of Al. B. Zamolodchikov, based on the affine Toda field theories for simply-laced Lie algebras g = A,D,E at suitable complex values of their coupling constants. Considering their Thermodynamic Bethe Ansatz equations, they give analytic arguments in support of a conjectured renormalization group flow visiting the neighborhood of each Wg minimal model in turn

  3. AFFINE TRANSFORMATION IN RANDOM ITERATED FUNCTION SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    熊勇; 史定华

    2001-01-01

    Random iterated function systems (IFSs) is discussed, which is one of the methods for fractal drawing. A certain figure can be reconstructed by a random IFS. One approach is presented to determine a new random IFS, that the figure reconstructed by the new random IFS is the image of the origin figure reconstructed by old IFS under a given affine transformation. Two particular examples are used to show this approach.

  4. Homogeneous grading affine Toda quantum solitons

    Czech Academy of Sciences Publication Activity Database

    Zuevsky, Alexander

    Vol. 563. Bristol : IOP Science, 2014 - (Burdik, C.; Navratil, O.; Posta, S.), 012036 ISSN 1742-6588. [International Conference on Integrable Systems and Quantum Symmetries (ISQS-22) /22./. Prague (CZ), 26.06.2014-29.06.-2014] Institutional support: RVO:67985840 Keywords : exactly solvable models * conformal and affine Toda systems * quantum groups Subject RIV: BA - General Mathematics http://iopscience.iop.org/1742-6596/563/1/012036

  5. Denominators in cluster algebras of affine type

    OpenAIRE

    Buan, Aslak Bakke; Marsh, Robert J.

    2008-01-01

    The Fomin-Zelevinsky Laurent phenomenon states that every cluster variable in a cluster algebra can be expressed as a Laurent polynomial in the variables lying in an arbitrary initial cluster. We give representation-theoretic formulas for the denominators of cluster variables in cluster algebras of affine type. The formulas are in terms of the dimensions of spaces of homomorphisms in the corresponding cluster category, and hold for any choice of initial cluster.

  6. Thermodynamics. Using Affinities to define reversible processes

    CERN Document Server

    Ritacco, Hernán A

    2016-01-01

    In this article a definition of reversible processes in terms of differences in intensive Thermodynamics properties (Affinities) is proposed. This definition makes it possible to both define reversible processes before introducing the concept of entropy and avoid the circularity problem that follows from the Clausius definition of entropy changes. The convenience of this new definition compared to those commonly found in textbooks is demonstrated with examples.

  7. Neuropeptides as endogenous neuronal growth regulatory factors on serotonergic maturation

    Energy Technology Data Exchange (ETDEWEB)

    Davila-Garcia, M.I.

    1989-01-01

    Products of the proopiomelanocortin molecule as well as leu- and met-enkephalin were tested for their effects on serotonergic neuronal maturation. High affinity uptake of ({sup 3}H)5-HT and morphometrics using immunocytochemistry specific for serotonergic neurons were used to monitor neuronal maturation. Cultured brainstem raphe neurons from 14 day fetuses, in the presence or absence of target tissue, were administered neuropeptides at various concentrations for 1,3 or 5 days in culture. ACTH peptides stimulate neurite length and, with the endorphins, the expression of ({sup 3}H)5-HT uptake by serotonergic fetal neurons cultured alone but had no effect when these neurons were cocultured with hippocampal target cells. A daily dose of leu-enkephalin to these cells inhibited neuronal uptake after 5 days of exposure and decreased neurite cell length in 24 hr cultures. In contrast, a single dose of leu-enkephalin at plating stimulated uptake after 5 days while co-administration of bacitracin inhibited uptake expression. Naloxone reversed the opioid effect and stimulated uptake when administered alone. Desulfated-CCK, which resembles leu-enkephalin, was equally potent as leu-enkephalin in inhibiting uptake.

  8. On constructing purely affine theories with matter

    Science.gov (United States)

    Cervantes-Cota, Jorge L.; Liebscher, D.-E.

    2016-08-01

    We explore ways to obtain the very existence of a space-time metric from an action principle that does not refer to it a priori. Although there are reasons to believe that only a non-local theory can viably achieve this goal, we investigate here local theories that start with Schrödinger's purely affine theory (Schrödinger in Space-time structure. Cambridge UP, Cambridge, 1950), where he gave reasons to set the metric proportional to the Ricci curvature aposteriori. When we leave the context of unified field theory, and we couple the non-gravitational matter using some weak equivalence principle, we can show that the propagation of shock waves does not define a lightcone when the purely affine theory is local and avoids the explicit use of the Ricci tensor in realizing the weak equivalence principle. When the Ricci tensor is substituted for the metric, the equations seem to have only a very limited set of solutions. This backs the conviction that viable purely affine theories have to be non-local.

  9. On constructing purely affine theories with matter

    CERN Document Server

    Cervantes-Cota, Jorge L

    2016-01-01

    We explore ways to obtain the very existence of a space-time metric from an action principle that does not refer to it a priori. Although there are reasons to believe that only a non-local theory can viably achieve this goal, we investigate here local theories that start with Schroedinger's purely affine theory [21], where he gave reasons to set the metric proportional to the Ricci curvature aposteriori. When we leave the context of unified field theory, and we couple the non-gravitational matter using some weak equivalence principle, we can show that the propagation of shock waves does not define a lightcone when the purely affine theory is local and avoids the explicit use of the Ricci tensor in realizing the weak equivalence principle. When the Ricci tensor is substituted for the metric, the equations seem to have only a very limited set of solutions. This backs the conviction that viable purely affine theories have to be non-local.

  10. Overview of affinity biosensors in food analysis.

    Science.gov (United States)

    Patel, Pradip D

    2006-01-01

    The 4 major driving forces that are expected to lead to increased use of affinity biosensors that meet crucial industrial test specifications, e.g., fast, reliable, cost-effective, and use of low-skilled personnel, are (1) strict legislative framework, e.g., recent changes proposed to the European food safety and hygiene legislation, EC No. 178/2002; (2) industrial shift from quality control to quality assurance procedures, e.g., Hazard Analysis Critical Control Point, ensuring effective positioning in the global competitive trade; (3) just-in-time production resulting in 'right' product every time; and (4) consumer demand for safe and wholesome products. The affinity biosensors field has expanded significantly over the past decade, with a projected global biosensors market growth from $6.1 billion in 2004 to $8.2 billion in 2009, representing major industrial sectors (e.g., Pharma, Medicare, and Food). This brief review is targeted to affinity biosensors developed for the food industry and includes research and development leading to biosensors for microbiological and chemical analytes of industrial concern, commercial biosensors products on the market, and examples of future prospects in this diagnostic field. PMID:16792079

  11. A MEMS Dielectric Affinity Glucose Biosensor.

    Science.gov (United States)

    Huang, Xian; Li, Siqi; Davis, Erin; Li, Dachao; Wang, Qian; Lin, Qiao

    2013-06-20

    Continuous glucose monitoring (CGM) sensors based on affinity detection are desirable for long-term and stable glucose management. However, most affinity sensors contain mechanical moving structures and complex design in sensor actuation and signal readout, limiting their reliability in subcutaneously implantable glucose detection. We have previously demonstrated a proof-of-concept dielectric glucose sensor that measured pre-mixed glucose-sensitive polymer solutions at various glucose concentrations. This sensor features simplicity in sensor design, and possesses high specificity and accuracy in glucose detection. However, lack of glucose diffusion passage, this device is unable to fulfill real-time in-vivo monitoring. As a major improvement to this device, we present in this paper a fully implantable MEMS dielectric affinity glucose biosensor that contains a perforated electrode embedded in a suspended diaphragm. This capacitive-based sensor contains no moving parts, and enables glucose diffusion and real-time monitoring. The experimental results indicate that this sensor can detect glucose solutions at physiological concentrations and possesses good reversibility and reliability. This sensor has a time constant to glucose concentration change at approximately 3 min, which is comparable to commercial systems. The sensor has potential applications in fully implantable CGM that require excellent long-term stability and reliability. PMID:24511215

  12. Phosphopeptide Enrichment by Immobilized Metal Affinity Chromatography.

    Science.gov (United States)

    Thingholm, Tine E; Larsen, Martin R

    2016-01-01

    Immobilized metal affinity chromatography (IMAC) has been the method of choice for phosphopeptide enrichment prior to mass spectrometric analysis for many years and it is still used extensively in many laboratories. Using the affinity of negatively charged phosphate groups towards positively charged metal ions such as Fe(3+), Ga(3+), Al(3+), Zr(4+), and Ti(4+) has made it possible to enrich phosphorylated peptides from peptide samples. However, the selectivity of most of the metal ions is limited, when working with highly complex samples, e.g., whole-cell extracts, resulting in contamination from nonspecific binding of non-phosphorylated peptides. This problem is mainly caused by highly acidic peptides that also share high binding affinity towards these metal ions. By lowering the pH of the loading buffer nonspecific binding can be reduced significantly, however with the risk of reducing specific binding capacity. After binding, the enriched phosphopeptides are released from the metal ions using alkaline buffers of pH 10-11, EDTA, or phosphate-containing buffers. Here we describe a protocol for IMAC using Fe(3+) for phosphopeptide enrichment. The principles are illustrated on a semi-complex peptide mixture. PMID:26584922

  13. Fundamentals and application of ordered molecular assemblies to affinity biosensing.

    Science.gov (United States)

    Matharu, Zimple; Bandodkar, Amay Jairaj; Gupta, Vinay; Malhotra, Bansi Dhar

    2012-02-01

    Organization of biomolecules in two/three dimensional assemblies has recently aroused much interest in nanobiotechnology. In this context, the development of techniques for controlling spatial arrangement and orientation of the desired molecules to generate highly-ordered nanostructures in the form of a mono/multi layer is considered highly significant. The studies of monolayer films to date have focused on three distinct methods of preparation: (i) the Langmuir-Blodgett (LB) technique, involving the transfer of a monolayer assembled at the gas-liquid interface; (ii) self-assembly at the liquid-solid interface, based on spontaneous adsorption of desired molecules from a solution directly onto a solid surface; and (iii) Layer-by-layer (LBL) self-assembly at a liquid-solid interface, based on inter-layer electrostatic attractions for fabrication of multilayers. A variety of monolayers have been utilized to fabricate biomolecular electronic devices including biosensors. The composition of a monolayer based matrix has been found to influence the activity(ies) of biomolecule(s). We present comprehensive and critical analysis of ordered molecular assemblies formed by LB and self-assembly with potential applications to affinity biosensing. This critical review on fundamentals and application of ordered molecular assemblies to affinity biosensing is likely to benefit researchers working in this as well as related fields of research (401 references). PMID:22105315

  14. 01-ERD-111 - The Development of Synthetic High Affinity Ligands

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, J; Balhorn, R; Cosman, M; Lightstone, F; Zeller, L

    2004-02-05

    The aim of this project was to develop Synthetic High-Affinity Ligands (SHALs), which bind with high affinity and specificity to proteins of interest for national security and cancer therapy applications. The aim of producing synthetic ligands for sensory devices as an alternative to antibody-based detection assays and therapeutic agents is to overcome the drawbacks associated with antibody-based in next-generation sensors and systems. The focus area of the project was the chemical synthesis of the SHALs. The project concentrated on two different protein targets. (a) The C fragment of tetanus and botulinum toxin, potential biowarfare agents. A SHAL for tetanus or botulinum toxin would be incorporated into a sensory device for the toxins. (b) HLA-DR10, a protein found in high abundance on the surface of Non-Hodgkins Lymphoma. A SHAL specific to a tumor marker, labeled with a radionuclide, would enable the targeted delivery of radiation therapy to metastatic disease. The technical approach used to develop a SHAL for each protein target will be described in more detail below. However, in general, the development of a SHAL requires a combination of computational modeling techniques, modern nuclear magnetic resonance spectroscopy (NMR) and synthetic chemistry.

  15. Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Dimiter S. Dimitrov

    2009-11-01

    Full Text Available Several human monoclonal antibodies (hmAbs and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i antibodies in HIV-1-infected patients (X5 is a CD4i antibody as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and

  16. Quelques remarques sur la notion de modification affine

    OpenAIRE

    Dubouloz, Adrien

    2005-01-01

    in french We construct a global counterpart to the notion of affine modification due to Kaliman and Zaidenberg. This leads to a simple explicit description of the structure of birational affine morphisms between arbitrary quasi-projective varieties.

  17. A multiscale framework for affine invariant pattern recognition and registration

    OpenAIRE

    Rahtu, E. (Esa)

    2007-01-01

    Abstract This thesis presents a multiscale framework for the construction of affine invariant pattern recognition and registration methods. The idea in the introduced approach is to extend the given pattern to a set of affine covariant versions, each carrying slightly different information, and then to apply known affine invariants to each of them separately. The key part of the framework is the construction of the affine covariant set, and this is done by combining several scaled represen...

  18. The purification of affinity-labelled active-site peptides

    International Nuclear Information System (INIS)

    The isolation of the labelled peptide from the protein digest, following the affinity labelling of the active sites of enzymes or antibodies, is described. Single-step affinity chromatography utilises the affinity of the native enzymes or antibody for the ligand used to label the same protein. The labelled peptide is the only one in the digest that displays affinity for the immobilised protein and can be released with eluants that dissociate the protein-ligand complex. (Auth.)

  19. Technology Development Roadmaps - a Systematic Approach to Maturing Needed Technologies

    Energy Technology Data Exchange (ETDEWEB)

    John W. Colllins; Layne Pincock

    2010-07-01

    Abstract. Planning and decision making represent important challenges for all projects. This paper presents the steps needed to assess technical readiness and determine the path forward to mature the technologies required for the Next Generation Nuclear Plant. A Technology Readiness Assessment is used to evaluate the required systems, subsystems, and components (SSC) comprising the desired plant architecture and assess the SSCs against established Technology Readiness Levels (TRLs). A validated TRL baseline is then established for the proposed physical design. Technology Development Roadmaps are generated to define the path forward and focus project research and development and engineering tasks on advancing the technologies to increasing levels of maturity. Tasks include modeling, testing, bench-scale demonstrations, pilot-scale demonstrations, and fully integrated prototype demonstrations. The roadmaps identify precise project objectives and requirements; create a consensus vision of project needs; provide a structured, defensible, decision-based project plan; and, minimize project costs and schedules.

  20. Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications

    OpenAIRE

    Ken-ichiro Matsunaga; Michiko Kimoto; Charlotte Hanson; Michael Sanford; Young, Howard A.; Ichiro Hirao

    2015-01-01

    We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >80% of the remodeled DNA aptamer targeting interferon-γ (K D of 33 pM) survived in human serum at 37 ...

  1. Accumulation and Mixing of Oils in Jinghu Sag of Subei Basin: Constraints from Thermal Maturity Parameters

    Institute of Scientific and Technical Information of China (English)

    HAN Zuo-zhen; CHANG Xiang-chun; GUO Hai-hua; PANG Ling-yun

    2007-01-01

    Oils in Jinghu sag are abundant with high content of polar compounds and have a low ratio of saturate to aromatic hydrocarbons and a high ratio of resin to asphaltene. The gross composition of oils in the Jinghu sag suggests typical immature to low mature characteristics. Some compounds with low thermal stability were identified. Light hydrocarbons, a carbon preference index, an odd even index, n-alkane and hopane maturity parameters show mature features and little differences in the maturity level among oils. Sterane isomerization parameters indicate an immature to low mature status of oil. Transfer of the sedimentary center during sedimentation has led to different thermal histories among subsags and thus generated oils with different maturities. On the basis of source analyses, four migration and accumulation patterns with different maturity can be classified. Combined with available information on mergers of source, reservoir and long distance oil lateral migration, mixing conditions were present in the Jinghu sag. Experimental results indicate that maturity variations are caused by mixtures of hydrocarbons with different maturity.

  2. Duals of Affine Grassmann Codes and Their Relatives

    DEFF Research Database (Denmark)

    Beelen, P.; Ghorpade, S. R.; Hoholdt, T.

    2012-01-01

    Affine Grassmann codes are a variant of generalized Reed-Muller codes and are closely related to Grassmann codes. These codes were introduced in a recent work by Beelen Here, we consider, more generally, affine Grassmann codes of a given level. We explicitly determine the dual of an affine Grassm...

  3. Prediction of SAMPL3 Host-Guest Binding Affinities: Evaluating the Accuracy of Generalized Force-Fields

    OpenAIRE

    Muddana, Hari S.; Gilson, Michael K.

    2012-01-01

    We used the second-generation mining minima method (M2) to compute the binding affinities of the novel host-guest complexes in the SAMPL3 blind prediction challenge. The predictions were in poor agreement with experiment, and we conjectured that much of the error might derive from the force field, CHARMm with Vcharge charges. Repeating the calculations with other generalized force-fields led to no significant improvement, and we observed that the predicted affinities were highly sensitive to ...

  4. Boundaries of Disk-like Self-affine Tiles

    CERN Document Server

    Leung, King-Shun

    2012-01-01

    Let $T:= T(A, {\\mathcal D})$ be a disk-like self-affine tile generated by an integral expanding matrix $A$ and a consecutive collinear digit set ${\\mathcal D}$, and let $f(x)=x^{2}+px+q$ be the characteristic polynomial of $A$. By investigating the neighbors of $T$, we construct a neighbor graph and show that any point on the boundary $\\partial T$ can be identified with a one-sided infinite path of the graph. Also we derive certain equivalent conditions for the pair $(A,{\\mathcal D})$ to be a number system. From the neighbor graph we can deduce a family of graph-directed sets, which gives a second description of $\\partial T$. When $A$ is a similarity, we obtain $\\dim_H (\\partial T)=2\\log \\rho/\\log |q|$ where $\\rho$ is the largest positive zero of the cubic polynomial $x^{3}-(|p|-1)x^{2}-(|q|-|p|)x-|q|$.

  5. Deformation of supersymmetric and conformal quantum mechanics through affine transformations

    Science.gov (United States)

    Spiridonov, Vyacheslav

    1993-01-01

    Affine transformations (dilatations and translations) are used to define a deformation of one-dimensional N = 2 supersymmetric quantum mechanics. Resulting physical systems do not have conserved charges and degeneracies in the spectra. Instead, superpartner Hamiltonians are q-isospectral, i.e. the spectrum of one can be obtained from another (with possible exception of the lowest level) by q(sup 2)-factor scaling. This construction allows easily to rederive a special self-similar potential found by Shabat and to show that for the latter a q-deformed harmonic oscillator algebra of Biedenharn and Macfarlane serves as the spectrum generating algebra. A general class of potentials related to the quantum conformal algebra su(sub q)(1,1) is described. Further possibilities for q-deformation of known solvable potentials are outlined.

  6. Affine generalizations of gravity in the light of modern cosmology

    CERN Document Server

    Filippov, A T

    2010-01-01

    We discuss new models of an `affine' theory of gravity in multidimensional space-times with symmetric connections. We use and develop ideas of Weyl, Eddington, and Einstein, in particular, Einstein's proposal to specify the space - time geometry by use of the Hamilton principle. More specifically, the connection coefficients are determined using a `geometric' Lagrangian that is an arbitrary function of the generalized (non-symmetric) Ricci curvature tensor (and, possibly, of other fundamental tensors) expressed in terms of the connection coefficients regarded as independent variables. Such a theory supplements the standard Einstein gravity with dark energy (the cosmological constant, in the first approximation), a neutral massive (or tachyonic) vector field (vecton), and massive (or tachyonic) scalar fields. These fields couple only to gravity and can generate dark matter and/or inflation. The new field masses (real or imaginary) have a geometric origin and must appear in any concrete model. The concrete choi...

  7. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

    Science.gov (United States)

    Asti, Lorenzo; Uguzzoni, Guido; Marcatili, Paolo; Pagnani, Andrea

    2016-04-01

    The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6), outperforming other sequence- and structure-based models. PMID:27074145

  8. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity

    Science.gov (United States)

    Marcatili, Paolo; Pagnani, Andrea

    2016-01-01

    The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10−6), outperforming other sequence- and structure-based models. PMID:27074145

  9. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

    Directory of Open Access Journals (Sweden)

    Lorenzo Asti

    2016-04-01

    Full Text Available The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6, outperforming other sequence- and structure-based models.

  10. Inhibition of aggregation of amyloid peptides by beta-sheet breaker peptides and their binding affinity.

    Science.gov (United States)

    Viet, Man Hoang; Ngo, Son Tung; Lam, Nguyen Sy; Li, Mai Suan

    2011-06-01

    The effects of beta-sheet breaker peptides KLVFF and LPFFD on the oligomerization of amyloid peptides were studied by all-atom simulations. It was found that LPFFD interferes the aggregation of Aβ(16-22) peptides to a greater extent than does KLVFF. Using the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method, we found that the former binds more strongly to Aβ(16-22). Therefore, by simulations, we have clarified the relationship between aggregation rates and binding affinity: the stronger the ligand binding, the slower the oligomerization process. The binding affinity of pentapeptides to full-length peptide Aβ(1-40) and its mature fibrils has been considered using the Autodock and MM-PBSA methods. The hydrophobic interaction between ligands and receptors plays a more important role for association than does hydrogen bonding. The influence of beta-sheet breaker peptides on the secondary structures of monomer Aβ(1-40) was studied in detail, and it turns out that, in their presence, the total beta-sheet content can be enhanced. However, the aggregation can be slowed because the beta-content is reduced in fibril-prone regions. Both pentapeptides strongly bind to monomer Aβ(1-40), as well as to mature fibrils, but KLVFF displays a lower binding affinity than LPFFD. Our findings are in accord with earlier experiments that both of these peptides can serve as prominent inhibitors. In addition, we predict that LPFFD inhibits/degrades the fibrillogenesis of full-length amyloid peptides better than KLVFF. This is probably related to a difference in their total hydrophobicities in that the higher the hydrophobicity, the lower the inhibitory capacity. The GROMOS96 43a1 force field with explicit water and the force field proposed by Morris et al. (Morris et al. J. Comput. Chem. 1998, 19, 1639 ) were employed for all-atom molecular dynamics simulations and Autodock experiments, respectively. PMID:21563780

  11. High-Affinity Fc Receptor Expression Indicates Relative Immaturity in Human Monocytes.

    Science.gov (United States)

    Clanchy, Felix I L

    2016-05-01

    Within monocyte heterogeneity, subsets represent discrete, well-characterized phenotypes. Although many studies have highlighted differences between subsets, there is evidence that subpopulations represent contiguous stages in a maturational series. As CD14(hi)CD64(hi) monocytes have higher proliferative potential than CD14(hi)CD64(lo) monocytes, the surface marker profile on 4 subsets defined by CD14 and CD64 was measured. The profiles were compared to that of subsets defined by the high-affinity IgE receptor (FcɛRIα), CD16, and CD14; further differences in size, granularity, and buoyancy were measured in subsets delineated by these markers. There was a positive correlation between proliferative monocyte (PM) prevalence and CD64 expression on the classical monocyte subset, and also between PM prevalence and circulating FcɛRIα(+) monocytes. The expression of CD64, the high-affinity IgG receptor, on canonical human monocyte subsets was determined before and after short-term culture, and in response to interleukin (IL)-6, IL-10, macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor and interferon-γ; the influence of these cytokines on monocyte subset transition was also measured. The loss of FcɛRIα expression preceded an increase in CD16 expression in whole blood cultures. These data indicate that high-affinity Fc receptors are expressed on less mature monocytes and that FcɛRIα(+) monocytes are developmentally antecedent to the canonical classical and intermediate monocyte subsets. PMID:26714112

  12. Structure-based rational design of a Toll-like receptor 4 (TLR4 decoy receptor with high binding affinity for a target protein.

    Directory of Open Access Journals (Sweden)

    Jieun Han

    Full Text Available Repeat proteins are increasingly attracting much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural features. Nonetheless, engineering interaction interface and understanding molecular basis for affinity maturation of repeat proteins still remain a challenge. Here, we present a structure-based rational design of a repeat protein with high binding affinity for a target protein. As a model repeat protein, a Toll-like receptor4 (TLR4 decoy receptor composed of leucine-rich repeat (LRR modules was used, and its interaction interface was rationally engineered to increase the binding affinity for myeloid differentiation protein 2 (MD2. Based on the complex crystal structure of the decoy receptor with MD2, we first designed single amino acid substitutions in the decoy receptor, and obtained three variants showing a binding affinity (K(D one-order of magnitude higher than the wild-type decoy receptor. The interacting modes and contributions of individual residues were elucidated by analyzing the crystal structures of the single variants. To further increase the binding affinity, single positive mutations were combined, and two double mutants were shown to have about 3000- and 565-fold higher binding affinities than the wild-type decoy receptor. Molecular dynamics simulations and energetic analysis indicate that an additive effect by two mutations occurring at nearby modules was the major contributor to the remarkable increase in the binding affinities.

  13. Co-evolution of affinity and stability of grafted amyloid-motif domain antibodies.

    Science.gov (United States)

    Julian, Mark C; Lee, Christine C; Tiller, Kathryn E; Rabia, Lilia A; Day, Evan K; Schick, Arthur J; Tessier, Peter M

    2015-10-01

    An attractive approach for designing lead antibody candidates is to mimic natural protein interactions by grafting peptide recognition motifs into the complementarity-determining regions (CDRs). We are using this approach to generate single-domain (VH) antibodies specific for amyloid-forming proteins such as the Alzheimer's Aβ peptide. Here, we use random mutagenesis and yeast surface display to improve the binding affinity of a lead VH domain grafted with Aβ residues 33-42 in CDR3. Interestingly, co-selection for improved Aβ binding and VH display on the surface of yeast yields antibody domains with improved affinity and reduced stability. The highest affinity VH domains were strongly destabilized on the surface of yeast as well as unfolded when isolated as autonomous domains. In contrast, stable VH domains with improved affinity were reliably identified using yeast surface display by replacing the display antibody that recognizes a linear epitope tag at the terminus of both folded and unfolded VH domains with a conformational ligand (Protein A) that recognizes a discontinuous epitope on the framework of folded VH domains. Importantly, we find that selection for improved stability using Protein A without simultaneous co-selection for improved Aβ binding leads to strong enrichment for stabilizing mutations that reduce antigen binding. Our findings highlight the importance of simultaneously optimizing affinity and stability to improve the rapid isolation of well-folded and specific antibody fragments. PMID:26386257

  14. Avoiding degenerate coframes in an affine gauge approach to quantum gravity

    International Nuclear Information System (INIS)

    This report discusses the following concepts on quantum gravity: The affine gauge approach; affine gauge transformations versus active differomorphisms; affine gauge approach to quantum gravity with topology change

  15. CCN1 Regulates Chondrocyte Maturation and Cartilage Development.

    Science.gov (United States)

    Zhang, Yongchun; Sheu, Tzong-Jen; Hoak, Donna; Shen, Jie; Hilton, Matthew J; Zuscik, Michael J; Jonason, Jennifer H; O'Keefe, Regis J

    2016-03-01

    WNT/β-CATENIN signaling is involved in multiple aspects of skeletal development, including chondrocyte differentiation and maturation. Although the functions of β-CATENIN in chondrocytes have been extensively investigated through gain-of-function and loss-of-function mouse models, the precise downstream effectors through which β-CATENIN regulates these processes are not well defined. Here, we report that the matricellular protein, CCN1, is induced by WNT/β-CATENIN signaling in chondrocytes. Specifically, we found that β-CATENIN signaling promotes CCN1 expression in isolated primary sternal chondrocytes and both embryonic and postnatal cartilage. Additionally, we show that, in vitro, CCN1 overexpression promotes chondrocyte maturation, whereas inhibition of endogenous CCN1 function inhibits maturation. To explore the role of CCN1 on cartilage development and homeostasis in vivo, we generated a novel transgenic mouse model for conditional Ccn1 overexpression and show that cartilage-specific CCN1 overexpression leads to chondrodysplasia during development and cartilage degeneration in adult mice. Finally, we demonstrate that CCN1 expression increases in mouse knee joint tissues after meniscal/ligamentous injury (MLI) and in human cartilage after meniscal tear. Collectively, our data suggest that CCN1 is an important regulator of chondrocyte maturation during cartilage development and homeostasis. © 2015 American Society for Bone and Mineral Research. PMID:26363286

  16. Enhancement of Immune Effector Functions by Modulating IgG’s Intrinsic Affinity for Target Antigen

    Science.gov (United States)

    Mazor, Yariv; Yang, Chunning; Borrok, M. Jack; Ayriss, Joanne; Aherne, Karen; Wu, Herren; Dall’Acqua, William F.

    2016-01-01

    Antibody-mediated immune effector functions play an essential role in the anti-tumor efficacy of many therapeutic mAbs. While much of the effort to improve effector potency has focused on augmenting the interaction between the antibody-Fc and activating Fc-receptors expressed on immune cells, the role of antibody binding interactions with the target antigen remains poorly understood. We show that antibody intrinsic affinity to the target antigen clearly influences the extent and efficiency of Fc-mediated effector mechanisms, and report the pivotal role of antibody binding valence on the ability to regulate effector functions. More particularly, we used an array of affinity modulated variants of three different mAbs, anti-CD4, anti-EGFR and anti-HER2 against a panel of target cell lines expressing disparate levels of the target antigen. We found that at saturating antibody concentrations, IgG variants with moderate intrinsic affinities, similar to those generated by the natural humoral immune response, promoted superior effector functions compared to higher affinity antibodies. We hypothesize that at saturating concentrations, effector function correlates most directly with the amount of Fc bound to the cell surface. Thus, high affinity antibodies exhibiting slow off-rates are more likely to interact bivalently with the target cell, occupying two antigen sites with a single Fc. In contrast, antibodies with faster off-rates are likely to dissociate each binding arm more rapidly, resulting in a higher likelihood of monovalent binding. Monovalent binding may in turn increase target cell opsonization and lead to improved recruitment of effector cells. This unpredicted relationship between target affinity and effector function potency suggests a careful examination of antibody design and engineering for the development of next-generation immunotherapeutics. PMID:27322177

  17. On Metrizability of Invariant Affine Connections

    CERN Document Server

    Tanaka, Erico

    2011-01-01

    The metrizability problem for a symmetric affine connection on a manifold, invariant with respect to a group of diffeomorphisms G, is considered. We say that the connection is G-metrizable, if it is expressible as the Levi-Civita connection of a G-invariant metric field. In this paper we analyze the G-metrizability equations for the rotation group G = SO(3), acting canonically on three- and four-dimensional Euclidean spaces. We show that the property of the connection to be SO(3)-invariant allows us to find complete explicit description of all solutions of the SO(3)-metrizability equations.

  18. Quantum affine symmetry in vertex models

    CERN Document Server

    Idzumi, M; Jimbo, M; Miwa, T; Nakashima, T; Tokihiro, T; Idzumi, Makoto; Iohara, Kenji; Jimbo, Michio; Miwa, Tetsuji; Nakashima, Toshiki; Tokihiro, Tetsuji

    1993-01-01

    We study the higher spin anologs of the six vertex model on the basis of its symmetry under the quantum affine algebra $U_q(\\slth)$. Using the method developed recently for the XXZ spin chain, we formulate the space of states, transfer matrix, vacuum, creation/annihilation operators of particles, and local operators, purely in the language of representation theory. We find that, regardless of the level of the representation involved, the particles have spin $1/2$, and that the $n$-particle space has an RSOS-type structure rather than a simple tensor product of the $1$-particle space. This agrees with the picture proposed earlier by Reshetikhin.

  19. Connection between the Affine and conformal Affine Toda models and their Hirota's solution

    International Nuclear Information System (INIS)

    It is shown that the Affine Toda models (AT) constitute a gauge fixed version of the Conformal Affine Toda model (CAT). This result enables one to map every solution of the AT models into an infinite number of solutions of the corresponding CAT models, each one associated to a point of the orbit of the conformal group. The Hirota's τ-function are introduced and soliton solutions for the AT and CAT models associated to SL (r+1) and SP (r) are constructed. (author)

  20. Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding.

    Science.gov (United States)

    Stanfield, Robyn L; Dooley, Helen; Verdino, Petra; Flajnik, Martin F; Wilson, Ian A

    2007-03-23

    Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts with antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop. PMID:17258766

  1. Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity

    Science.gov (United States)

    Matza, Didi; Lantner, Frida; Bogoch, Yoel; Flaishon, Liat; Hershkoviz, Rami; Shachar, Idit

    2002-01-01

    Early stages of B cell development take place in the bone marrow, resulting in formation of immature B cells, which migrate to the spleen for their final differentiation into mature cells. This final maturation step is essential for B cells to become responsive to antigens and to participate in the immune response. Previously, we showed that the MHC class II chaperone, invariant chain (Ii), controls the differentiation of B cells from the immature to the mature stage. In this study, by generating transgenic mice expressing truncated Ii lacking its luminal domain, we could dissect the chaperonin activity of Ii from its role in B cell maturation. We demonstrate in vivo that Ii N-terminal domain is directly involved in the maturation of B cells and is sufficient to promote B cell differentiation. PMID:11867743

  2. Induced Modules for Affine Lie Algebras

    Directory of Open Access Journals (Sweden)

    Vyacheslav Futorny

    2009-03-01

    Full Text Available We study induced modules of nonzero central charge with arbitrary multiplicities over affine Lie algebras. For a given pseudo parabolic subalgebra P of an affine Lie algebra G, our main result establishes the equivalence between a certain category of P-induced G-modules and the category of weight P-modules with injective action of the central element of G. In particular, the induction functor preserves irreducible modules. If P is a parabolic subalgebra with a finite-dimensional Levi factor then it defines a unique pseudo parabolic subalgebra P^{ps}, P subset P^{ps}. The structure of P-induced modules in this case is fully determined by the structure of P^{ps}-induced modules. These results generalize similar reductions in particular cases previously considered by V. Futorny, S. König, V. Mazorchuk [Forum Math. 13 (2001, 641-661], B. Cox [Pacific J. Math. 165 (1994, 269-294] and I. Dimitrov, V. Futorny, I. Penkov [Comm. Math. Phys. 250 (2004, 47-63].

  3. Exploring Fluorous Affinity by Liquid Chromatography.

    Science.gov (United States)

    Catani, Martina; Guzzinati, Roberta; Marchetti, Nicola; Pasti, Luisa; Cavazzini, Alberto

    2015-07-01

    Terms such as "fluorous affinity" and "fluorophilicity" have been used to describe the unique partition and sorption properties often exhibited by highly fluorinated organic compounds, that is molecules rich in sp(3) carbon-fluorine bonds. In this work, we made use of a highly fluorinated stationary phase and a series of benzene derivatives to study the effect of one single perfluorinated carbon on the chromatographic behavior and adsorption properties of molecules. For this purpose, the adsorption equilibria of α,α,α-trifluorotoluene, toluene, and other alkylbenzenes have been studied by means of nonlinear chromatography in a variety of acetonitrile/water eluents. Our results reveal that one single perfluorinated carbon is already enough to induce a drastic change in the adsorption properties of molecules on the perfluorinated stationary phase. In particular, it has been found that adsorption is monolayer if the perfluoroalkyl carbon is present but that, when this unit is missing, molecules arrange as multilayer stack structures. These findings can contribute to the understanding of molecular mechanisms of fluorous affinity. PMID:26047527

  4. Aspects of affine Toda field theory

    International Nuclear Information System (INIS)

    The report is devoted to properties of the affine Toda field theory, the intention being to highlight a selection of curious properties that should be explicable in terms of the underlying group theory but for which in most cases there are no explanation. The motivation for exploring the ideas contained in this report came principally from the recent work of Zamolodchikov concerning the two dimensional Ising model at critical temperature perturbed by a magnetic field. Hollowood and Mansfield pointed out that since Toda field theory is conformal the perturbation considered by Zamolodchikov might well be best regarded as a perturbation of a Toda field theory. This work made it seem plausible that the theory sought by Zamolodchikov was actually affine E8 Toda field theory. However, this connection required an imaginary value of the coupling constant. Investigations here concerning exact S-matrices use a perturbative approach based on real coupling and the results differ in various ways from those thought to correspond to perturbed conformal field theory. A further motivation is to explore the connection between conformal and perturbed conformal field theories in other contexts using similar ideas. (N.K.)

  5. T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy

    Science.gov (United States)

    Zhong, Shi; Malecek, Karolina; Johnson, Laura A.; Yu, Zhiya; Vega-Saenz de Miera, Eleazar; Darvishian, Farbod; McGary, Katelyn; Huang, Kevin; Boyer, Josh; Corse, Emily; Shao, Yongzhao; Rosenberg, Steven A.; Restifo, Nicholas P.; Osman, Iman; Krogsgaard, Michelle

    2013-01-01

    T cells expressing antigen-specific T-cell receptors (TCRs) can mediate effective tumor regression, but they often also are accompanied by autoimmune responses. To determine the TCR affinity threshold defining the optimal balance between effective antitumor activity and autoimmunity in vivo, we used a unique self-antigen system comprising seven human melanoma gp100(209–217)-specific TCRs spanning physiological affinities (1–100 μM). We found that in vitro and in vivo T-cell responses are determined by TCR affinity, except in one case that was compensated by substantial CD8 involvement. Strikingly, we found that T-cell antitumor activity and autoimmunity are closely coupled but plateau at a defined TCR affinity of 10 µM, likely due to diminished contribution of TCR affinity to avidity above the threshold. Together, these results suggest that a relatively low-affinity threshold is necessary for the immune system to avoid self-damage, given the close relationship between antitumor activity and autoimmunity. The low threshold, in turn, indicates that adoptive T-cell therapy treatment strategies using in vitro-generated high-affinity TCRs do not necessarily improve efficacy. PMID:23576742

  6. The Mature Woman and the Community College

    Science.gov (United States)

    Elliot, Jeffrey M.; Mantz, Concetta M.

    1976-01-01

    The factors and motivations contributing to the presence of increasing numbers of mature women in college are examined, and seven proposals are offered, representing an attempt to develop a total community college program which will meet the needs of mature women students. (NHM)

  7. The FMI: Dimensions of Follower Maturity

    Science.gov (United States)

    Moore, Loren I.

    1976-01-01

    The Follower Maturity Index (FMI) is an instrument derived from leadership theory and based on observations of verbal and nonverbal behavior of followers in task groups. Dimensions of follower maturity--achievement, responsibility, experience, activity, dependence, variety, interests, perspective, position, and awareness--are discussed. For…

  8. Quantum Random Number Generators

    OpenAIRE

    Herrero-Collantes, Miguel; Garcia-Escartin, Juan Carlos

    2016-01-01

    Random numbers are a fundamental resource in science and engineering with important applications in simulation and cryptography. The inherent randomness at the core of quantum mechanics makes quantum systems a perfect source of entropy. Quantum random number generation is one of the most mature quantum technologies with many alternative generation methods. We discuss the different technologies in quantum random number generation from the early devices based on radioactive decay to the multipl...

  9. High-affinity FRβ-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity.

    Science.gov (United States)

    Lynn, R C; Feng, Y; Schutsky, K; Poussin, M; Kalota, A; Dimitrov, D S; Powell, D J

    2016-06-01

    Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T-cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here we isolated a high-affinity (HA) folate receptor beta (FRβ)-specific single-chain variable fragment (2.48 nm KD) for optimization of FRβ-redirected CAR T-cell therapy for AML. T cells stably expressing the HA-FRβ CAR exhibited greatly enhanced antitumor activity against FRβ(+) AML in vitro and in vivo compared with a low-affinity FRβ CAR (54.3 nm KD). Using the HA-FRβ immunoglobulin G, FRβ expression was detectable in myeloid-lineage hematopoietic cells; however, expression in CD34(+) hematopoietic stem cells (HSCs) was nearly undetectable. Accordingly, HA-FRβ CAR T cells lysed mature CD14(+) monocytes, while HSC colony formation was unaffected. Because of the potential for elimination of mature myeloid lineage, mRNA CAR electroporation for transient CAR expression was evaluated. mRNA-electroporated HA-FRβ CAR T cells retained effective antitumor activity in vitro and in vivo. Together, our results highlight the importance of antibody affinity in target protein detection and CAR development and suggest that transient delivery of potent HA-FRβ CAR T cells is highly effective against AML and reduces the risk for long-term myeloid toxicity. PMID:26898190

  10. Advanced Stirling Convertor (ASC) Technology Maturation

    Science.gov (United States)

    Wong, Wayne A.; Wilson, Scott; Collins, Josh; Wilson, Kyle

    2016-01-01

    The Advanced Stirling Convertor (ASC) development effort was initiated by NASA Glenn Research Center with contractor Sunpower, Inc., to develop high-efficiency thermal-to-electric power conversion technology for NASA Radioisotope Power Systems (RPSs). Early successful performance demonstrations led to the expansion of the project as well as adoption of the technology by the Department of Energy (DOE) and system integration contractor Lockheed Martin Space Systems Company as part of the Advanced Stirling Radioisotope Generator (ASRG) flight project. The ASRG integrates a pair of ASCs to convert the heat from a pair of General Purpose Heat Source (GPHS) modules into electrical power. The expanded NASA ASC effort included development of several generations of ASC prototypes or engineering units to help prepare the ASC technology and Sunpower for flight implementation. Sunpower later had two parallel contracts allowing the last of the NASA engineering units called ASC-E3 to serve as pathfinders for the ASC-F flight convertors being built for DOE. The ASC-E3 convertors utilized the ASC-F flight specifications and were built using the ASC-F design and process documentation. Shortly after the first ASC-F pair achieved initial operation, due to budget constraints, the DOE ASRG flight development contract was terminated. NASA continues to invest in the development of Stirling RPS technology including continued production of the ASC-E3 convertors, seven of which have been delivered with one additional unit in production. Starting in fiscal year 2015, Stirling Convertor Technology Maturation has been reorganized as an element of the RPS Stirling Cycle Technology Development (SCTD) Project and long-term plans for continued Stirling technology advancement are in reformulation. This paper provides a status on the ASC project, an overview of advancements made in the design and production of the ASC at Sunpower, and a summary of acceptance tests, reliability tests, and tactical

  11. 森林沼泽泥炭不同演化阶段气体碳氢同位素演化特征%Carbon and Hydrogen Isotopic Compositions and Their Evolutions of Gases Generated by Forest Marsh Peat at Different Thermal Maturity Stages

    Institute of Scientific and Technical Information of China (English)

    段毅; 吴应忠; 姚泾利; 刘显阳; 孙涛; 何金先; 徐丽; 夏嘉; 张晓丽

    2013-01-01

    Coalbed methane (CBM) accumulation models include continuous gas accumulation and staged gas accumulation. However, the study on geochemistry characteristics and evaluation index of staged accumulation CBM is inadequate. This study has obtained the carbon and hydrogen isotopic compositions and their evolution laws of methane and ethane generated at different evolution stages by thermal simulation of samples prepared using a forest marsh peat at different temperatures. The data show that the carbon and hydrogen isotopic compositions tend to increase heavy isotope with increasing evolution level of the starting sample. At the same time, it is found that the maturity level of the starting sample influences the carbon isotopic compositions of methane and ethane, while maturity of gases affects their hydrogen isotopic compositions. The relationship between Ro values and the carbon and hydrogen isotopic compositions of gases generated by coal-forming organic matter at different evolution stages as well as the carbon or hydrogen isotopic relationship between methane and ethane are established. These results provide scientific evidence for studying the genesis of CBM generated at different maturity intervals and understanding the geochemistry characteristics of staged accumulation CBM, and they were applied to study on CBM from the southern Qinshui basin, and it is found that it accumulated after Middle Jurassic and is characterized by staged gas accumulation, which indicates that the results of thermal simulation experiments are very important for judging the genesis of natural CBM.%煤层气的成因是石油地质学研究的热点.煤层气聚集存在着“累积聚气”和“阶段聚气”两种形式,对于“阶段聚气”的煤层气成因判识的地球化学研究还很薄弱.通过森林沼泽泥炭在不同温度下制备的样品进行热模拟实验,首次获得了不同演化阶段甲烷、乙烷和二氧化碳的碳、氢同位素组成和演化规

  12. Proteomic changes in mammalian spermatozoa during epididymal maturation

    Institute of Scientific and Technical Information of China (English)

    R. John Aitken; Brett Nixon; Minjie Lin; Adam J. Koppers; Yun H. Lee; Mark A. Baker

    2007-01-01

    Epididymal maturation is associated with the activation of a cAMP-induced tyrosine phosphorylation cascade,which is ultimately associated with the expression of capacitation-dependent sperm functions, such as hyperactivated movement and acrosomal exocytosis. As spermatozoa progress through the epididymis they first acquire the capacity to phosphorylate tyrosine on targets on the principal piece, followed by the midpiece. By the time these cells have reached the cauda epididymidis they can phosphorylate the entire tail from neck to endpiece. This particular pattern of phosphorylation is associated with the ontogeny of fully functional spermatozoa that are capable of fertilizing the oocyte. Proteomic analyses indicate that this change is associated with the phosphorylation of several mitochondrial proteins, creation of a mitochondrial membrane potential and activation of mitochondrial free radical generation. At least in rodent species, activation of sperm mitochondria appears to be a particularly important part of epididymal maturation.

  13. How positive-strand RNA viruses benefit from autophagosome maturation.

    Science.gov (United States)

    Richards, Alexsia L; Jackson, William T

    2013-09-01

    The autophagic degradation pathway is a powerful tool in the host cell arsenal against cytosolic pathogens. Contents trapped inside cytosolic vesicles, termed autophagosomes, are delivered to the lysosome for degradation. In spite of the degradative nature of the pathway, some pathogens are able to subvert autophagy for their benefit. In many cases, these pathogens have developed strategies to induce the autophagic signaling pathway while inhibiting the associated degradation activity. One surprising finding from recent literature is that some viruses do not impede degradation but instead promote the generation of degradative autolysosomes, which are the endpoint compartments of autophagy. Dengue virus, poliovirus, and hepatitis C virus, all positive-strand RNA viruses, utilize the maturation of autophagosomes into acidic and ultimately degradative compartments to promote their replication. While the benefits that each virus reaps from autophagosome maturation are unique, the parallels between the viruses indicate a complex relationship between cytosolic viruses and host cell degradation vesicles. PMID:23760248

  14. The Physiology of Moral Maturity.

    Science.gov (United States)

    Hemming, James

    1991-01-01

    Discusses an evolutionary approach to human morality. Emphasizes the rapid development of brain weight, neural circuits, and synaptic systems during early childhood. Concludes that the human brain has resources for generating responsible, caring behavior but must be nurtured and educated. Urges that moral training in a proper social climate be…

  15. Data Stream Clustering With Affinity Propagation

    KAUST Repository

    Zhang, Xiangliang

    2014-07-09

    Data stream clustering provides insights into the underlying patterns of data flows. This paper focuses on selecting the best representatives from clusters of streaming data. There are two main challenges: how to cluster with the best representatives and how to handle the evolving patterns that are important characteristics of streaming data with dynamic distributions. We employ the Affinity Propagation (AP) algorithm presented in 2007 by Frey and Dueck for the first challenge, as it offers good guarantees of clustering optimality for selecting exemplars. The second challenging problem is solved by change detection. The presented StrAP algorithm combines AP with a statistical change point detection test; the clustering model is rebuilt whenever the test detects a change in the underlying data distribution. Besides the validation on two benchmark data sets, the presented algorithm is validated on a real-world application, monitoring the data flow of jobs submitted to the EGEE grid.

  16. Generalized affine transformation monoids on Galois rings

    OpenAIRE

    Yonglin Cao

    2006-01-01

    Let A be a ring with identity. The generalized affine transformation monoid Gaff(A) is defined as the set of all transformations on A of the form x↦xu+a (for all x∈A), where u,a∈A. We study the algebraic structure of the monoid Gaff(A) on a finite Galois ring A. The following results are obtained: an explicit description of Green's relations on Gaff(A); and an explicit description of the Schützenberger group of every ðÂ’Ÿ-class, which is shown to be isomorphic to the aff...

  17. Gravitational Goldstone fields from affine gauge theory

    CERN Document Server

    Tresguerres, R

    2000-01-01

    In order to facilitate the application of standard renormalization techniques, gravitation should be decribed, if possible, in pure connection formalism, as a Yang-Mills theory of a certain spacetime group, say the Poincare or the affine group. This embodies the translational as well as the linear connection. However, the coframe is not the standard Yang-Mills type gauge field of the translations, since it lacks the inhomogeneous gradient term in the gauge transformations. By explicitly restoring the "hidden" piece responsible for this behavior within the framework of nonlinear realizations, the usual geometrical interpretation of the dynamical theory becomes possible, and in addition one can avoid the metric or coframe degeneracy which would otherwise interfere with the integrations within the path integral. We claim that nonlinear realizations provide a general mathematical scheme clarifying the foundations of gauge theories of spacetime symmetries. When applied to construct the Yang-Mills theory of the aff...

  18. Effectively nonlocal metric-affine gravity

    CERN Document Server

    Golovnev, Alexey; Sandstad, Marit

    2015-01-01

    In metric-affine theories of gravity such as the C-theories, the spacetime connection is associated to a metric that is nontrivially related to the physical metric. In this article, such theories are rewritten in terms of a single metric and it is shown that they can be recast as effectively nonlocal gravity. With some assumptions, known ghost-free theories with non-singular and cosmologically interesting properties may be recovered. Relations between different formulations are analysed at both perturbative and nonperturbative levels taking carefully into account subtleties with boundary conditions in the presence of integral operators in the action, and equivalences between theories related by nonlocal redefinitions of the fields are verified at the level of equations of motion. This suggests a possible geometrical interpretation of nonlocal gravity as an emergent property of non-Riemannian spacetime structure.

  19. Effectively nonlocal metric-affine gravity

    Science.gov (United States)

    Golovnev, Alexey; Koivisto, Tomi; Sandstad, Marit

    2016-03-01

    In metric-affine theories of gravity such as the C-theories, the spacetime connection is associated to a metric that is nontrivially related to the physical metric. In this article, such theories are rewritten in terms of a single metric, and it is shown that they can be recast as effectively nonlocal gravity. With some assumptions, known ghost-free theories with nonsingular and cosmologically interesting properties may be recovered. Relations between different formulations are analyzed at both perturbative and nonperturbative levels, taking carefully into account subtleties with boundary conditions in the presence of integral operators in the action, and equivalences between theories related by nonlocal redefinitions of the fields are verified at the level of equations of motion. This suggests a possible geometrical interpretation of nonlocal gravity as an emergent property of non-Riemannian spacetime structure.

  20. Affine connection form of Regge calculus

    CERN Document Server

    Khatsymovsky, V M

    2015-01-01

    Regge action is represented analogously to how the Palatini action for general relativity (GR) as some functional of the metric and a general connection as independent variables represents the Einstein-Hilbert action. The piecewise flat (or simplicial) spacetime of Regge calculus is equipped with some world coordinates and some piecewise affine metric which is completely defined by the set of edge lengths and the world coordinates of the vertices. The conjugate variables are the general nondegenerate matrices on the 3-simplices which play a role of a general discrete connection. Our previous result on some representation of the Regge calculus action in terms of the local Euclidean (Minkowsky) frame vectors and orthogonal connection matrices as independent variables is somewhat modified for the considered case of the general linear group GL(4,R) of the connection matrices. As a result, we have some action invariant w. r. t. arbitrary change of coordinates of the vertices (and related GL(4,R) transformations in...

  1. Supplier-purchaser relationship assessment maturity model: a study of suppliers from an automotive industry

    OpenAIRE

    Gilberto Zanoni; Edson Pinheiro de Lima; Rosana Mattioda; Sérgio Eduardo Gouvêa da Costa

    2013-01-01

    Operations networks are increasingly demanding in terms of enterprises’ relationships. Strategies and processes integration and capabilities generation between supply chain members become success key factors. This paper proposes a conceptual model for purchaser-supplier relationship maturity level assessment. The maturity levels were developed from a literature review of the stages of the logistics conceptual evolution, from the integration between members of supply chains and from the evolut...

  2. Hecke-Clifford Algebras and Spin Hecke Algebras IV: Odd Double Affine Type

    Directory of Open Access Journals (Sweden)

    Ta Khongsap

    2009-01-01

    Full Text Available We introduce an odd double affine Hecke algebra (DaHa generated by a classical Weyl group $W$ and two skew-polynomial subalgebras of anticommuting generators. This algebra is shown to be Morita equivalent to another new DaHa which are generated by $W$ and two polynomial-Clifford subalgebras. There is yet a third algebra containing a spin Weyl group algebra which is Morita (superequivalent to the above two algebras. We establish the PBW properties and construct Verma-type representations via Dunkl operators for these algebras.

  3. Service Quality and Process Maturity Assessment

    Directory of Open Access Journals (Sweden)

    Serek Radomir

    2013-12-01

    Full Text Available This article deals with service quality and the methods for its measurement and improvements to reach the so called service excellence. Besides older methods such as SERVQUAL and SERPERF, there are also shortly described capability maturity models based on which the own methodology is developed and used for process maturity assessment in organizations providing technical services. This method is equally described and accompanied by examples on pictures. The verification of method functionality is explored on finding a correlation between service employee satisfaction and average process maturity in a service organization. The results seem to be quite promising and open an arena for further studies.

  4. Game Maturity Model for Health Care.

    Science.gov (United States)

    de Boer, Jan C; Adriani, Paul; van Houwelingen, Jan Willem; Geerts, A

    2016-04-01

    This article introduces the Game Maturity Model for the healthcare industry as an extension to the general Game Maturity Model and describes the usage by two case studies of applied health games. The Game Maturity Model for healthcare provides a practical and value-adding method to assess existing games and to determine strategic considerations for application of applied health games. Our forecast is that within 5 years the use and development of applied games will have a role in our daily lives and the way we organize health care that will be similar to the role social media has today. PMID:26859720

  5. Constitutional and Anatomical Characteristics of Mature Women

    Institute of Scientific and Technical Information of China (English)

    Vladimir NNikolenko; DmitryBNikityuk; SvetlanaVKlochkova; AnastasiaABahmet

    2015-01-01

    Objective To identify the constitutional and anatomical peculiarities of constitution of women of mature age.Methods There was completed comprehensive anthropometric and bio-electrical survey of 651 mature women ( relative norm) living in the Moscow region .Results The quantitative distribution of women by somatotypological affiliation was revealed;anthropometric and body component composition in representatives of different somatotypes were defined .Conclusion Thus, the performed study revealed and quantiely character-ised the distribution of women according to their constitutional types in the studied population of mature age women living in Moscow region under the relative norm conditions .

  6. Non-affine displacements in flexible polymer networks

    OpenAIRE

    Basu, Anindita; Wen, Qi; Mao, Xiaoming; Lubensky, T. C.; Janmey, Paul A.; Yodh, A. G.

    2010-01-01

    The validity of the affine assumption in model flexible polymer networks is explored. To this end, the displacements of fluorescent tracer beads embedded in polyacrylamide gels are quantified by confocal microscopy under shear deformation, and the deviations of these displacements from affine responses are recorded. Non-affinity within the gels is quantified as a function of polymer chain density and cross-link concentration. Observations are in qualitative agreement with current theories of ...

  7. Affine Vertex Operator Algebras and Modular Linear Differential Equations

    Science.gov (United States)

    Arike, Yusuke; Kaneko, Masanobu; Nagatomo, Kiyokazu; Sakai, Yuichi

    2016-05-01

    In this paper, we list all affine vertex operator algebras of positive integral levels whose dimensions of spaces of characters are at most 5 and show that a basis of the space of characters of each affine vertex operator algebra in the list gives a fundamental system of solutions of a modular linear differential equation. Further, we determine the dimensions of the spaces of characters of affine vertex operator algebras whose numbers of inequivalent simple modules are not exceeding 20.

  8. Affine Vertex Operator Algebras and Modular Linear Differential Equations

    Science.gov (United States)

    Arike, Yusuke; Kaneko, Masanobu; Nagatomo, Kiyokazu; Sakai, Yuichi

    2016-04-01

    In this paper, we list all affine vertex operator algebras of positive integral levels whose dimensions of spaces of characters are at most 5 and show that a basis of the space of characters of each affine vertex operator algebra in the list gives a fundamental system of solutions of a modular linear differential equation. Further, we determine the dimensions of the spaces of characters of affine vertex operator algebras whose numbers of inequivalent simple modules are not exceeding 20.

  9. Extended affine Weyl groups: Presentation by conjugation via integral collection

    OpenAIRE

    Azam, Saeid; Shahsanaei, Valiollah

    2009-01-01

    We give several necessary and sufficient conditions for the existence of {\\it the presentation by conjugation} for a non-simply laced extended affine Weyl group. We invent a computational tool by which one can determine simply the existence of the presentation by conjugation for an extended affine Weyl group. As an application, we determine the existence of the presentation by conjugation for a large class of extended affine Weyl groups.

  10. Dirac cohomology for the degenerate affine Hecke Clifford algebra

    OpenAIRE

    Chan, Kei Yuen

    2013-01-01

    We define an analogue of the Dirac operator for the degenerate affine Hecke-Clifford algebra. A main result is to relate the central characters of the degenerate affine Hecke-Clifford algebra with the central characters of the Sergeev algebra via Dirac cohomology. The action of the Dirac operator on certain modules is also computed. Results in this paper could be viewed as a projective version of the Dirac cohomology of the degenerate affine Hecke algebra.

  11. DECISION TREE ANALYSIS OF THE PREDICTORS OF INTERNET AFFINITY

    OpenAIRE

    BUBAŠ, Goran; Kliček, Božidar; Hutinski, Željko

    2001-01-01

    A recently developed model of Internet affinity was used for survey design and data collection on variables that have potential influence on affinity for Internet use. A total of 600 Croatian students with access to the Internet at their college participated in this survey. The collected data were used for investigation of the relation between decision tree analysis and regression analysis of predictor variables of Internet affinity. Different predictors were found to influence two distinct c...

  12. Self-affine sets and the continuity of subadditive pressure

    OpenAIRE

    Shmerkin, Pablo

    2013-01-01

    The affinity dimension is a number associated to an iterated function system of affine maps, which is fundamental in the study of the fractal dimensions of self-affine sets. De-Jun Feng and the author recently solved a folklore open problem, by proving that the affinity dimension is a continuous function of the defining maps. The proof also yields the continuity of a topological pressure arising in the study of random matrix products. I survey the definition, motivation and main properties of...

  13. On invariant measures of finite affine type tilings

    OpenAIRE

    Petite, S.

    2004-01-01

    In this paper, we consider tilings of the hyperbolic 2-space, built with a finite number of polygonal tiles, up to affine transformation. To such a tiling T, we associate a space of tilings: the continuous hull Omega(T) on which the affine group acts. This space Omega(T) inherits a solenoid structure whose leaves correspond to the orbits of the affine group. First we prove the finite harmonic measures of this laminated space correspond to finite invariant measures for the affine group action....

  14. Low-complexity piecewise-affine virtual sensors: theory and design

    Science.gov (United States)

    Rubagotti, Matteo; Poggi, Tomaso; Oliveri, Alberto; Pascucci, Carlo Alberto; Bemporad, Alberto; Storace, Marco

    2014-03-01

    This paper is focused on the theoretical development and the hardware implementation of low-complexity piecewise-affine direct virtual sensors for the estimation of unmeasured variables of interest of nonlinear systems. The direct virtual sensor is designed directly from measured inputs and outputs of the system and does not require a dynamical model. The proposed approach allows one to design estimators which mitigate the effect of the so-called 'curse of dimensionality' of simplicial piecewise-affine functions, and can be therefore applied to relatively high-order systems, enjoying convergence and optimality properties. An automatic toolchain is also presented to generate the VHDL code describing the digital circuit implementing the virtual sensor, starting from the set of measured input and output data. The proposed methodology is applied to generate an FPGA implementation of the virtual sensor for the estimation of vehicle lateral velocity, using a hardware-in-the-loop setting.

  15. G-protein coupled estrogen receptor (GPER) inhibits final oocyte maturation in common carp, Cyprinus carpio.

    Science.gov (United States)

    Majumder, Suravi; Das, Sumana; Moulik, Sujata Roy; Mallick, Buddhadev; Pal, Puja; Mukherjee, Dilip

    2015-01-15

    GPR-30, now named as GPER (G protein-coupled estrogen receptor) was first identified as an orphan receptor and subsequently shown to be required for estrogen-mediated signaling in certain cancer cells. Later studies demonstrated that GPER has the characteristics of a high affinity estrogen membrane receptor on Atlantic croaker and zebra fish oocytes and mediates estrogen inhibition of oocyte maturation in these two distantly related teleost. To determine the broad application of these findings to other teleost, expression of GPER mRNA and its involvement in 17β-estradiol mediated inhibition of oocyte maturation in other cyprinid, Cyprinus carpio was investigated. Carp oocytes at pre-vitellogenic, late-vitellogenic and post-vitellogenic stages of development contained GPER mRNA and its transcribed protein with a maximum at late-vitellogenic oocytes. Ovarian follicular cells did not express GPER mRNA. Carp oocytes GPER mRNA was essentially identical to that found in other perciformes and cyprinid fish oocytes. Both spontaneous and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P)-induced oocyte maturation in carp was significantly decreased when they were incubated with either E2, or GPER agonist G-1. On the other hand spontaneous oocyte maturation was significantly increased when carp ovarian follicles were incubated with an aromatase inhibitor, fadrozole, GPER antagonist, G-15 and enzymatic removal of the ovarian follicle cell layers. This increase in oocyte maturation was partially reversed by co-treatment with E2. Consistent with previous findings with human and fish GPR30, E2 treatment in carp oocytes caused increase in cAMP production and simultaneously decrease in oocyte maturation, which was inhibited by the addition of 17,20β-P. The results suggest that E2 and GPER play a critical role in regulating re-entry in to meiotic cell cycle in carp oocytes. PMID:25485460

  16. Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation

    International Nuclear Information System (INIS)

    The expression of transferrin receptors by blood monocytes, human alveolar macrophages, and in vitro matured macrophages was evaluated by immunofluorescence, radioligand binding, and Northern analysis, using the monoclonal anti-human transferrin receptor antibody OKT9, [125I]-labeled human transferrin and a [32P]-labeled human transferrin receptor cDNA probe, respectively. By immunofluorescence, the majority of alveolar macrophages expressed transferrin receptors (86 +/- 3%). The radioligand binding assay demonstrated the affinity constant (K/sub a/) of the alveolar macrophage transferrin receptor was 4.4 +/- 0.7 x 108 M-1, and the number of receptors per cell was 4.4 +/- 1.2 x 104. In marked contrast, transferrin receptors were not present on the surface or in the cytoplasm of blood monocytes, the precursors of the alveolar macrophages. However, when monocytes were cultured in vitro and allowed to mature, > 80% expressed transferrin receptors by day 6, and the receptors could be detected by day 3. Consistent with these observations, a transferrin receptor mRNA with a molecular size of 4.9 kb was demonstrated in alveolar macrophages and in vitro matured macrophages but not in blood monocytes. Thus, although blood monocytes do not express the transferrin receptor gene, it is expressed by mature macrophages, an event that probably occurs relatively early in the process of monocyte differentiation to macrophages

  17. The relation between maturity and sophistication shall be properly dealt with in nuclear power development

    International Nuclear Information System (INIS)

    The paper analyses the advantages and disadvantages of the second generation improved technologies and third generation technologies mainly developed in China in terms of safety and economy. The paper also discusses the maturity of the second generation improved technologies and the sophistication of the third generation technologies respectively. Meanwhile, the paper proposes that the advantage and disadvantage of second generation improved technologies and third generation technologies should be carefully taken into consideration and the relationship between the maturity and sophistication should be properly dealt with in the current stage. A two-step strategy shall be taken as a solution to solve the problem of insufficient capacity of nuclear power, trace and develop the third generation technologies, so as to ensure the sound and fast development of nuclear power. (authors)

  18. Generalized thermal maturity map of Alaska

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This dataset consists of a polygon coverage and associated attribute data derived from the onshore portion of the 1996 "Generalized Thermal Maturity Map of Alaska"...

  19. Pristipomoides filamentosus Size at Maturity Study

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains information used to help determine median size at 50% maturity for the bottomfish species, Pristipomoides filamentosus in the Main Hawaiian...

  20. Elastic Scattering by Deterministic and Random Fractals: Self-Affinity of the Diffraction Spectrum

    OpenAIRE

    Hamburger-Lidar, Daniel A.

    1996-01-01

    The diffraction spectrum of coherent waves scattered from fractal supports is calculated exactly. The fractals considered are of the class generated iteratively by successive dilations and translations, and include generalizations of the Cantor set and Sierpinski carpet as special cases. Also randomized versions of these fractals are treated. The general result is that the diffraction intensities obey a strict recursion relation, and become self-affine in the limit of large iteration number, ...

  1. Distribution pattern, zoogeographic similarities and affinities of montane herpetofauna of Southern Eastern Ghats, peninsular India

    OpenAIRE

    Ganesh, Sumaithangi Rajagopalan; Arumugam, Munusamy

    2016-01-01

    We examined the distribution pattern, across-site similarities and zoogeographic affinities of amphibians and reptiles in the montane zones (> 900 m a.s.l.) of the Southern Eastern Ghats mountains in peninsular India. We deployed long-term field surveys in four select massifs namely Jawadi, Shevaroys, Kolli and Sirumalai and generated herpetofaunal species lists. Based solely on our species occurrence data, we identified taxa that characterise sites, site-pairs and site-clusters. We quantifie...

  2. Positive electron affinity of interfacial region in Polyethylene-MgO nanocomposite dielectric

    OpenAIRE

    Kubyshkina, Elena; Unge, Mikael; Jonsson, B. L. G.

    2016-01-01

    Polymer-based nanocomposite dielectrics are expected to become essential in future generations of high voltage electrical insulation. However, the physics behind their performance is not yet understood. Here we investigate electronic properties of the interfacial area in magnesium oxide-polyethylene nanocomposite. We use density functional theory to demonstrate positive electron affinity for MgO (100) and hydroxylated MgO (111) interfaces with polyethylene. We evaluate the role of silicon-bas...

  3. Metal-conjugated affinity labels: A new concept to create enantioselective artificial metalloenzymes

    KAUST Repository

    Reiner, Thomas

    2013-02-20

    How to train a protein: Metal-conjugated affinity labels were used to selectively position catalytically active metal centers in the binding pocket of proteases. The resulting artificial metalloenzymes achieve up to 82% e.r. in the hydrogenation of ketones. The modular setup enables a rapid generation of artificial metalloenzyme libraries, which can be adapted to a broad range of catalytic conditions. 2013 The Authors.

  4. A STUDY ON CONTROL AFFINE SYSTEMS WITH POSITIVE HOMOGENEOUS COST AND NO CONSTANT RANK OF DISTRIBUTION*

    OpenAIRE

    Assoc. Prof. Popescu Liviu Ph.D

    2010-01-01

    The paper deals with the study of a drift less control affine system with positive homogeneous cost of Randers type in the case of bracket generating distribution of no constant rank. We use the Pontryagin Maximum Principle in order to find the general solution. In the particular case of quadratic cost the optimal trajectories of the distributional system are the geodesics of the so called sub-Riemannian geometry.

  5. Maturational Changes in Dentin Mineral Properties

    OpenAIRE

    Verdelis, K.; Lukashova, L.; Wright, J. T.; Mendelsohn, R; Peterson, M. G. E.; Doty, S.; Boskey, A. L.

    2007-01-01

    In this study the changes in properties of the maturing mantle and circumpulpal dentin were quantitatively analyzed. Sections from six fetal bovine undecalcified incisors were used. Regions of mantle and circumpulpal dentin of sequential maturation stages were identified on spectroscopic images acquired by Fourier Transform Infrared Imaging. Spectroscopic parameters corresponding to mineral properties at these stages were analyzed and reported as a function of distance from the cervix of the ...

  6. Obesity accelerates secondary sexual maturity in girls

    OpenAIRE

    Meiriani Sari; Endy Paryanto Prawirohartono; Madarina Julia

    2012-01-01

    Background Worldwide incidence of obesity in children is increasing. Obesity may have many health effects including advancement of sexual maturity. Objective The aim of this study was to assess the timing of secondary sexual maturation in obese vs. non-obese girls. Methods Subjects were 105 obese and 105 non-obese girls, aged 7 to 8 years who had not entered puberty. Breast and pubic hair growth, secondary sexual characteristics, were assessed at baseline and every 4 months for two ye...

  7. SKIN DENDRITIC CELLS: ACTIVATION, MATURATION AND MIGRATION

    OpenAIRE

    Eaton, Laura

    2012-01-01

    Langerhans’ cells (LC) are the dendritic cells (DC) of the epidermis and, as sentinels of the immune system, act as a bridge between the innate and adaptive immune responses. When LC, and other DC, recognise an antigen or pathogen they mature and are stimulated to migrate to the lymph nodes, where they orchestrate immune responses. Pathogen derived toll-like receptor (TLR) ligands, and chemical allergens, are recognised as being potentially harmful and stimulate LC to mobilise and mature. Cyt...

  8. General smile asymptotics with bounded maturity

    OpenAIRE

    Francesco Caravenna; Jacopo Corbetta

    2014-01-01

    We provide explicit conditions on the distribution of risk-neutral log-returns which yield sharp asymptotic estimates on the implied volatility smile. We allow for a variety of asymptotic regimes, including both small maturity (with arbitrary strike) and extreme strike (with arbitrary bounded maturity), extending previous work of Benaim and Friz [Math. Finance 19 (2009), 1-12]. We present applications to popular models, including Carr-Wu finite moment logstable model, Merton's jump diffusion ...

  9. Two-parameter quantum affine algebra Ur,s(sln-circumflex), Drinfeld realization and quantum affine Lyndon basis

    International Nuclear Information System (INIS)

    We further find the defining structure of a two-parameter quantum affine algebra Ur,s(sln-circumflex) (n > 2) in the sense of Benkart-Witherspoon [BW1] after the work of [BGH1], [HS] and [BH], which turns out to be a Drinfeld double. Of more importance for the 'affine' cases is that we work out the compatible two-parameter version of the Drinfeld realization as a quantum affinization of Ur,s(sln) and establish the Drinfeld isomorphism Theorem in the two-parameter setting via developing a new remarkable combinatorial approach - quantum 'affine' Lyndon basis with an explicit valid algorithm, based on the Drinfeld realization. (author)

  10. Mature students' perspectives of studying radiography

    International Nuclear Information System (INIS)

    The study set out to explore the experiences of all final year mature students on a diagnostic radiography course, in one United Kingdom University. The aims were to identify any difficulties they may have had and to make recommendations to improve mature students' learning experiences with the hope of lowering attrition rates in this group. A qualitative study involving one-to-one audio recorded interviews was utilised. Analysis of the transcripts of interviews suggested that the group believed that their maturity and previous experiences helped them in the clinical environment and put them in a good position, when asked, to counsel younger students. However for some of the mature students these experiential skills did not extend fully into seeking appropriate support for themselves. The mature students were found to be highly motivated but there was a conflict between balancing clinical and academic aspects of studying as well as balancing studying with home life. The group was found to be unprepared for the volume of academic work and its detrimental effect on family life as they sacrificed other aspects of their lives in order to complete the course. It is recommended that forewarning and forearming prospective mature students be considered by radiography education providers. Setting up and utilising an on-line forum providing a 24/7 peer support environment would aid in coping with academic, clinical or personal problems

  11. Structural Change in the Dynein Stalk Region Associated with Two Different Affinities for the Microtubule.

    Science.gov (United States)

    Nishikawa, Yosuke; Inatomi, Momoko; Iwasaki, Haruka; Kurisu, Genji

    2016-05-01

    Dynein is a large microtubule-based motor complex that requires tight coupling of intra-molecular ATP hydrolysis with the generation of mechanical force and track-binding activity. However, the microtubule-binding domain is structurally separated by about 15nm from the nucleotide-binding sites by a coiled-coil stalk. Thus, long-range two-way communication is necessary for coordination between the catalytic cycle of ATP hydrolysis and dynein's track-binding affinities. To investigate the structural changes that occur in the dynein stalk region to produce two different microtubule affinities, here we improve the resolution limit of the previously reported structure of the entire stalk region and we investigate structural changes in the dynein stalk and strut/buttress regions by comparing currently available X-ray structures. In the light of recent crystal structures, the basis of the transition from the low-affinity to the high-affinity coiled-coil registry is discussed. A concerted movement model previously reported by Carter and Vale is modified more specifically, and we proposed it as the open zipper model. PMID:26585405

  12. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII. PMID:23244324

  13. PolyCheck: Dynamic Verification of Iteration Space Transformations on Affine Programs

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Wenlei; Krishnamoorthy, Sriram; Pouchet, Louis-noel; Rastello, Fabrice; Sadayappan, Ponnuswamy

    2016-01-11

    High-level compiler transformations, especially loop transformations, are widely recognized as critical optimizations to restructure programs to improve data locality and expose parallelism. Guaranteeing the correctness of program transformations is essential, and to date three main approaches have been developed: proof of equivalence of affine programs, matching the execution traces of programs, and checking bit-by-bit equivalence of the outputs of the programs. Each technique suffers from limitations in either the kind of transformations supported, space complexity, or the sensitivity to the testing dataset. In this paper, we take a novel approach addressing all three limitations to provide an automatic bug checker to verify any iteration reordering transformations on affine programs, including non-affine transformations, with space consumption proportional to the original program data, and robust to arbitrary datasets of a given size. We achieve this by exploiting the structure of affine program control- and data-flow to generate at compile-time lightweight checker code to be executed within the transformed program. Experimental results assess the correctness and effectiveness of our method, and its increased coverage over previous approaches.

  14. Comparative Proteomic Analysis of Arabidopsis Mature Pollen and Germinated Pollen

    Institute of Scientific and Technical Information of China (English)

    Junjie Zou; Lianfen Song; Wenzheng Zhang; Yi Wang; Songlin Ruan; Wei-Hua Wu

    2009-01-01

    Proteomic analysis was applied to generating the map of Arabidopsis mature pollen proteins and analyzing the differentially expressed proteins that are potentially involved in the regulation of Arabidopsis pollen germination. By applying 2-D electrophoresis and silver staining, we resolved 499 and 494 protein spots from protein samples extracted from pollen grains and pollen tubes, respectively. Using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry method, we identified 189 distinct proteins from 213 protein spots expressed in mature pollen or pollen tubes, and 75 new identified proteins that had not been reported before in research into the Arabidopsis pollen proteome. Comparative analysis revealed that 40 protein spots exhibit reproducible significant changes between mature pollen and pollen tubes. And 21 proteins from 17 downregulated and six upregulated protein spots were identified. Functional category analysis indicated that these differentially expressed proteins mainly involved in signaling, cellular structure, transport, defense/stress responses, transcription, metabolism, and energy production. The patterns of changes at protein level suggested the important roles for energy metabolism-related proteins in pollen tube growth, accompanied by the activation of the stress response pathway and modifications to the cell wall.

  15. The Influence of Ouabain on Human Dendritic Cells Maturation

    Directory of Open Access Journals (Sweden)

    C. R. Nascimento

    2014-01-01

    Full Text Available Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua. Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate DC maturation under Ouabain influence. To generate immature DCs, human monocytes were cultured with IL-4 and GM-CSF (5 days. To investigate Ouabain role on DC activation, DCs were stimulated with TNF-α for 48 h in the presence or absence of Ouabain. TNF-induced CD83 expression and IL-12 production were abolished in DCs incubated with 100 nM Ouabain, though DC functional capacity concerning lymphocyte activation remained unaltered. Nevertheless, TNF-α-induced antigen capture downregulation, another maturation marker, occurred even in the presence of Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80 expression was maintained. Collectively, our results suggest that DCs respond to Ouabain maturating into a distinct category, possibly contributing to the balance between immunity and tolerance.

  16. Maturity acceleration of Italian dried sausage by Staphylococcus carnosus - Relationship between maturity and flavor compounds

    DEFF Research Database (Denmark)

    Stahnke, Louise Heller; Holck, A.; Jensen, Anni;

    2002-01-01

    The mature flavor of Salame Milano, an Italian dried sausage, was increased in two ways: by increasing maturation time or with a strain of Staphylococcus carnosus. The sensory and volatile profiles of the sausages were determined and the data analyzed by analysis of variance and chemometrics. Sau......, and valine, or from microbial beta-oxidation of fatty acids. Also, sulfur compounds arising from added garlic correlated positively with mature flavor....

  17. Two-parameter quantum affine algebra of type G2(1), Drinfeld realization and vertex representation

    International Nuclear Information System (INIS)

    In this paper, we define the two-parameter quantum affine algebra for type G2(1) and give the (r, s)-Drinfeld realization of Ur,s(G2(1)), as well as establish and prove its Drinfeld isomorphism. We construct and verify explicitly the level-one vertex representation of two-parameter quantum affine algebra Ur,s(G2(1)), which also supports an evidence in nontwisted type G2(1) for the uniform defining approach via the two-parameter τ-invariant generating functions proposed in Hu and Zhang [Generating functions with τ-invariance and vertex representations of two-parameter quantum affine algebras Ur,s(g^): Simply laced cases e-print http://arxiv.org/abs/1401.4925

  18. Development and maturation of norovirus antibodies in childhood.

    Science.gov (United States)

    Blazevic, Vesna; Malm, Maria; Honkanen, Hanna; Knip, Mikael; Hyöty, Heikki; Vesikari, Timo

    2016-04-01

    The burden of norovirus (NoV) gastroenteritis is substantial in young children. Maternal antibodies are thought to protect a child from NoV infection in early infancy but subsequent development of NoV-specific protective immunity in children is still largely unexplored. We have determined NoV-specific antibody seroconversion to GII.4 virus-like particles as an indicator of NoV infection in two children prospectively followed from birth to eight years of age. Blocking activity and affinity maturation of maternal and serum IgG antibodies were evaluated. Our results show that multiple infections occur in children up to eight years of age. The titer, blocking activity and avidity of maternal antibodies determined susceptibility of an infant to NoV infection. NoV GII.4-specific antibodies with high blocking potential and avidity were developed at two to three years of age and were retained throughout the follow-up. Subsequent NoV infections may have contributed to the duration of protective NoV-specific immune responses that lasted for several years. This study adds to current understanding of the duration of passive protection by maternal antibodies and the duration and quality of acquired immunity following primary and subsequent NoV infections in infants and young children, who are the main target group for NoV vaccine development. PMID:26724451

  19. National Assessment of Oil and Gas Project - San Joaquin Basin Province (010) Pod(s) of Mature Source Rock

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The Pod (or pods) of Mature Source Rock is a critical element of the Total Petroleum System and incorporates all source rocks that potentially have generated...

  20. National Assessment of Oil and Gas Project - Uinta-Piceance Province (020) Pod(s) of Mature Source Rock

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The Pod (or pods) of Mature Source Rock is a critical element of the Total Petroleum System and incorporates all source rocks that potentially have generated...

  1. National Assessment of Oil and Gas Project - Florida Peninsula Province (050) Pod(s) of Mature Source Rock

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The Pod (or pods) of Mature Source Rock is a critical element of the Total Petroleum System and incorporates all source rocks that potentially have generated...

  2. Affinity of guanosine derivatives for polycytidylate revisited

    Science.gov (United States)

    Kanavarioti, A.; Hurley, T. B.; Baird, E. E.

    1995-01-01

    Evidence is presented for complexation of guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) with polycytidylate (poly(C)) at pH 8.0 and 23 degrees C in the presence of 1.0 M NaCl2 and 0.2 M MgCl2 in water. The association of 2-MeImpG with poly(C) was investigated using UV-vis spectroscopy as well as by monitoring the kinetics of the nucleophilic substitution reaction of the imidazole moiety by amines. The results of both methods are consistent with moderately strong poly(C) 2-MeImpG complexation and the spectrophotometric measurements allowed the construction of a binding isotherm with a concentration of 2-MeImpG equal to 5.55 +/- 0.15 mM at half occupancy. UV spectroscopy was employed to establish the binding of other guanosine derivatives on poly(C). These derivatives are guanosine 5'-monophosphate (5'GMP), guanosine 5'-monophosphate imidazolide (ImpG), and guanosine 5'-monophosphate morpholidate (morpG). Within experimental error these guanosine derivatives exhibit the same affinity for poly(C) as 2-MeImpG.

  3. Asymptotic weight and maturing rate in mice selected for body conformation

    Directory of Open Access Journals (Sweden)

    Di Masso Ricardo J.

    2000-01-01

    Full Text Available Growth patterns of four lines of mice selected for body conformation were analyzed with the logistic function, in order to provide baseline information about the relationship between asymptotic weight and maturing rate of body weight. Two lines were divergently selected favoring the phenotypic correlation between body weight and tail length (agonistic selection: CBi+, high body weight and long tail; CBi-, low body weight and short tail, whereas the other two lines were generated by a disruptive selection performed against the correlation between the aforementioned traits (antagonistic selection: CBi/C, high body weight and short tail; CBi/L, low body weight and long tail. The logistic parameters A (asymptotic weight and k (maturing rate behaved in CBi/C and CBi- mice and in CBi+ females as expected in terms of the negative genetic relationship between mature size and earliness of maturing. An altered growth pattern was found in CBi/L mice and in CBi+ males, because in the former genotype, selected for low body weight, the time taken to mature increased, whereas in the latter, selected for high body weight, there was a non-significant increase in the same trait. In accordance with the selective criterion, different sources of genetic variation for body weight could be exploited: one inversely associated with earliness of maturing (agonistic selection, and the other independent of maturing rate (antagonistic selection, showing that genetic variation of A is partly independent of k.

  4. Synthesis of tetracycline analogs and their bone affinities

    Institute of Scientific and Technical Information of China (English)

    Wen Cai Huang; Hu Zheng; Ling Ling Weng

    2008-01-01

    Tetracycline analogs were designed and synthesized and their bone affinities were tested on hydroxyapatite. The results showedthat the carbonyl-amide-enol structure in A ring and phenol-ketone structure in BCD ring may be responsible for tetracycline's highbone affinity and either A ring or BCD ring has a planar conformation is essential.

  5. Self-affine roughness influence on redox reaction charge admittance

    NARCIS (Netherlands)

    Palasantzas, G

    2005-01-01

    In this work we investigate the influence of self-affine electrode roughness on the admittance of redox reactions during facile charge transfer kinetics. The self-affine roughness is characterized by the rms roughness amplitude w, the correlation length xi and the roughness exponent H (0

  6. Striving for Empathy: Affinities, Alliances and Peer Sexuality Educators

    Science.gov (United States)

    Fields, Jessica; Copp, Martha

    2015-01-01

    Peer sexuality educators' accounts of their work reveal two approaches to empathy with their students: affinity and alliance. "Affinity-based empathy" rests on the idea that the more commonalities sexuality educators and students share (or perceive they share), the more they will be able to empathise with one another, while…

  7. Tending to Change: Toward a Situated Model of Affinity Spaces

    Science.gov (United States)

    Bommarito, Dan

    2014-01-01

    The concept of affinity spaces, a theoretical construct used to analyze literate activity from a spatial perspective, has gained popularity among scholars of literacy studies and, particularly, video-game studies. This article seeks to expand current notions of affinity spaces by identifying key assumptions that have limited researchers'…

  8. Maturity acceleration of Italian dried sausage by Staphylococcus carnosus - Relationship between maturity and flavor compounds

    DEFF Research Database (Denmark)

    Stahnke, Louise Heller; Holck, A.; Jensen, Anni; Nilsen, A.; Zanardi, E.

    2002-01-01

    The mature flavor of Salame Milano, an Italian dried sausage, was increased in two ways: by increasing maturation time or with a strain of Staphylococcus carnosus. The sensory and volatile profiles of the sausages were determined and the data analyzed by analysis of variance and chemometrics....... Sausages with S. carnosus 833 matured more than 2 wk faster than control sausages. Maturity correlated significantly with higher amounts of branched-chain aldehydes and alcohols and both branched- and straight-chain methyl ketones-compounds arising from the breakdown of the amino acids leucine, isoleucine...

  9. IMPLEMENTASI ENKRIPSI DEKRIPSI ALGORITMA AFFINE CIPHER BERBASIS ANDROID

    Directory of Open Access Journals (Sweden)

    Sasono Wibowo

    2014-11-01

    Full Text Available Perkembangan Teknologi Informasi yang cukup pesat khususnya dalam bidang komunikasi menjadikan komunikasi sangat mudah namun dalam implementasinya perlu adanya keamanan tentang informasi yang disampaikan. Dalam komunikasi antar orang pasti memiliki pembicaraan informasi yang bersifat privat atau orang lain tidak boleh tahu tentang pembicaraan yang terjadi. Diperlukannya keamanan untuk menjaga kerahasiaan informasi pada saat komunikasi. Masyarakat lebih sering menggunakan komunikasi dengan telepon seluler karena dinilai mudah dibawa dan tidak repot menggunakannya. Kriptografi yang biasa dikenal sebagai ilmu yang mempelajari bagaimana cara menyembunyikan pesan bisa diterapkan dalam aplikasi pada telepon seluler sebagai contoh smartphone android. Dengan mengimplementasikan algoritma affine cipher maka aplikasi yang akan dibuat bisa mengubah isi pesan yang ada dan dapat mengamankan informasi yang ada. Algoritma affine cipher merupakan perkembangan dari algoritma caesar dimana algoritma affine cipher menggunakan dua kunci. Dengan mengimplementasikan algoritma affine cipher ke dalam android maka diharapkan kita bisa menyimpan informasi dari siapapun tanpa terbaca. Kata Kunci : Kriptografi, Affine Cipher, android, Implementasi, Informasi

  10. Ablation of the cellular prion protein, PrPC, specifically on follicular dendritic cells has no effect on their maturation or function.

    Science.gov (United States)

    McCulloch, Laura; Brown, Karen L; Mabbott, Neil A

    2013-03-01

    Follicular dendritic cells (FDC) are situated in the primary follicles of lymphoid tissues where they maintain the structural integrity of the B-lymphocyte follicle, and help to drive immunoglobulin class-switch recombination, somatic hypermutation and affinity maturation during the germinal centre response. FDC can also provide a reservoir for pathogens that infect germinal centres including HIV and prions. FDC express high levels of the normal cellular form of the prion protein (PrP(C) ), which makes them susceptible to prion infection. The function of PrP(C) is uncertain and it is not known why FDC require such high levels of expression of a protein that is found mainly on cells of the central nervous system. In this study, the function of FDC was assessed in mice that had PrP(C) ablated specifically in their FDC. In mice with FDC-specific PrP(C) ablation, our analysis revealed no observable deficits in lymphoid follicle microarchitecture and FDC status. No effects on FDC ability to trap immune complexes or drive antigen-specific antibody responses and affinity maturation in B lymphocytes were observed. These data clearly demonstrate that PrP(C) expression is dispensable for the functional maturation of FDC and their ability to maintain antigen-specific antibody responses and affinity maturation. PMID:23121447

  11. Chasing polys: Interdisciplinary affinity and its connection to physics identity

    Science.gov (United States)

    Scott, Tyler D.

    This research is based on two motivations that merge by means of the frameworks of interdisciplinary affinity and physics identity. First, a goal of education is to develop interdisciplinary abilities in students' thinking and work. But an often ignored factor is students interests and beliefs about being interdisciplinary. Thus, this work develops and uses a framework called interdisciplinary affinity. It encompasses students interests in making connections across disciplines and their beliefs about their abilities to make those connections. The second motivation of this research is to better understand how to engage more students with physics. Physics identity describes how a student sees themselves in relation to physics. By understanding how physics identity is developed, researchers and educators can identify factors that increase interest and engagement in physics classrooms. Therefore, physics identity was used in conjunction with interdisciplinary affinity. Using a mixed methods approach, this research used quantitative data to identify the relationships interdisciplinary affinity has with physics identity and the physics classroom. These connections were explored in more detail using a case study of three students in a high school physics class. Results showed significant and positive relationships between interdisciplinary affinity and physics identity, including the individual interest and recognition components of identity. It also identified characteristics of physics classrooms that had a significant, positive relationship with interdisciplinary affinity. The qualitative case study highlighted the importance of student interest to the relationship between interdisciplinary affinity and physics identity. It also identified interest and mastery orientation as key to understanding the link between interdisciplinary affinity and the physics classroom. These results are a positive sign that by understanding interdisciplinary affinity and physics identity

  12. Electrochemical immobilization of Fluorescent labelled probe molecules on a FTO surface for affinity detection based on photo-excited current

    Energy Technology Data Exchange (ETDEWEB)

    Haruyama, Tetsuya; Wakabayashi, Ryo; Cho, Takeshi; Matsuyama, Sho-taro, E-mail: haruyama@life.kyutech.as.jp [Kyushu Institute of Technology, Department of Biological Functions and Engineering, Kitakyushu Science and Research Park, Hibikino, Kitakyushu, Fukuoka 808-0196 (Japan)

    2011-10-29

    Photo-excited current can be generated at a molecular interface between a photo-excited molecules and a semi-conductive material in appropriate condition. The system has been recognized for promoting photo-energy devices such as an organic dye sensitized solar-cell. The photo-current generated reactions are totally dependent on the interfacial energy reactions, which are in a highly fluctuated interfacial environment. The authors investigated the photo-excited current reaction to develop a smart affinity detection method. However, in order to perform both an affinity reaction and a photo-excited current reaction at a molecular interface, ordered fabrications of the functional (affinity, photo-excitation, etc.) molecules layer on a semi-conductive surface is required. In the present research, we would like to present the fabrication and functional performance of photo-excited current-based affinity assay device and its application for detection of endocrine disrupting chemicals. On the FTO surface, fluorescent pigment labelled affinity peptide was immobilized through the EC tag (electrochemical-tag) method. The modified FTO produced a current when it was irradiated with diode laser light. However, the photo current decreased drastically when estrogen (ES) coexisted in the reaction solution. In this case, immobilized affinity probe molecules formed a complex with ES and estrogen receptor (ER). The result strongly suggests that the photo-excited current transduction between probe molecule-labelled cyanine pigment and the FTO surface was partly inhibited by a complex that formed at the affinity oligo-peptide region in a probe molecule on the FTO electrode. The bound bulky complex may act as an impediment to perform smooth transduction of photo-excited current in the molecular interface. The present system is new type of photo-reaction-based analysis. This system can be used to perform simple high-sensitive homogeneous assays.

  13. Genetic analysis of maturity and flowering characteristics in maize (Zea mays L.)

    Institute of Scientific and Technical Information of China (English)

    Hassan Sher; Muhammad Iqbal; Kiramat Khan; Muhammad yasir; Hameed-ur-Rahman

    2012-01-01

    Objective: To elucidate the pattern of inheritance and determine the relative magnitude of various genetic effects for maturity and flowering attributes in subtropical maize. Methods:Four white grain maize inbred lines from flint group of corn, two with late maturity and two with early maturity, were used. These contrasting inbred lines were crossed to form four crosses. Six generations (P1, P2, F1, F2, BC1, and BC2) were developed for each individual cross. These were evaluated in triplicate trial for two consecutive years. Results: Both dominance gene action and epistatic interaction played major role in governing inheritance of days to pollen shedding, 50% silking, anthesis silking interval and maturity. Conclusions: Preponderance of dominance gene action for these traits indicated their usefulness in hybrid programs of subtropical maize.

  14. Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent

    International Nuclear Information System (INIS)

    In spite of recent advances in bone cellular and molecular biology, there is still a poor correlation between these parameters and data obtained from bone scintigraphy. Diphosphonate derivatives radiolabelled with technetium-99m (Tc-BPs) have long been recognised as bone-seeking agents with an affinity for areas of active mineralisation. However, during clinical trials with a pH-sensitive tumour agent, the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] showed a noticeable osteotropic character only in bone pathologies (bone metastases, Paget's diseases) and lacked accumulation in normal mature bone. To decipher the osteotropic character of Tc(V)-DMS, a study at the cellular level was considered necessary. Moreover, to learn more about the role of Tc bone agents, acid-base regulation by bone tissue or cells was studied. First, biological parameters in body fluid were measured under systemic acidosis, induced by glucose administration, in normal and Ehrlich ascites tumour (EAT)-bearing mice. Then, in vivo biodistribution studies using Tc(V)-DMS or a conventional Tc-BP agent were carried out. The effect of glucose-mediated acidification on the skeletal distribution of the Tc agents in the mice provided valuable hints regarding the differential mediation of bone cells in skeletal tissue affinity for the agents. Thereafter, in vitro studies on osteoblast and osteoclast cells were performed and the comparative affinity of Tc(V)-DMS and Tc-BP was screened under diverse acidification conditions. Moreover, studies were also carried out on acid-base parameters related to the cellular uptake mechanism. Very specific pH-sensitive Tc(V)-DMS accumulation only in the osteoclastic system was detected, and use of Tc(V)-DMS in the differential detection of osteoblastic and osteoclastic metastases is discussed. (orig.)

  15. High-throughput analysis of protein-DNA binding affinity.

    Science.gov (United States)

    Franco-Zorrilla, José M; Solano, Roberto

    2014-01-01

    Sequence-specific protein-DNA interactions mediate most regulatory processes underlying gene expression, such as transcriptional regulation by transcription factors (TFs) or chromatin organization. Current knowledge about DNA-binding specificities of TFs is based mostly on low- to medium-throughput methodologies that are time-consuming and often fail to identify DNA motifs recognized by a TF with lower affinity but retaining biological relevance. The use of protein-binding microarrays (PBMs) offers a high-throughput alternative for the identification of protein-DNA specificities. PBM consists in an array of pseudorandomized DNA sequences that are optimized to include all the possible 10- or 11-mer DNA sequences, allowing the determination of binding specificities of most eukaryotic TFs. PBMs that can be synthesized by several manufacturing companies as single-stranded DNA are converted into double-stranded in a simple primer extension reaction. The protein of interest fused to an epitope tag is then incubated onto the PBM, and specific DNA-protein complexes are revealed in a series of immunological reactions coupled to a fluorophore. After scanning and quantifying PBMs, specific DNA motifs recognized by the protein are identified with ready-to-use scripts, generating comprehensive but accessible information about the DNA-binding specificity of the protein. This chapter describes detailed procedures for preparation of double-stranded PBMs, incubation with recombinant protein, and detection of protein-DNA complexes. Finally, we outline some cues for evaluating the biological role of DNA motifs obtained in vitro. PMID:24057393

  16. Surface-modified magnetic colloids for affinity adsorption of immunoglobulins

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Fernanda [School of Chemical Engineering, State University of Campinas, C.P. 6066, 13083-970 Campinas-SP (Brazil); Pinho, Samantha C. [School of Chemical Engineering, State University of Campinas, C.P. 6066, 13083-970 Campinas-SP (Brazil)], E-mail: samantha@usp.br; Zollner, Terezinha C.A. [School of Chemical Engineering, State University of Campinas, C.P. 6066, 13083-970 Campinas-SP (Brazil); Zollner, Ricardo L. [School of Medical Sciences, State University of Campinas, Campinas-SP (Brazil)], E-mail: zollner@unicamp.br; Cuyper, Marcel de [Interdisciplinary Research Centre, Katholieke Universiteit Leuven-Campus Kortrijk, B-8500 Kortrijk (Belgium)], E-mail: Marcel.DeCuyper@kulak.ac.be; Santana, Maria Helena A. [School of Chemical Engineering, State University of Campinas, C.P. 6066, 13083-970 Campinas-SP (Brazil)], E-mail: lena@feq.unicamp.br

    2008-07-15

    This work describes the preparation, characterization and in vitro adsorption tests of surface-modified magnetoliposomes for affinity binding of (i) anticardiolipin (isotype G) antibodies and (ii) specific isotype E antibodies generated by hypersensitivity reactions in humans with respiratory allergy. In the first case, cardiolipin embedded in the bilayer of magnetoliposomes was used as specific ligand. In the second case, antigenic proteins present in an extract of Dermatophagoids pteronyssinus and Blomia tropicalis mites were covalently coupled on the surface of magnetoliposomes via a diglycolic spacer arm, and used as specific ligands for IgE. Antibody adsorption was performed in a high-gradient magnetophoresis system, using either sera of healthy individuals or a pool of sera from autoimmune or allergic patients. The selectivity and capacity of the system were quantified by a frontal analysis in a capillary column, and by constructing breakthrough curves. The results show that the highest yield and selectivity were obtained if the ligand was extended into the aqueous layer surrounding the magnetoliposome surface. A 100% selectivity was obtained for adsorption of specific IgE, and 8% for IgG. These results demonstrate the potentialities of both types of surface-modified magnetic biocolloids in the field of in vitro diagnosis tests for allergic or autoimmune conditions.

  17. Surface-modified magnetic colloids for affinity adsorption of immunoglobulins

    International Nuclear Information System (INIS)

    This work describes the preparation, characterization and in vitro adsorption tests of surface-modified magnetoliposomes for affinity binding of (i) anticardiolipin (isotype G) antibodies and (ii) specific isotype E antibodies generated by hypersensitivity reactions in humans with respiratory allergy. In the first case, cardiolipin embedded in the bilayer of magnetoliposomes was used as specific ligand. In the second case, antigenic proteins present in an extract of Dermatophagoids pteronyssinus and Blomia tropicalis mites were covalently coupled on the surface of magnetoliposomes via a diglycolic spacer arm, and used as specific ligands for IgE. Antibody adsorption was performed in a high-gradient magnetophoresis system, using either sera of healthy individuals or a pool of sera from autoimmune or allergic patients. The selectivity and capacity of the system were quantified by a frontal analysis in a capillary column, and by constructing breakthrough curves. The results show that the highest yield and selectivity were obtained if the ligand was extended into the aqueous layer surrounding the magnetoliposome surface. A 100% selectivity was obtained for adsorption of specific IgE, and 8% for IgG. These results demonstrate the potentialities of both types of surface-modified magnetic biocolloids in the field of in vitro diagnosis tests for allergic or autoimmune conditions

  18. Surface-modified magnetic colloids for affinity adsorption of immunoglobulins

    Science.gov (United States)

    Martins, Fernanda; Pinho, Samantha C.; Zollner, Terezinha C. A.; Zollner, Ricardo L.; de Cuyper, Marcel; Santana, Maria Helena A.

    This work describes the preparation, characterization and in vitro adsorption tests of surface-modified magnetoliposomes for affinity binding of (i) anticardiolipin (isotype G) antibodies and (ii) specific isotype E antibodies generated by hypersensitivity reactions in humans with respiratory allergy. In the first case, cardiolipin embedded in the bilayer of magnetoliposomes was used as specific ligand. In the second case, antigenic proteins present in an extract of Dermatophagoids pteronyssinus and Blomia tropicalis mites were covalently coupled on the surface of magnetoliposomes via a diglycolic spacer arm, and used as specific ligands for IgE. Antibody adsorption was performed in a high-gradient magnetophoresis system, using either sera of healthy individuals or a pool of sera from autoimmune or allergic patients. The selectivity and capacity of the system were quantified by a frontal analysis in a capillary column, and by constructing breakthrough curves. The results show that the highest yield and selectivity were obtained if the ligand was extended into the aqueous layer surrounding the magnetoliposome surface. A 100% selectivity was obtained for adsorption of specific IgE, and 8% for IgG. These results demonstrate the potentialities of both types of surface-modified magnetic biocolloids in the field of in vitro diagnosis tests for allergic or autoimmune conditions.

  19. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Directory of Open Access Journals (Sweden)

    Rodríguez de Lores Arnaiz Georgina

    2006-04-01

    Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process

  20. Electron affinities of atoms, molecules, and radicals

    International Nuclear Information System (INIS)

    We review briefly but comprehensively the theoretical, semiempirical and experimental methods employed to determine electron affinities (EAs) of atoms, molecules and radicals, and summarize the EA data obtained by these methods. The detailed processes underlying the principles of the experimental methods are discussed very briefly. It is, nonetheless, instructive to recapitulate the definition of EA and those of the related quantities, namely, the vertical detachment energy, VDE, and the vertical attachment energy, VAE. The EA of an atom is defined as the difference in total energy between the ground state of the neutral atom (plus the electron at rest at infinity) and its negative ion. The EA of a molecule is defined as the difference in energy between the neutral molecule plus an electron at rest at infinity and the molecular negative ion when both, the neutral molecules and the negative ion, are in their ground electronic, vibrational and rotational states. The VDE is defined as the minimum energy required to eject the electron from the negative ion (in its ground electronic and nuclear state) without changing the internuclear separation; since the vertical transition may leave the neutral molecule in an excited vibrational/rotational state, the VDE, although the same as the EA for atoms is, in general, different (larger than), from the EA for molecules. Similarly, the VAE is defined as the difference in energy between the neutral molecule in its ground electronic, vibrational and rotational states plus an electron at rest at infinity and the molecular negative ion formed by addition of an electron to the neutral molecule without allowing a change in the intermolecular separation of the constituent nuclei; it is a quantity appropriate to those cases where the lowest negative ion state lies above the ground states of the neutral species and is less or equal to EA

  1. Mandibular dimensional changes and skeletal maturity

    Directory of Open Access Journals (Sweden)

    Priya Subramaniam

    2010-01-01

    Full Text Available Aim: Growth and development of the human face provides a fascinating interplay of form and function. Among the various facial bones, the mandible plays a very important role during various growth-modification therapies. These treatment modalities will yield a better result in less time if properly correlated with skeletal maturity. It is very essential to know where the site of growth occurs and also the time when it occurs or ceases to occur. This study was conducted to assess the mandibular dimensions at various stages of skeletal maturation. Materials and Methods: The subjects included 6 to 18-year-old children who were grouped according to their middle phalanx of the third finger stages of skeletal maturity. Lateral cephalographs were taken and, from their cephalometric tracings, linear and angular measurements of the mandible were made. The values obtained were subjected to statistical analysis. Results: Results showed that the mandibular height, length and symphysis thickness increased with skeletal maturity. An increase in angles SNB (Sella, Nasion, Supramentale and L1-MP (Long axis lower incisors- Mandibular plane and a decrease in the gonial angle and ANB (Subspinale, Nasion, Supramentale angle were observed. Conclusion: The study showed a significant correlation between mandibular growth and skeletal maturity.

  2. Fine-tuning of Substrate Affinity Leads to Alternative Roles of Mycobacterium tuberculosis Fe2+-ATPases.

    Science.gov (United States)

    Patel, Sarju J; Lewis, Brianne E; Long, Jarukit E; Nambi, Subhalaxmi; Sassetti, Christopher M; Stemmler, Timothy L; Argüello, José M

    2016-05-27

    Little is known about iron efflux transporters within bacterial systems. Recently, the participation of Bacillus subtilis PfeT, a P1B4-ATPase, in cytoplasmic Fe(2+) efflux has been proposed. We report here the distinct roles of mycobacterial P1B4-ATPases in the homeostasis of Co(2+) and Fe(2+) Mutation of Mycobacterium smegmatis ctpJ affects the homeostasis of both ions. Alternatively, an M. tuberculosis ctpJ mutant is more sensitive to Co(2+) than Fe(2+), whereas mutation of the homologous M. tuberculosis ctpD leads to Fe(2+) sensitivity but no alterations in Co(2+) homeostasis. In vitro, the three enzymes are activated by both Fe(2+) and Co(2+) and bind 1 eq of either ion at their transport site. However, equilibrium binding affinities and activity kinetics show that M. tuberculosis CtpD has higher affinity for Fe(2+) and twice the Fe(2+)-stimulated activity than the CtpJs. These parameters are paralleled by a lower activation and affinity for Co(2+) Analysis of Fe(2+) and Co(2+) binding to CtpD by x-ray absorption spectroscopy shows that both ions are five- to six-coordinate, constrained within oxygen/nitrogen environments with similar geometries. Mutagenesis studies suggest the involvement of invariant Ser, His, and Glu residues in metal coordination. Interestingly, replacement of the conserved Cys at the metal binding pocket leads to a large reduction in Fe(2+) but not Co(2+) binding affinity. We propose that CtpJ ATPases participate in the control of steady state Fe(2+) levels. CtpD, required for M. tuberculosis virulence, is a high affinity Fe(2+) transporter involved in the rapid response to iron dyshomeostasis generated upon redox stress. PMID:27022029

  3. New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-Affinity γ-Hydroxybutyrate (GHB) Binding Sites

    DEFF Research Database (Denmark)

    Vogensen, Stine B.; Marek, Ales; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin Holst Friborg; Clausen, Rasmus P.

    2013-01-01

    3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screen...

  4. Specific recognition of the C-terminal end of A beta 42 by a high affinity monoclonal antibody

    DEFF Research Database (Denmark)

    Axelsen, T.V.; Holm, A.; Birkelund, S.;

    2009-01-01

    The neurotoxic peptide A beta(42) is derived from the amyloid precursor protein by proteolytic cleavage and is deposited in the brain of patients suffering from Alzheimer's disease (AD). In this study we generate a high affinity monoclonal antibody that targets the C-terminal end of A beta(42) with...

  5. IT Governance Maturity: Developing a Maturity Model Using the Delphi Method

    NARCIS (Netherlands)

    Smits, Daniel; Hillegersberg, van Jos

    2015-01-01

    To advance in maturity, organizations should pay attention to both the hard and soft sides of IT governance (ITG). The hard side is related to processes and structure, the soft side to social aspects like behavior and organizational culture. This paper describes a study to develop an ITG maturity mo

  6. Maturity grids as tools for change management

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2011-01-01

    A maturity grid is a change management tool. Levels of maturity are assigned against aspects of an area under study, thus creating a grid. Text descriptions at the resulting intersections describe the typical behaviour exhibited by a firm for each area under study and from the basis for the...... assessment scale. It is a flexible assessment technique that is used by practitioners in industry, consultants and researchers in academia for diagnostic, reflective and improvement purposes. A large number of maturity grids have been proposed to assess a range of capabilities including quality management...... capabilities. Acknowledging that some compromise is necessary and appropriate in the interests of producing a useful and usable tool, this paper provides a set of four phases whilst the development process unfolds, namely: planning, development, evaluation and maintenance. A set of specific considerations to...

  7. Moving towards maturity in business model definitions

    DEFF Research Database (Denmark)

    Nielsen, Christian; Lund, Morten; Bukh, Per Nikolaj

    2014-01-01

    The field of business models has, as is the case with all emerging fields of practice, slowly matured through the development of frameworks, models, concepts and ideas over the last 15 years. New concepts, theories and models typically transcend a series of maturity phases. For the concept of...... Business Models, we are at the verge of moving from phase 2 to 3, after having spent a lot of time during the 1990’s and 2000’s arguing for the importance of understanding business models properly and discussing the content and potential building blocks of them. Therefore, in terms of maturity – the time...... for focusing on the more complex and dynamic aspects of business models seems to be right - right now!...

  8. Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity.

    Science.gov (United States)

    Gadhiya, Satishkumar; Madapa, Sudharshan; Kurtzman, Thomas; Alberts, Ian L; Ramsey, Steven; Pillarsetty, Nagavara-Kishore; Kalidindi, Teja; Harding, Wayne W

    2016-05-01

    Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (±)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (±)-stepholidine, were synthesized and evaluated for affinity at dopamine and σ receptors in order to evaluate effects on D3 and σ2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and σ2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for σ2 receptors as well as σ2 versus σ1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and σ receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds. PMID:27032890

  9. Genetic Algorithm-based Affine Parameter Estimation for Shape Recognition

    Directory of Open Access Journals (Sweden)

    Yuxing Mao

    2014-06-01

    Full Text Available Shape recognition is a classically difficult problem because of the affine transformation between two shapes. The current study proposes an affine parameter estimation method for shape recognition based on a genetic algorithm (GA. The contributions of this study are focused on the extraction of affine- invariant features, the individual encoding scheme, and the fitness function construction policy for a GA. First, the affine-invariant characteristics of the centroid distance ratios (CDRs of any two opposite contour points to the barycentre are analysed. Using different intervals along the azimuth angle, the different numbers of CDRs of two candidate shapes are computed as representations of the shapes, respectively. Then, the CDRs are selected based on predesigned affine parameters to construct the fitness function. After that, a GA is used to search for the affine parameters with optimal matching between candidate shapes, which serve as actual descriptions of the affine transformation between the shapes. Finally, the CDRs are resampled based on the estimated parameters to evaluate the similarity of the shapes for classification. The experimental results demonstrate the robust performance of the proposed method in shape recognition with translation, scaling, rotation and distortion.

  10. Einstein-Maxwell dynamics as a P(4) affine theory

    International Nuclear Information System (INIS)

    In Newtonian mechanics the energy of a particle is defined only up to an arbitrary additive constant. By using affine functions to model the Newtonian energy we show that it is possible to reformulate arbitrary time- and velocity-independent forces as R1 affine gauge potentials. Solutions of Newton's second law then define R1 affine energy geodesics, and the R1 flat gauge potentials are shown to correspond to conservative Newtonian forces. We generalize these ideas to relativistic mechanics by modeling the energy-momentum of classical particles as R4 affine four-vectors. If this R4 affine structure is to be compatible with the O(1,3) Riemannian structure of spacetime, then the R4 gauge potential must correspond to an antisymmetric tensor field on spacetime, and this field is identified with the electromagnetic field tensor. We are eventually led to a reformulation of the Einstein-Maxwell theory as a P(4) = O(1,3) x R4 affine gauge theory in which the timelike affine geodesics correspond to Lorentz-force-law trajectories, and the Einstein-Maxwell field equations are reformulated as gauge field equations in terms of the P(4) curvature

  11. Obesity accelerates secondary sexual maturity in girls

    Directory of Open Access Journals (Sweden)

    Meiriani Sari

    2012-07-01

    Full Text Available Background Worldwide incidence of obesity in children is increasing. Obesity may have many health effects including advancement of sexual maturity. Objective The aim of this study was to assess the timing of secondary sexual maturation in obese vs. non-obese girls. Methods Subjects were 105 obese and 105 non-obese girls, aged 7 to 8 years who had not entered puberty. Breast and pubic hair growth, secondary sexual characteristics, were assessed at baseline and every 4 months for two years. Onset of puberty was defined as Tanner stage for secondary sexual maturation of ≥ breast Tanner stage II (B2 and/or ≥ pubic hair Tanner stage II (P2. Survival analyses were used to estimate time to puberty in both groups. Cox regressions were used to analyze possible factors affecting secondary sexual maturation. Results Mean onset of breast budding (B2 was 7.8 (95% CI 7.7 to 7.8 years in obese girls vs. 8.6 (95% CI 8.5 to 8.6 years in non-obese girls (P<0.001. Mean onset of pubarche (P2 was 8.7 (95% CI 8.6 to 8.8 years in obese girls vs. 9.0 (95% CI 8.9 to 9.0 years in non-obese girls (P<0.001. Hazard ratios of obese girls to experience an earlier secondary sexual maturation at maturity level B2, B3 and P2 were 1.34 (95% CI 1.19 to 1.52, 6.91 (95% CI 3.90 to 12.24 and 3.78 (95% CI 2.42 to 5.89, respectively. Conclusions Obesity was associated with earlier onset of puberty in girls. Obese girls entered puberty approximately 3 to 9 months earlier than their non-obese peers.

  12. Capability Maturity Assessment Method of Civil Aircraft Customer Service System

    OpenAIRE

    Xu Jun; Chen Lin; Sun Lei

    2014-01-01

    According to the basic ideas of the maturity model (Capability Maturity Model, CMM), the maturity model and its capability maturity comprehensive evaluation method of civil aircrafts’ customer service system are established from five aspects: Engineering and technical support, marketing and customer support, spare parts support, flight training and technical publications. Referencing survey results of the customer service satisfaction from airlines, weights was ...

  13. How outsourcing affects ICT-Service Maturity

    OpenAIRE

    Bergholm, Tor

    2016-01-01

    The objective of this thesis is to explore how outsourcing affects IT Service Maturity. The thesis provides the answer by analysing the results of a series of IT Services Maturity Re-views performed at a large corporation during the first half year of 2014. The focus of the study is to show in detail the answers of what scenarios was taken into account while building the assessment survey. The author of the thesis works for Microsoft Finland as an IT Service Management and Program Managem...

  14. Compost maturity. Method book; Kompostin kypsyystestit. Menetelmaeohjeet

    Energy Technology Data Exchange (ETDEWEB)

    Itaevaara, M.; Vikman, M.; Kapanen, A. [VTT Technical Research Centre of Finland, Espoo (Finland); Venelampi, O.; Vuorinen, A. [Evira Finnish Food Safety Authority, Helsinki (Finland)

    2006-08-15

    The compost maturity method guidebook is intended for testing laboratories and composting plants that need to evaluate the maturity of compost samples, as well as for the self-management of composting plants. The guidebook provides detailed information, guidance and a theoretical background for performing the maturity tests. The tests are simple and easy to perform, but knowledge of composting processing is required when evaluating the tests results. Composting is a bioprocess which produces a good quality end product when properly managed. If improperly processed, however, the end product will be of poor quality and phytotoxic, therefore preventing its use for plant cultivation, and only be suitable for use in landfill constructions. Compost quality cannot be determined by using a single test; several tests have to be used in order to analyze the degradation phase of the compost, e.g. the stability level. In addition, the phytotoxicity of the compost also has to be analyzed. However, a distinction has to be drawn between phytotoxicity and persistant toxicity because the phytotoxic compounds, which are intermediates of the bioprocess, can be further degraded as composting proceeds. The guidebook describes how to combine test results in compost maturity assessment. In addition, troubleshooting hints are also given to avoid erroneous conclusions. The tests described in the guidebook are based on research performed at VTT over a period of several years. The book also includes information about basic compost analysis, as well as about several methods for estimating maturity, stability and toxicity. The limit values proposed in the book are not official limit values, but are based on research performed in projects by the VTT's research team. In reform of fertilizer product legislation by Ministry of Agriculture and Forestry, decree on compost products will set limit values for maturity and demand for determination of maturity. We have also included methods that are

  15. Posttesticular sperm maturation, infertility, and hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Marjorie Whitfield

    2015-01-01

    Full Text Available Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia affect male fertility but are most of the time studied from the angle of endocrine/testicular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, i.e., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.

  16. The Maturely, Immature Orientale Impact Basin

    Science.gov (United States)

    Cahill, J. T.; Lawrence, D. J.; Stickle, A. M.; Delen, O.; Patterson, G.; Greenhagen, B. T.

    2015-12-01

    Lunar surface maturity is consistently examined using the NIR optical maturity parameter (OMAT) [1]. However, the NIR only provides a perspective of the upper microns of the lunar surface. Recent studies of Lunar Prospector (LP) and Lunar Reconnaissance Orbiter data sets are now demonstrating additional measures of maturity with sensitivities to greater depths (~2 m) in the regolith. These include thermal infrared, S-band radar, and epithermal neutron data sets [2-4]. Interestingly, each of these parameters is directly comparable to OMAT despite each measuring slightly different aspects of the regolith. This is demonstrated by Lawrence et al. [3] where LP-measured non-polar highlands epithermal neutrons trend well with albedo, OMAT, and the Christensen Feature (CF). Lawrence et al. [3] used these data to derive and map highlands hydrogen (H) which is dominantly a function of H-implantation. With this in mind, areas of enriched-H are mature, while areas of depleted H are immature. Surface roughness as measured by S-band radar [4], also provides a measure of maturity. In this case, the circular polarization ratio (CPR) is high when rough and immature, and low when smooth and mature. Knowing this, one can recognize areas in the non-polar lunar highlands that show contradictory measures of maturity. For example, while many lunar localities show consistently immature albedo, OMAT, CF, CPR, and H concentrations (e.g., Tycho), others do not. Orientale basin is the most prominent example, shown to have immature CPR, CF, and H concentrations despite a relatively mature albedo and OMAT values as well as an old age determination (~3.8 Ga). To better understand how the lunar regolith is weathering in the upper 1-2 m of regolith with time we examine the Orientale basin relative to other highlands regions. [1] Lucey et al. (2000) JGR, 105, 20377; [2] Lucey et al. (2013) LPSC, 44, 2890; [3] Lawrence et al. (2015) Icarus, j.icarus.2015.01.005; [4] Neish et al. (2013) JGR, 118

  17. Obesity and secondary sexual maturity in boys

    OpenAIRE

    Modella Rahmani Femina; Madarina Julia; Soeroyo Machfudz

    2013-01-01

    Background Obesity induces earlier secondary sexual maturity in girls. However, results of studies in boys have been inconclusive. Objective To assess for an association between obesity and sexual maturity in boys. Methods This was a prospective cohort study on 133 obese and 133 matched-for-age, non-obese, prepubertal boys, aged 9 to 10 years. They were observed every 4 months for a two year period. Obesity was defined as the BMI ≥the 95th percentile, according to the Centers for Dise...

  18. Accelerated Maturation and Abnormal Morphology in the Preterm Neonatal Kidney

    Science.gov (United States)

    Sutherland, Megan R.; Gubhaju, Lina; Moore, Lynette; Kent, Alison L.; Dahlstrom, Jane E.; Horne, Rosemary S. C.; Hoy, Wendy E.; Bertram, John F.

    2011-01-01

    Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life. PMID:21636639

  19. Novel Kac-Moody-type affine extensions of non-crystallographic Coxeter groups

    CERN Document Server

    Dechant, Pierre-Philippe; Twarock, Reidun

    2011-01-01

    Motivated by recent results in mathematical virology, we present novel asymmetric Z[tau]-integer-valued affine extensions of the non-crystallographic Coxeter groups H_2, H_3 and H_4 derived in a Kac-Moody-type formalism. In particular, we show that the affine reflection planes which extend the Coxeter group H_3 generate (twist) translations along 2-, 3- and 5-fold axes of icosahedral symmetry and classify these translations in terms of Fibonacci recursion relations, thus providing a framework to explain results of Keef et al and Wardman at the group level. Finally, we extend this classification to the case of the non-crystallographic Coxeter groups H_2 and H_4. These results should have applications in physics (quasicrystals), biology (viruses) and chemistry (fullerenes).

  20. Affinity reagents for studying histone modifications & guidelines for their quality control.

    Science.gov (United States)

    Kungulovski, Goran; Mauser, Rebekka; Jeltsch, Albert

    2015-10-01

    Histone post-translational modifications (PTMs) have pivotal functions in many chromatin processes, which makes their detection and characterization an imperative in chromatin biology. The established approaches for histone PTM characterization are generally based on affinity reagents specific for modified histone tails such as antibodies and, most recently, recombinant reading domains. Hence, the proper performance of these reagents is a critical precondition for the validity of the generated experimental data. In this review, we evaluate and update the quality criteria for assessment of the binding specificity of histone PTM affinity reagents. In addition, we discuss in detail the advantages and pitfalls of using antibodies and recombinant reading domains in chromatin biology research. Reading domains provide key advantages, such as consistent quality and recombinant production, but the future will tell if this emerging technology keeps its promises. PMID:26541466

  1. Robotic high-throughput purification of affinity-tagged recombinant proteins.

    Science.gov (United States)

    Wiesler, Simone C; Weinzierl, Robert O J

    2015-01-01

    Affinity purification of recombinant proteins has become the method of choice to obtain good quantities and qualities of proteins for a variety of downstream biochemical applications. While manual or FPLC-assisted purification techniques are generally time-consuming and labor-intensive, the advent of high-throughput technologies and liquid handling robotics has simplified and accelerated this process significantly. Additionally, without the human factor as a potential source of error, automated purification protocols allow for the generation of large numbers of proteins simultaneously and under directly comparable conditions. The delivered material is ideal for activity comparisons of different variants of the same protein. Here, we present our strategy for the simultaneous purification of up to 24 affinity-tagged proteins for activity measurements in biochemical assays. The protocol described is suitable for the scale typically required in individual research laboratories. PMID:25749949

  2. Affine deformation tensor - a necessary object in GRT

    International Nuclear Information System (INIS)

    Einstein notions about the nature of gravitation are refined. The geometric gravitation theory (GGT) grounds are discussed. It is noted that there is no one of the important geometrical object in the Einstein gravitation theory (EGT) i.e. background affinity, which along with the metric tensor determines the gravitational gield energy density. Considering that it is not necessary to introduce background metrics, the author has introduced the background affinity and affine deformation tensor. The theory of black holes is considered as an alternative of EGT. 53 refs

  3. Synthesis and Image Matching On Structural Patterns Using Affine Transformation

    Directory of Open Access Journals (Sweden)

    S.Vandana

    2012-06-01

    Full Text Available This paper focuses in explaining a Fourier based affine estimator which is applied to the task of Image Synthesis. An affine transformation is an important class of linear 2-D geometric transformations which maps variables into new by applying a linear combination of translation, rotation, scaling and/or shearing operations. Conventional retrieval systems are very effective when knowledge information and query information are in a uniform orientation but fails in recognition when effects such as scaling, orientation exist. But as this technique is based on texture analysis, which is termed the affine estimator, it will even match the images with non-uniform orientation.

  4. Affinity- and topology-dependent bound on current fluctuations

    CERN Document Server

    Pietzonka, Patrick; Seifert, Udo

    2016-01-01

    We provide a proof of a recently conjectured universal bound on current fluctuations in Markovian processes. This bound establishes a link between the fluctuations of an individual observable current, the cycle affinities driving the system into a non-equilibrium steady state, and the topology of the network. The proof is based on a decomposition of the network into independent cycles with both positive affinity and positive stationary cycle current. This formalism allows for a refinement of the bound for systems in equilibrium or with locally vanishing affinities.

  5. Pepsin-modified chiral monolithic column for affinity capillary electrochromatography.

    Science.gov (United States)

    Hong, Tingting; Chi, Cuijie; Ji, Yibing

    2014-11-01

    Pepsin-modified affinity monolithic capillary electrochromatography, a novel microanalysis system, was developed by the covalent bonding of pepsin on silica monolith. The column was successfully applied in the chiral separation of (±)-nefopam. Furthermore, the electrochromatographic performance of the pepsin-functionalized monolith for enantiomeric analysis was evaluated in terms of protein content, pH of running buffer, sample volume, buffer concentration, applied voltage, and capillary temperature. The relative standard deviation (%RSD) values of retention time (intraday implied that the affinity monolith used in this research opens a new path of exploring particularly versatile class of enzymes to develop enzyme-modified affinity capillary monolith for enantioseparation. PMID:25146884

  6. ODE/IM correspondence and modified affine Toda field equations

    CERN Document Server

    Ito, Katsushi

    2014-01-01

    We study the two-dimensional affine Toda field equations for affine Lie algebra $\\hat{\\mathfrak{g}}$ modified by a conformal transformation and the associated linear equations. In the conformal limit, the associated linear problem reduces to a (pseudo-)differential equation. For classical affine Lie algebra $\\hat{\\mathfrak{g}}$, we obtain a (pseudo-)differential equation corresponding to the Bethe equations for the Langlands dual of the Lie algebra $\\mathfrak{g}$, which were found by Dorey et al. in study of the ODE/IM correspondence.

  7. Centro-affine hypersurface immersions with parallel cubic form

    OpenAIRE

    HILDEBRAND, Roland

    2012-01-01

    We consider non-degenerate centro-affine hypersurface immersions in R^n whose cubic form is parallel with respect to the Levi-Civita connection of the affine metric. There exists a bijective correspondence between homothetic families of proper affine hyperspheres with center in the origin and with parallel cubic form, and K\\"ochers conic omega-domains, which are the maximal connected sets consisting of invertible elements in a real semi-simple Jordan algebra. Every level surface of the omega ...

  8. Simultaneous purification and refolding of proteins by affinity precipitation and macro (affinity ligand)-facilitated three phase partitioning (MLFTPP).

    Science.gov (United States)

    Roy, Ipsita; Mondal, Kalyani; Gupta, Munishwar N

    2014-01-01

    This chapter describes two simple interrelated non-chromatographic methods of protein purification. In the first method, called affinity precipitation, inherent affinity of reversibly soluble-insoluble polymers (also called stimuli-sensitive or smart polymers) is exploited to form an affinity complex in free solution with target protein. The affinity complex is precipitated by a suitable change in the medium. The desired protein is dissociated from the smart polymer. In the second method called macro (affinity ligand)-facilitated three phase partitioning (MLFTPP), the affinity complex is precipitated at an interface between upper t-butanol-rich phase and lower aqueous phase. These three phases are achieved by adding appropriate amounts of ammonium sulfate and t-butanol to the initial crude extract. In the first protocol, sequential MLFTPP is used with two different smart polymers to purify pectinase and cellulase from a single crude preparation. The second protocol illustrates the application of the affinity precipitation in simultaneous purification and refolding of a urea-denatured xylanase. PMID:24648072

  9. Fluorescences Of Inclusion Oils With Respect To Their Maturities And Sources:Simulation In Diamond Anvil Cell

    Science.gov (United States)

    Chang, Y.; Huang, W.

    2007-12-01

    Evolution of fluorescence color of inclusion oils has been simulated by measuring in-situ the fluorescence of `live' oils generated from thirteen oil-prone kerogens from different depositional environments during a closed system pyrolysis in a diamond anvil cell at three heating rates (3, 8, and 25°C /min) up to 600°C. The measured fluorescence intensity of samples increases considerably within maturation intervals close to oil windows, while the fluorescence spectra of oils generated from all studied kerogens exhibit exclusively a progressive blue-shift of peak wavelengths (λmax) and red/green quotient (Q) upon increasing maturity. The observation is consistent with the maturity dependence of spectral shift trend widely recognized in natural hydrocarbon inclusions or crude oils. This study furthermore reveals that the acclaimed direction of spectral shift for inclusion oils is mostly independent of sources of their parental kerogens, implying that some reverse or anomalous trends reported in inclusion oils may be attributed to other processes subsequent to their generation, which significantly altered the fluorescence properties of oils. However, the experimental maturity corresponding to each color (λmax or Q) of oils can vary significantly (± 0.2 %Ro) among their sourced kerogens, suggesting that single fluorescence color of crude or inclusion oil is both maturity- and source-dependent and therefore may not be a good indication of its maturity. In addition, the blue-shift of cumulative oils generated from all kerogens approaches similar minima λmax around 564 nm or Q- value around 0.6 at maturity close to the middle or late stage of oil generation, implying that most late cumulative oils may exhibit similar colors. The oils generated in a maturity interval in late stage, however, can exhibit color of shorter wavelength less than the minimum.

  10. Uniform Orientation of Biotinylated Nanobody as an Affinity Binder for Detection of Bacillus thuringiensis (Bt) Cry1Ac Toxin

    OpenAIRE

    Min Li; Min Zhu; Cunzheng Zhang; Xianjin Liu; Yakun Wan

    2014-01-01

    Nanobodies are the smallest natural fragments with useful properties such as high affinity, distinct paratope and high stability, which make them an ideal tool for detecting target antigens. In this study, we generated and characterized nanobodies against the Cry1Ac toxin and applied them in a biotin-streptavidin based double antibodies (nanobodies) sandwich-ELISA (DAS-ELISA) assay. After immunizing a camel with soluble Cry1Ac toxin, a phage displayed library was constructed to generate Nbs a...

  11. Converging values: matures, boomers, xers, and nexters in the health care workforce.

    Science.gov (United States)

    Parsons, Lynn C

    2002-01-01

    The successful leader will try several strategies to bridge the generational gap and use the expertise of each cohort group to facilitate patient care. The energy, technoliteracy, and commitment to a balance between work and personal time by the Generation X and Nexters will complement the wisdom and nursing experience of the Mature and Baby Boomer generations. Time must be taken to understand the differences between the generations. Recognizing differences and appreciating the expertise that everyone brings to the workplace will create an environment that embraces generational diversity. Celebrating individual differences comes from taking time to learn about coworkers and will enhance a healthy work environment. PMID:12510502

  12. Using measurable physical characteristics to forecast beef heifer maturity: the identification of a maturity index.

    Science.gov (United States)

    Stockton, M C; Wilson, R K; Feuz, D M; Stalker, L A; Funston, R N

    2013-09-01

    A target BW is often used to estimate sexual maturity in beef heifers. The target BW, a percentage of mature BW, is generally an average for the breed, herd, or both. Heifer development is done in groups or herds, and not all heifers respond similarly to the same development regimen. Generally, heifers fed at a higher plane of nutrition gain more BW and tend to have increased pregnancy rates, but this usually increases feed costs. Therefore, determining when increased feed costs exceed the economic gains resulting from greater conception rates is critical and requires the inclusion of economic information and relationships. This research focused on the individual heifer as the decision point, and identification of the individual heifer target BW was based on clearly defined biological relationships observed before breeding. These relationships were captured in a maturity index (MI) identified through a series of steps and guided by current, accepted knowledge of heifer growth and development. Using an in-sample mean absolute percent error comparison, it was determined the MI was more accurate than the current group or herd methods in forecasting actual maturity and target BW. Maturity index demonstrated the flexibility in achieving similar maturities with beef heifers of varying characteristics using alternative nutritional programs. The MI was also the only significant predictor of first pregnancy. These results allow for more precision in determining sexual maturity and probability of first pregnancy in beef heifers and serve as the basis for future studies in determining profit differences among heifers. PMID:23825325

  13. A Maturity Model for Higher Education Institutions

    Directory of Open Access Journals (Sweden)

    Duarte Duarte

    2013-03-01

    Full Text Available The adoption of business process improvement strategies is currently a concern of most organizations. The quest for the benefits of this improvement on resource optimization and the responsiveness of the organizations has raised several proposals for process improvement methodologies. These approaches differ both in the principles that support them, and in the specific area to which they are intended. However, proposals and results of scientific research on process improvement in higher education institutions, extremely complex and unique organizations, are still scarce. This research project intends to propose the extension of a process improvement model for this particular type of organization. We propose to undertake a review of process areas, goals and practices used in reference maturity models, such as Capability Maturity Model Integration or Business Process Maturity Model, to determine which ones apply to academic organizations and which should be included, adapted or deleted. The resulting maturity model will be further validated in a Portuguese higher education institution. This study is being developed under the University of Algarve Informatics Engineering Doctorate program.

  14. Depressive Symptomatology among Very Early Maturing Girls.

    Science.gov (United States)

    Rierdan, Jill; Koff, Elissa

    1991-01-01

    The relationship between very early menarche and depression was studied in a sample of 488 girls (336 sixth graders and 152 seventh graders), less than 10 percent of whom were very early maturers. Very early menarche was associated with higher levels of depression than was more normative development. (SLD)

  15. Field Instruction and the Mature Student

    Science.gov (United States)

    Fox, Raymond

    2004-01-01

    As increasing numbers of mature students enter schools of social work, it is a challenge and an obligation for field instructors to discover ways to recruit and sustain them in the educational endeavor. Building upon three theoretical perspectives--Freire's pedagogy of the oppressed, Knowles's andragogy, and Schon's reflective learning and…

  16. Late Maturation of Auditory Perceptual Learning

    Science.gov (United States)

    Huyck, Julia Jones; Wright, Beverly A.

    2011-01-01

    Adults can improve their performance on many perceptual tasks with training, but when does the response to training become mature? To investigate this question, we trained 11-year-olds, 14-year-olds and adults on a basic auditory task (temporal-interval discrimination) using a multiple-session training regimen known to be effective for adults. The…

  17. Analyzing Project Management Maturity Level in Indonesia

    Directory of Open Access Journals (Sweden)

    Eliot Simangunsong

    2013-04-01

    Full Text Available Project management has been generally known and increasingly used by many organizations to gain competitive advantage. In this context, many studies have proposed maturity models to evaluate how project management knowledge has been deployed effectively and efficiently in or- ganization. As a developing country, Indonesia needs many development projects managed by government and private companies in different industries. Here, a study to assess project manage- ment maturity level in Indonesian businesses may bring insight about current business practices, which is important to speed up country development and business sustainability. Adapting the Project Management Maturity Model (ProMMM, a survey instrument has been developed and ap- plied to professionals from Jakarta and surrounding area. The result of analysis shows that con- struction and primary industry have a higher maturity level compare to manufacturing and servic- es. It is to be noted, however, that the level of project management understanding is low across in- dustries. This indicates that more quality project management training or certification is required to improve overall project management knowledge in Indonesia.

  18. Volatility Components, Affine Restrictions and Non-Normal Innovations

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Dorian, Christian;

    Recent work by Engle and Lee (1999) shows that allowing for long-run and short-run components greatly enhances a GARCH model's ability fit daily equity return dynamics. Using the risk-neutralization in Duan (1995), we assess the option valuation performance of the Engle-Lee model and compare it to...... GARCH models to four conditionally non-normal versions. As in Hsieh and Ritchken (2005), we find that non-affine models dominate affine models both in terms of fitting return and in terms of option valuation. For the affine models we find strong evidence in favor of the component structure for both...... returns and options, but for the non-affine models the evidence is much less strong in option valuation. The evidence in favor of the non-normal models is strong when fitting daily returns, but the non-normal models do not provide much improvement when valuing options....

  19. Rigid affine surfaces with isomorphic A2-cylinders

    OpenAIRE

    Dubouloz, Adrien

    2015-01-01

    We construct families of smooth affine surfaces with pairwise non isomorphic A 1-cylinders but whose A 2-cylinders are all isomorphic. These arise as complements of cuspidal hyperplane sections of smooth projective cubic surfaces.

  20. Kinetic modeling reveals a common death niche for newly formed and mature B cells.

    Directory of Open Access Journals (Sweden)

    Gitit Shahaf

    Full Text Available BACKGROUND: B lymphocytes are subject to elimination following strong BCR ligation in the absence of appropriate second signals, and this mechanism mediates substantial cell losses during late differentiation steps in the bone marrow and periphery. Mature B cells may also be eliminated through this mechanism as well as through normal turnover, but the population containing mature cells destined for elimination has not been identified. Herein, we asked whether the transitional 3 (T3 subset, which contains most newly formed cells undergoing anergic death, could also include mature B cells destined for elimination. METHODOLOGY/PRINCIPAL FINDINGS: To interrogate this hypothesis and its implications, we applied mathematical models to previously generated in vivo labeling data. Our analyses reveal that the death rate of T3 B cells is far higher than the death rates of all other splenic B cell subpopulations. Further, the model, in which the T3 pool includes both newly formed and mature primary B cells destined for apoptotic death, shows that this cell loss may account for nearly all mature B cell turnover. CONCLUSIONS/SIGNIFICANCE: This finding has implications for the mechanism of normal mature B cell turnover.

  1. Increased extracellular pressure provides a novel adjuvant stimulus for enhancement of conventional dendritic cell maturation strategies

    International Nuclear Information System (INIS)

    Dendritic cell (DC)-based vaccine strategies have gained increasing popularity in recent years. Methods for ex vivo generation of immunocompetent mature DCs still require optimization. DCs have been shown to phenotypically mature under elevated pressure. We compared the effects of pressure on DC maturation with LPS- and cytokine-stimulation. Human monocyte-derived immature or LPS- and cytokine-matured DCs were exposed to ambient or 40 mmHg increased pressure for 12 h, then assessed for expression of CD80, CD86, CD40, MHC-I/II, and inflammatory cytokine production. DCs were also evaluated for capacity to stimulate T-cell proliferation by co-culture with allogeneic lymphocytes. Pressure significantly increased cytokine production and expression of all surface molecules on immature DC other than MHC-I and CD40. Pressure/LPS-treated DCs displayed further upregulation of MHC-I, CD40, and IL-12p70. Cytokine-matured DCs appeared less responsive to pressure. T-cell proliferation correlated with MHC expression. Results suggest mechanical stimulation of DCs may provide a useful adjuvant to TLR-agonist maturation strategies.

  2. Histology of salmonid testes during maturation.

    Science.gov (United States)

    Dziewulska, Katarzyna; Domagała, Józef

    2003-03-01

    The commonly applied classification systems of fish gonad maturity divide the maturation process into certain stages. However, the scales do not entirely reflect the continuity of the maturation process. Based on light microscope observations, the paper describes a comprehensive pattern of testicular transformations during maturation. The study was carried out on precocious underyearling and 1-year-old males of sea trout (Salmo trutta m. trutta L.), 1-year-old males of salmon (Salmo salar L.), and males of brown trout (Salmo trutta m. fario L.) aged from 7 months to 4 years. A total of 821 gonads collected during all seasons of the year were examined. The fish were fixed in Bouin's fluid. Histological slides of the mid-part of the gonad were made using the standard paraffin technique. The 3-6 microm sections were stained with Heidenhain haematoxylin. Histological changes of testes during maturation were similar in the three species studied. Immature and resting gonads contained type A spermatogonia in lobules only. The appearance of cystic structures containing type B spermatogonia in the lobules signalled the beginning of the sexual cycle in male gonads. Type B spermatogonia underwent synchronous mitotic divisions resulting in an increase in the total number of spermatogonia. As the spermatogenesis continued, the gonads showed a gradual increase in the number of cysts containing cells at all the spermatogenetic stages: type B spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa. The well-formed spermatozoa were released to the lobule lumen once the Sertoli cells and spermatozoa connections broke up and the cyst disappeared. This was a continuous process observed throughout the spawning season. The spermatozoa were moved to the efferent duct. While some of the germ cells were completing spermatogenesis, the lobules contained less and less cysts with type B spermatogonia, primary and secondary spermatocytes, and spermatids; eventually all

  3. Power generation

    International Nuclear Information System (INIS)

    In the second half of twentieth century, nuclear power became an industrial reality. Now the operating 433 power plants, the 37 plants under construction, near 9000 years/reactor with only one serious accident with emission of radioactive material to the environment (Chernobyl) show the maturity of this technology. Today nuclear power contribute a 17% to the global generation and an increase of 75 % of the demand of electricity is estimated for 2020 while this demand is expected to triplicate by 2050. How this requirement can be satisfied? All the indicators seems to demonstrate that nuclear power will be the solution because of the shortage of other sources, the increase of the prices of the non renewable fuels and the scarce contribution of the renewable ones. In addition, the climatic changes produced by the greenhouse effect make even more attractive nuclear power. The situation of Argentina is analyzed and compared with other countries. The convenience of an increase of nuclear power contribution to the total national generation seems clear and the conclusion of the construction of the Atucha II nuclear power plant is recommended

  4. Note on Dilogarithm Identities from Nilpotent Double Affine Hecke Algebras

    Directory of Open Access Journals (Sweden)

    Tomoki Nakanishi

    2012-12-01

    Full Text Available Recently Cherednik and Feigin [arXiv:1209.1978] obtained several Rogers-Ramanujan type identities via the nilpotent double affine Hecke algebras (Nil-DAHA. These identities further led to a series of dilogarithm identities, some of which are known, while some are left conjectural. We confirm and explain all of them by showing the connection with Y-systems associated with (untwisted and twisted quantum affine Kac-Moody algebras.

  5. An affine sphere equation associated to Einstein toric surfaces

    OpenAIRE

    Mabuchi, Toshiki

    2007-01-01

    As seen in the works of Calabi, Cheng-Yau and Loftin, affine sphere equations have a close relationship with Kaehler-Einstein metrics. The main purpose of this note is to show that an equation analogous to those of hyperbolic affine spheres arises naturally from Kaehler-Einstein metrics on Einstein toric surfaces. The case for the remaining toric surfaces with Kaehler-Ricci solitons will also be discussed.

  6. The ABC's of affine Grassmannians and Hall-Littlewood polynomials

    OpenAIRE

    Dalal, Avinash J.; Morse, Jennifer

    2016-01-01

    We give a new description of the Pieri rule for k-Schur functions using the Bruhat order on the affine type-A Weyl group. In doing so, we prove a new combinatorial formula for representatives of the Schubert classes for the cohomology of affine Grassmannians. We show how new combinatorics involved in our formulas gives the Kostka-Foulkes polynomials and discuss how this can be applied to study the transition matrices between Hall-Littlewood and k-Schur functions.

  7. Peculiarities of Matter Motion in Metric-Affine Gravitational Theory

    OpenAIRE

    Babourova, O. V.; Frolov, B. N.; Koroliov, M. Yu.

    1995-01-01

    On the basis of the Lie derivative method in a metric-affine space-time it is shown that in the metric-affine gravitational theory the energy-momentum conservation law and therefore the equations of the matter motion are the consequence (as in the GR) of the gravitational field equations. The possi- bility of the detection of the space-time non-metric properties is discussed.

  8. Euclidean Reconstruction and Affine Camera Calibration Using Controlled Robot Motions

    OpenAIRE

    Horaud, Radu; Christy, Stéphane; Mohr, Roger

    1997-01-01

    We are addressing the problem of Euclidean reconstruction with an uncalibrated affine camera and the calibration of this camera. We investigate constraints under which the Euclidean shape and motion problem becomes linear. The theoretical study described in this paper leads us to impose some practical constraints that the camera is mounted onto a robot arm and that the robot is executing controlled motions whose parameters are known. The affine camera model considered here is just an approxim...

  9. Algebraic volume density property of affine algebraic manifolds

    OpenAIRE

    Kaliman, Shulim; Kutzschebauch, Frank

    2009-01-01

    We introduce the notion of algebraic volume density property for affine algebraic manifolds and prove some important basic facts about it, in particular that it implies the volume density property. The main results of the paper are producing two big classes of examples of Stein manifolds with volume density property. One class consists of certain affine modifications of $\\C^n$ equipped with a canonical volume form, the other is the class of all Linear Algebraic Groups equipped with the left i...

  10. Quantized gauge-affine gravity in the superfiber bundle approach

    OpenAIRE

    Meziane, A.; Tahiri, M

    2004-01-01

    The quantization of gauge-affine gravity within the superfiber bundle formalism is proposed. By introducing an even pseudotensorial 1-superform over a principal superfibre bundle with superconnection, we obtain the geometrical Becchi-Rouet-Stora-Tyutin (BRST) and anti-BRST transformations of the fields occurring in such a theory. Reducing the four-dimensional general affine group double-covering to the Poincare group double-covering we also find the BRST and anti-BRST transformations of the f...

  11. Affine invariant texture analysis based on structural properties

    OpenAIRE

    Zhang, Jianguo; Tan, Tieniu

    2002-01-01

    This paper presents a new texture analysis method based on structural properties. The texture features extracted using this algorithm are invariant to affine transform (including rotation, translation, scaling, and skewing). Affine invariant structural properties are derived based on texel areas. An area-ratio map utilizing these properties is introduced to characterize texture images. Histogram based on this map is constructed for texture classification. Efficiency of this algorithm for affi...

  12. Several Affinity Tags Commonly Used in Chromatographic Purification

    OpenAIRE

    Xinyu Zhao; Guoshun Li; Shufang Liang

    2013-01-01

    Affinity tags have become powerful tools from basic biological research to structural and functional proteomics. They were widely used to facilitate the purification and detection of proteins of interest, as well as the separation of protein complexes. Here, we mainly discuss the benefits and drawbacks of several affinity or epitope tags frequently used, including hexahistidine tag, FLAG tag, Strep II tag, streptavidin-binding peptide (SBP) tag, calmodulin-binding peptide (CBP), glutathione S...

  13. Skein Modules from Skew Howe Duality and Affine Extensions

    OpenAIRE

    Queffelec, Hoel

    2013-01-01

    We show that we can release the rigidity of the skew Howe duality process for ${\\mathfrak sl}_n$ knot invariants by rescaling the quantum Weyl group action, and recover skein modules for web-tangles. This skew Howe duality phenomenon can be extended to the affine ${\\mathfrak sl}_m$ case, corresponding to looking at tangles embedded in a solid torus. We investigate the relations between the invariants constructed by evaluation representations (and affinization of them) and usual skein modules,...

  14. Minimum information about a protein affinity reagent (MIAPAR).

    OpenAIRE

    Bourbeillon, Julie; Orchard, Sandra; Benhar, Itai; Borrebaeck, Carl; de Daruvar, Antoine; Dübel, Stefan; Frank, Ronald; Gibson, Frank; Gloriam, David; Haslam, Niall; Hiltker, Tara; Humphrey-Smith, Ian; Hust, Michael; Juncker, David; Koegl, Manfred

    2010-01-01

    We wish to alert your readers to MIAPAR, the minimum information about a protein affinity reagent. This is a proposal developed within the community as an important first step in formalizing standards in reporting the production and properties of protein binding reagents, such as antibodies, developed and sold for the identification and detection of specific proteins present in biological samples. It defines a checklist of required information, intended for use by producers of affinity reagen...

  15. A Drosophila Model to Image Phagosome Maturation

    Directory of Open Access Journals (Sweden)

    Douglas A. Brooks

    2013-03-01

    Full Text Available Phagocytosis involves the internalization of extracellular material by invagination of the plasma membrane to form intracellular vesicles called phagosomes, which have functions that include pathogen degradation. The degradative properties of phagosomes are thought to be conferred by sequential fusion with endosomes and lysosomes; however, this maturation process has not been studied in vivo. We employed Drosophila hemocytes, which are similar to mammalian professional macrophages, to establish a model of phagosome maturation. Adult Drosophila females, carrying transgenic Rab7-GFP endosome and Lamp1-GFP lysosome markers, were injected with E. coli DH5α and the hemocytes were collected at 15, 30, 45 and 60 minutes after infection. In wild-type females, E. coli were detected within enlarged Rab7-GFP positive phagosomes at 15 to 45 minutes after infection; and were also observed in enlarged Lamp1-GFP positive phagolysosomes at 45 minutes. Two-photon imaging of hemocytes in vivo confirmed this vesicle morphology, including enlargement of Rab7-GFP and Lamp1-GFP structures that often appeared to protrude from hemocytes. The interaction of endosomes and lysosomes with E. coli phagosomes observed in Drosophila hemocytes was consistent with that previously described for phagosome maturation in human ex vivo macrophages. We also tested our model as a tool for genetic analysis using 14-3-3e mutants, and demonstrated altered phagosome maturation with delayed E. coli internalization, trafficking and/or degradation. These findings demonstrate that Drosophila hemocytes provide an appropriate, genetically amenable, model for analyzing phagosome maturation ex vivo and in vivo.

  16. High affinity FRβ-specific CAR T cells eradicate AML and normal yeloid lineage without HSC toxicity

    Science.gov (United States)

    Lynn, Rachel C; Feng, Yang; Schutsky, Keith; Poussin, Mathilde; Kalota, Anna; Dimitrov, Dimiter S; Powell, Daniel J

    2016-01-01

    Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T-cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here, we isolated a high affinity (HA) folate receptor beta (FRβ)-specific scFv (2.48nM KD) for optimization of FRβ-redirected CAR T-cell therapy for AML. T-cells stably expressing the HA-FRβ CAR exhibited greatly enhanced antitumor activity against FRβ+ AML in vitro and in vivo compared to a low affinity (LA) FRβ CAR (54.3nM KD). Using the HA-FRβ IgG, FRβ expression was detectable in myeloid-lineage hematopoietic cells; however, expression in CD34+ hematopoietic stem cells (HSCs) was nearly undetectable. Accordingly, HA-FRβ CAR T-cells lysed mature CD14+ monocytes, while HSC colony formation was unaffected. Because of the potential for elimination of mature myeloid lineage, mRNA CAR electroporation for transient CAR expression was evaluated. mRNA-electroporated HA-FRβ CAR T-cells retained effective anti-tumor activity in vitro and in vivo. Together, our results highlight the importance of antibody affinity in target protein detection and CAR development and suggest that transient delivery of potent HA-FRβ CAR T-cells is highly effective against AML and reduces the risk for long-term myeloid toxicity. PMID:26898190

  17. Affinity Solvents for Intensified Organics Extraction: Development Challenges and Prospects

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In most organics extraction processes, the commonly used solvents employ solely physical interactions. Therefore, for the recovery and purification of products from complex mixtures, the selectivity and/or capacity of classical solvents towards the desired solutes is usually insufficient, enforcing the need for complex and thus expensive separation schemes. Significant simplification and cost-reduction can be achieved when affinity solvents would be available that are able to recognize the solutes of interest by their molecular structure. The main development challenges to establish such affinity solvents are: Selection and incorporation of molecular recognition and complexation capabilities; Evaluation of extraction capabilities; Efficient recovery and recycling of the affinity solvents; Implementation in industrial extraction equipment. This paper presents how these development challenges are addressed at the University of Twente, going all the way from affinity solvent design and synthesis, via high throughput screening and characterization up to pilot plant evaluation. Essential in the successful development of affinity solvents are structural cooperations with molecular chemists and custom synthesis companies for their design and synthesis. The various aspects are illustrated by several examples where newly developed environmentally benign affinity solvents appeared able to create major breakthroughs. The applications addressed involve oxygenates, sugars, and pharmaceutical ingredients, such as optical isomers and biomolecules.

  18. Biomarker distributions as maturity indicators in coals, coaly shales, and shales from Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Shen, J.C.; Huang, W.L. [Chinese Petroleum Corp, Miaoli (Taiwan)

    2007-10-15

    The distribution of hopanoids and alkanes in bitumen extracts of coals, coaly shales, and shales from northwestern Taiwan has been measured to assess the maturity of potential petroleum source rocks in the studied area. The C31 homohopane isomers of the studied coals and coaly shales attain equilibrium at maturity corresponding to 0.6% Ro measured in coals or 0.65% Ro in adjacent shales. A proposed parameter using hopanoid ratios reveals a more consistent trend and approaches a steady value at maturity similar to the C31 homohopane isomer ratio. The results show that the onset of the main phase of petroleum generation in northwestern Taiwan takes place at maturity corresponding to VR of 0.6% Ro measured in coals or coaly shales and probably higher VR in shales. The distribution of pristane, phytane n-C17 and n-C18 confirms the validity of the conventional maturity indicators if the samples are from the same source, but shows depositionalor organic-source controls. The source influence on the phytane/n-C18 ratio appears to be larger than that on the pristane/n-C17 ratio. The phytane/n-C18 ratio is also less sensitive to maturity than that of the pristane/n-C17 ratio. The pristane/phytane ratios in the studied coals and coaly shales, in contrast to the pristane/n-C-17 ratio, continue to decrease to maturities beyond the oil window up to 1.5% Ro and therefore may be applicable to high maturity sources.

  19. Characterization of monocyte-derived dendritic cells maturated with IFN-alpha

    DEFF Research Database (Denmark)

    Svane, I M; Nikolajsen, K; Walter, M R; Buus, S; Gad, M; Claesson, M H; Pedersen, Anders Elm

    2006-01-01

    Dendritic cells (DC) are promising candidates for cancer immunotherapy. These cells can be generated from peripheral blood monocytes cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). In order to obtain full functional capacity, maturation is required...

  20. Modeling petroleum generation and accumulation in Qarun field, north Western Desert, Egypt

    Energy Technology Data Exchange (ETDEWEB)

    Younes, Mohamed Abdel-Aziz [Alexandria Univ. (Egypt). Dept. Geology

    2011-09-15

    The Qarun area lies on the southeast flank of the Jurassic-Cretaceous Kattaniya uplift and the northwest flank of the Gindi Basin in the northernWestern Desert of Egypt, where many promising structural traps have been discovered within the inverted basin. The Rock-Eval pyrolysis technique carried out on 59 shale rock samples representing the stratigraphic succession of the well Qarun-5X revealed the presence of two excellent potential source rocks within the Khatatba and Abu Roash formations with different levels of thermal maturity. The burial history model proved that the shale rock of the Khatatba formation reached the late mature stage of oil generation at the vitrinite reflectance value of 1.35 Ro% between 100 to 80 Ma. Meanwhile, the shale rock of the Abu RoashGand F formation entered the earlymature stage of oil generation at the vitrinite reflectance value of 0.5-0.7 Ro% between 50 to 40 Ma. The geochemical fingerprints of 9 crude oil samples also support a genetic relation to multiple source rocks for oil generation. The crude oil produced from the Kharita formation has a low ratio of oleanane index <10% and high maturity level of C{sub 29}{alpha}{alpha}{alpha} Cholestane 20S/(20S+20R) ratio >0.5 and has the great affinity to be generated from shale section of the Khatatba formation that has amixed kerogen types II-III. Meanwhile, the biomarker fingerprints of crude oils produced from the Bahariya formation indicate a high oleanane index >20% and low ratios of C{sub 29}{alpha}{alpha}{alpha} Cholestane 20S/(20S+20R) <0.5. These characteristics referred their origin to the shale source rocks of the Abu Roash formation G and F which have mixed type II-III kerogen thatwere derived from amixed environment containing an admixture of continental and marginal marine organic matter and have the ability to generate mixed oil and gas accumulations under thermal maturation. The burial history modeling suggests that initial hydrocarbon expulsion from Jurassic source

  1. Oocyte-secreted factors in oocyte maturation media enhance subsequent development of bovine cloned embryos.

    Science.gov (United States)

    Su, Jianmin; Wang, Yongsheng; Zhang, Lei; Wang, Bo; Liu, Jun; Luo, Yan; Guo, Zekun; Quan, Fusheng; Zhang, Yong

    2014-04-01

    Successful in vitro maturation (IVM) and oocyte quality both affect the subsequent development of cloned embryos derived from somatic-cell nuclear transfer (SCNT). Developmental competence is usually lower in oocytes matured in vitro compared with those that matured in vivo, possibly due to insufficient levels of oocyte-secreted factors (OSFs) and disrupted oocyte-cumulus communication. This study investigated the effects of OSFs secreted by denuded oocytes (DOs) during IVM on the subsequent developmental competence of cloned bovine embryos. Cumulus-oocyte complexes (COCs) from antral follicles of slaughtered-cow ovaries collected from an abattoir were divided into four groups: COCs co-cultured with and without DOs in maturation media used for SCNT, as well as COCs co-cultured with and without DOs in maturation media used for in vitro fertilization (IVF). Based on the developmental competence and embryo quality of bovine embryos generated from these four groups, we found that co-culturing the COCs with DOs enhanced the in vitro development of IVF and cloned bovine embryos, and potentially generated more high-quality cloned blastocysts that possessed locus-specific histone modifications at levels similar to in vitro-fertilized embryos. These results strongly suggest that co-culturing COCs with DOs enhances subsequent developmental competence of cloned bovine embryo. PMID:24420374

  2. Maturation history modeling of Sufyan Depression, northwest Muglad Basin, Sudan

    Science.gov (United States)

    Wang, Ying; Liu, Luofu; An, Fuli; Wang, Hongmei; Pang, Xiongqi

    2016-08-01

    The Sufyan Depression is located in the northwest of Muglad Basin and is considered as a favorable exploration area by both previous studies and present oil shows. In this study, 16 wells are used or referred, the burial history model was built with new seismic, logging and well data, and the thermal maturity (Ro, %) of proved AG source rocks was predicted based on heat flow calculation and EASY %Ro modeling. The results show that the present heat flow range is 36 mW/m2∼50 mW/m2 (average 39 mW/m2) in 13 wells and 15 mW/m2∼55 mW/m2 in the whole depression. Accordingly, the geothermal gradient is 20 °C/km∼26 °C/km and 12 °C/km∼30 °C/km, respectively. The paleo-heat flow has three peaks, namely AG-3 period, lower Bentiu period and Early Paleogene, with the value decreases from the first to the last, which is corresponding to the tectonic evolution history. Corresponding to the heat flow distribution feature, the AG source rocks become mature earlier and have higher present marurity in the south area. For AG-2_down and AG-3_up source rocks that are proved to be good-excellent, most of them are mature with Ro as 0.5%-1.1%. But they can only generate plentiful oil and gas to charge reservoirs in the middle and south areas where their Ro is within 0.7%-1.1%, which is consistent with the present oil shows. Besides, the oil shows from AG-2_down reservoir in the middle area of the Sufyan Depression are believed to be contributed by the underlying AG-3_up source rock or the source rocks in the south area.

  3. Deformation equivalence of affine ruled surfaces

    OpenAIRE

    Flenner, Hubert; Kaliman, Shulim; ZAIDENBERG, MIKHAIL

    2013-01-01

    A smooth family $\\varphi:\\mathcal V\\to S$ of surfaces will be called {\\em completable} if there is a logarithmic deformation $(\\bar {\\mathcal V},{\\mathcal D})$ over $S$ so that ${\\mathcal V}=\\bar{\\mathcal V}\\backslash {\\mathcal D}$. Two smooth surfaces $V$ and $V'$ are said to be deformations of each other if there is a completable flat family ${\\mathcal V}\\to S$ of smooth surfaces over a connected base so that $V$ and $V'$ are fibers over suitable points $s,s'\\in S$. This relation generates ...

  4. Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

    OpenAIRE

    Kool, J.; N. Jonker; Irth, H.; Niessen, W.M.A.

    2011-01-01

    This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein–protein and protein–immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of prote...

  5. Leveraging People-Related Maturity Issues for Achieving Higher Maturity and Capability Levels

    Science.gov (United States)

    Buglione, Luigi

    During the past 20 years Maturity Models (MM) become a buzzword in the ICT world. Since the initial Crosby's idea in 1979, plenty of models have been created in the Software & Systems Engineering domains, addressing various perspectives. By analyzing the content of the Process Reference Models (PRM) in many of them, it can be noticed that people-related issues have little weight in the appraisals of the capabilities of organizations while in practice they are considered as significant contributors in traditional process and organizational performance appraisals, as stressed instead in well-known Performance Management models such as MBQA, EFQM and BSC. This paper proposes some ways for leveraging people-related maturity issues merging HR practices from several types of maturity models into the organizational Business Process Model (BPM) in order to achieve higher organizational maturity and capability levels.

  6. Transcriptional programs controlling perinatal lung maturation.

    Directory of Open Access Journals (Sweden)

    Yan Xu

    Full Text Available The timing of lung maturation is controlled precisely by complex genetic and cellular programs. Lung immaturity following preterm birth frequently results in Respiratory Distress Syndrome (RDS and Broncho-Pulmonary Dysplasia (BPD, which are leading causes of mortality and morbidity in preterm infants. Mechanisms synchronizing gestational length and lung maturation remain to be elucidated. In this study, we designed a genome-wide mRNA expression time-course study from E15.5 to Postnatal Day 0 (PN0 using lung RNAs from C57BL/6J (B6 and A/J mice that differ in gestational length by ∼30 hr (B6maturation. We identified both temporal and strain dependent gene expression patterns during lung maturation. For time dependent changes, cell adhesion, vasculature development, and lipid metabolism/transport were major bioprocesses induced during the saccular stage of lung development at E16.5-E17.5. CEBPA, PPARG, VEGFA, CAV1 and CDH1 were found to be key signaling and transcriptional regulators of these processes. Innate defense/immune responses were induced at later gestational ages (E18.5-20.5, STAT1, AP1, and EGFR being important regulators of these responses. Expression of RNAs associated with the cell cycle and chromatin assembly was repressed during prenatal lung maturation and was regulated by FOXM1, PLK1, chromobox, and high mobility group families of transcription factors. Strain dependent lung mRNA expression differences peaked at E18.5. At this time, mRNAs regulating surfactant and innate immunity were more abundantly expressed in lungs of B6 (short gestation than in A/J (long gestation mice, while expression of genes involved in chromatin assembly and histone modification were expressed at lower levels in B6 than in A/J mice. The present study systemically mapped key regulators

  7. Immobilized Metal Affinity Chromatography Coupled to Multiple Reaction Monitoring Enables Reproducible Quantification of Phospho-signaling.

    Science.gov (United States)

    Kennedy, Jacob J; Yan, Ping; Zhao, Lei; Ivey, Richard G; Voytovich, Uliana J; Moore, Heather D; Lin, Chenwei; Pogosova-Agadjanyan, Era L; Stirewalt, Derek L; Reding, Kerryn W; Whiteaker, Jeffrey R; Paulovich, Amanda G

    2016-02-01

    A major goal in cell signaling research is the quantification of phosphorylation pharmacodynamics following perturbations. Traditional methods of studying cellular phospho-signaling measure one analyte at a time with poor standardization, rendering them inadequate for interrogating network biology and contributing to the irreproducibility of preclinical research. In this study, we test the feasibility of circumventing these issues by coupling immobilized metal affinity chromatography (IMAC)-based enrichment of phosphopeptides with targeted, multiple reaction monitoring (MRM) mass spectrometry to achieve precise, specific, standardized, multiplex quantification of phospho-signaling responses. A multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay targeting phospho-analytes responsive to DNA damage was configured, analytically characterized, and deployed to generate phospho-pharmacodynamic curves from primary and immortalized human cells experiencing genotoxic stress. The multiplexed assays demonstrated linear ranges of ≥3 orders of magnitude, median lower limit of quantification of 0.64 fmol on column, median intra-assay variability of 9.3%, median inter-assay variability of 12.7%, and median total CV of 16.0%. The multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay enabled robust quantification of 107 DNA damage-responsive phosphosites from human cells following DNA damage. The assays have been made publicly available as a resource to the community. The approach is generally applicable, enabling wide interrogation of signaling networks. PMID:26621847

  8. Predicting the Impact of Missense Mutations on Protein-Protein Binding Affinity.

    Science.gov (United States)

    Li, Minghui; Petukh, Marharyta; Alexov, Emil; Panchenko, Anna R

    2014-04-01

    The crucial prerequisite for proper biological function is the protein's ability to establish highly selective interactions with macromolecular partners. A missense mutation that alters the protein binding affinity may cause significant perturbations or complete abolishment of the function, potentially leading to diseases. The availability of computational methods to evaluate the impact of mutations on protein-protein binding is critical for a wide range of biomedical applications. Here, we report an efficient computational approach for predicting the effect of single and multiple missense mutations on protein-protein binding affinity. It is based on a well-tested simulation protocol for structure minimization, modified MM-PBSA and statistical scoring energy functions with parameters optimized on experimental sets of several thousands of mutations. Our simulation protocol yields very good agreement between predicted and experimental values with Pearson correlation coefficients of 0.69 and 0.63 and root-mean-square errors of 1.20 and 1.90 kcal mol(-1) for single and multiple mutations, respectively. Compared with other available methods, our approach achieves high speed and prediction accuracy and can be applied to large datasets generated by modern genomics initiatives. In addition, we report a crucial role of water model and the polar solvation energy in estimating the changes in binding affinity. Our analysis also reveals that prediction accuracy and effect of mutations on binding strongly depends on the type of mutation and its location in a protein complex. PMID:24803870

  9. Development of an early maturing chickpea variety, BINASOLA-3

    International Nuclear Information System (INIS)

    Chickpea has higher yield potential, more important nutrients and diversified use than all other pulse crops in Bangladesh. Nevertheless, farmers are not very interested in growing this crop because the varieties have a long maturity period, small seed size and poor seed yielding. For this reason huge amounts of chickpea seeds are imported every year in exchange for valuable foreign currency. A mutation-breeding program was undertaken at Bangladesh Institute of Nuclear Agriculture (BINA) in 1989 to develop an early maturing, large seeded and high yielding variety of chickpea. Seeds of the two exotic lines G-97 (now Binasola-2) and G-319 were treated with gamma-rays, sodium azide and a combination of the two mutagens. The following doses of gamma rays: 0, 200, 300, 400 and 500 Gy, concentrations of sodium azide: 0.4 mM, and combined doses: 200 Gy+0.4 mM, 300 Gy+0.4 mM, 400 Gy+0.4 mM and 500 Gy+0.4 mM were used. In the first year, the treated seeds were grown dose-wise and raised as M1 generation during 1989. M2 seeds were harvested from 4,542 individual M1 plants. These were grown in plant- progeny- rows in M2 generation. Eighty-seven individual M2 plants were selected, from which 16 M4 lines were further selected and put into preliminary observation trials in M4. Among them, one elite mutant L-84, which was derived from a single plant in the population of the 200 Gy gamma-ray treated G-97 was tested in M5, M6 and M7 along with other mutants and its parent. Finally the mutant was evaluated in advanced, zonal yield trials and farmers field trials in the following generations from 1995-2001 along with two selected lines and three released varieties (Hyprosola, Binasola-2 and Barisola-3). All the selected lines were grown at different agro-ecological zones in Bangladesh to observe the yield and other potentiality. Mutant performance was evaluated under two management practices i.e., Research management and Farmers' management. In the research management practices, NPK

  10. Increased hemoglobin O2 affinity protects during acute hypoxia.

    Science.gov (United States)

    Yalcin, Ozlem; Cabrales, Pedro

    2012-08-01

    Acclimatization to hypoxia requires time to complete the adaptation mechanisms that influence oxygen (O(2)) transport and O(2) utilization. Although decreasing hemoglobin (Hb) O(2) affinity would favor the release of O(2) to the tissues, increasing Hb O(2) affinity would augment arterial O(2) saturation during hypoxia. This study was designed to test the hypothesis that pharmacologically increasing the Hb O(2) affinity will augment O(2) transport during severe hypoxia (10 and 5% inspired O(2)) compared with normal Hb O(2) affinity. RBC Hb O(2) affinity was increased by infusion of 20 mg/kg of 5-hydroxymethyl-2-furfural (5HMF). Control animals received only the vehicle. The effects of increasing Hb O(2) affinity were studied in the hamster window chamber model, in terms of systemic and microvascular hemodynamics and partial pressures of O(2) (Po(2)). Pimonidazole binding to hypoxic areas of mice heart and brain was also studied. 5HMF decreased the Po(2) at which the Hb is 50% saturated with O(2) by 12.6 mmHg. During 10 and 5% O(2) hypoxia, 5HMF increased arterial blood O(2) saturation by 35 and 48% from the vehicle group, respectively. During 5% O(2) hypoxia, blood pressure and heart rate were 58 and 30% higher for 5HMF compared with the vehicle. In addition, 5HMF preserved microvascular blood flow, whereas blood flow decreased to 40% of baseline in the vehicle group. Consequently, perivascular Po(2) was three times higher in the 5HMF group compared with the control group at 5% O(2) hypoxia. 5HMF also reduced heart and brain hypoxic areas in mice. Therefore, increased Hb O(2) affinity resulted in hemodynamics and oxygenation benefits during severe hypoxia. This acute acclimatization process may have implications in survival during severe environmental hypoxia when logistic constraints prevent chronic acclimatization. PMID:22636677

  11. Biomarker tests for fetal lung maturity.

    Science.gov (United States)

    Leung-Pineda, Van; Gronowski, Ann M

    2010-12-01

    The production of surfactant is a key step in fetal lung development. Surfactant decreases alveolar surface tension, thereby preventing alveolar collapse and allowing efficient gas exchange. The lack of adequate amounts of lung surfactant results in respiratory distress syndrome. Tests that assess surfactant concentrations in amniotic fluid are good predictors of infants that will not develop respiratory distress syndrome. The most frequently used test to assess fetal lung maturity (TDx FLM II) will not be available after December 2011. Therefore, we review the currently available tests for fetal lung maturity including lecithin:sphingomyelin ratio, phosphatidyl glycerol, surfactant:albumin ratio and lamellar body counts. Herein, we discuss their clinical utility and consider a suitable replacement for the future. PMID:21133706

  12. Modeling Non-maturing Savings Volumes

    OpenAIRE

    Paraschiv, Florentina

    2012-01-01

    In Basel II the regulators stress the importance of finding realistic volumes models for non-maturing accounts (NMAs), given their cash-flow uncer- tainty due to optionality. Focusing on Swiss savings accounts, we identify their seasonal pattern and we derive their sensitivity to market rates and to relevant macroeconomic factors. We derive a realistic volumes model, that allows for cash-flow forecasting, which is essential for liquidity management in banks.

  13. Elevated Social Anxiety among Early Maturing Girls

    OpenAIRE

    Blumenthal, Heidemarie; Leen-Feldner, Ellen W.; Babson, Kimberly A.; Gahr, Jessica L.; Trainor, Casey D.; Frala, Jamie L.

    2011-01-01

    Adolescence is a key period in terms of the development of anxiety psychopathology. An emerging literature suggests that early pubertal maturation is associated with enhanced vulnerability for anxiety symptomatology, although few studies have examined this association with regard to social anxiety. Accordingly, the current study was designed to further elucidate the relation between pubertal timing and social anxiety, with a focus on clarifying the role of gender. Participants were 138 adoles...

  14. Optimal time-consistent government debt maturity

    OpenAIRE

    Debortoli, Davide; Nunes, Ricardo; Yared, Pierre

    2016-01-01

    This paper develops a model of optimal government debt maturity in which the government cannot issue state-contingent bonds and cannot commit to fiscal policy. If the government can perfectly commit, it fully insulates the economy against government spending shocks by purchasing short-term assets and issuing long-term debt. These positions are quantitatively very large relative to GDP and do not need to be actively managed by the government. Our main result is that these conclu...

  15. Maturity of strategic management in organizations

    OpenAIRE

    Anna Witek-Crabb

    2015-01-01

    There is some ambivalence with regards to how to improve strategic management of organizations. On the one hand the example of big companies emphasizes the need for formalization and good organization of strategic management process. On the other hand the example of small companies draws attention to such qualities as entrepreneurship, flexibility and adaptability. The concept of strategic management maturity embraces both of these priorities. In this paper a framework for strategic managemen...

  16. Configuration Management Maturity in Scientific Facilities

    OpenAIRE

    Masoud Niknam; Pierre Bonnal; Jivka Ovtcharova

    2013-01-01

    Since the effectiveness of the development and operation of scientific facilities (especially those presenting specific hazards, such as ionizing radiations) relies heavily on state of the art practices, such as systems engineering and product lifecycle management, configuration management (CM) is becoming a key management process. However, while some maturity models exist to assess the degree of the implementation and effectiveness of many management processes, such as project management or ...

  17. DNA damage response during mouse oocyte maturation

    Czech Academy of Sciences Publication Activity Database

    Mayer, Alexandra; Baran, Vladimír; Sakakibara, Y.; Brzáková, Adéla; Ferencová, Ivana; Motlík, Jan; Kitajima, T.; Schultz, R. M.; Šolc, Petr

    2016-01-01

    Roč. 15, č. 4 (2016), s. 546-558. ISSN 1538-4101 R&D Projects: GA MŠk LH12057; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : double strand DNA breaks * DNA damage * MRE11 * meiotic maturation * mouse oocytes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.565, year: 2014

  18. Mediastinal Mature Teratoma Revealed by Empyema

    OpenAIRE

    Raoufi, Mohammed; Herrak, Laila; Benali, Anas; Achaachi, Leila; el Ftouh, Mustapha; Bellarbi, Salma; Tilfine, Charaf; Taouarsa, Firdaous

    2016-01-01

    Teratomas are germ cell tumors, manifested with a great variety of clinical features; the most common extragonadal site is the anterior mediastinum. In this case, we report the patient with a large mature mediastinal teratoma with several components of ectodermal and endothermal epithelium. A 24-year-old female patient presented with history of persistent chest pain and progressively aggravating dyspnea for the previous 3 months. A chest X-ray showed a large opacity of the entire left hemitho...

  19. Sardinia between Product Maturity and International Competition

    Directory of Open Access Journals (Sweden)

    Stefano Renoldi

    2014-06-01

    Full Text Available The paper proposes the analyses of medium-long term dynamics experienced by the accommodation system of Sardinia in the light of growing maturity signals for regional tourist product. Potentials referring to a progressive diversification of incoming markets have been assessed in the light of domestic and international outgoing flows, as well as of megatrends crossing international tourism market. Results underline an only apparent inconsistency with respect to the positive evolution of macroeconomic variables relating to regional hospitality sector.

  20. Okazaki fragment maturation: nucleases take centre stage

    Institute of Scientific and Technical Information of China (English)

    Li Zheng; Binghui Shen

    2011-01-01

    Completion of lagging strand DNA synthesis requires processing of up to 50 million Okazaki fragments per cell cycle in mammalian cells. Even in yeast, the Okazaki fragment maturation happens approximately a million times during a singte round of DNA replication. Therefore, efficient processing of Okazaki fragments is vital for DNA replication and cell proliferation. During this process,primase-synthesized RNA/DNA primers are removed, and Okazaki fragments are joined into an intact lagging strand DNA. The processing of RNA/DNA primers requires a group of structure-specific nucleases typified by flap endonuclease 1 (FEN1). Here, we summarize the distinct roles of these nucleases in different pathways for removal of RNA/DNA primers. Recent findings reveal that Okazaki fragment maturation is highly coordinated. The dynamic interactions of polymerase δ, FEN1 and DNA ligase I with proliferating cell nuclear antigen allow these enzymes to act sequentially during Okazaki fragment maturation. Such protein-protein interactions may be regulated by post-translational modifications. We also discuss studies using mutant mouse models that suggest two distinct cancer etiological mechanisms arising from defects in different steps of Okazaki fragment maturation.Mutations that affect the efficiency of RNA primer removal may result in accumulation of unligated nicks and DNA double-strand breaks. These DNA strand breaks can cause varying forms of chromosome aberrations, contributing to development of cancer that associates with aneuploidy and gross chromosomal rearrangement. On the other hand, mutations that impair editing out of polymerase o incorporation errors result in cancer displaying a strong mutator phenotype.

  1. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    International Nuclear Information System (INIS)

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting 3H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities

  2. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  3. The AGU Data Management Maturity Model Initiative

    Science.gov (United States)

    Bates, J. J.

    2015-12-01

    In September 2014, the AGU Board of Directors approved two initiatives to help the Earth and space sciences community address the growing challenges accompanying the increasing size and complexity of data. These initiatives are: 1) Data Science Credentialing: development of a continuing education and professional certification program to help scientists in their careers and to meet growing responsibilities and requirements around data science; and 2) Data Management Maturity (DMM) Model: development and implementation of a data management maturity model to assess process maturity against best practices, and to identify opportunities in organizational data management processes. Each of these has been organized within AGU as an Editorial Board and both Boards have held kick off meetings. The DMM model Editorial Board will recommend strategies for adapting and deploying a DMM model to the Earth and space sciences create guidance documents to assist in its implementation, and provide input on a pilot appraisal process. This presentation will provide an overview of progress to date in the DMM model Editorial Board and plans for work to be done over the upcoming year.

  4. Mitochondrial transcript maturation and its disorders.

    Science.gov (United States)

    Van Haute, Lindsey; Pearce, Sarah F; Powell, Christopher A; D'Souza, Aaron R; Nicholls, Thomas J; Minczuk, Michal

    2015-07-01

    Mitochondrial respiratory chain deficiencies exhibit a wide spectrum of clinical presentations owing to defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mitochondrial DNA (mtDNA) or mutations in nuclear genes coding for mitochondrially-targeted proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial biology including expression of mtDNA-encoded genes. Expression of the mitochondrial genes is extensively regulated at the post-transcriptional stage and entails nucleolytic cleavage of precursor RNAs, RNA nucleotide modifications, RNA polyadenylation, RNA quality and stability control. These processes ensure proper mitochondrial RNA (mtRNA) function, and are regulated by dedicated, nuclear-encoded enzymes. Recent growing evidence suggests that mutations in these nuclear genes, leading to incorrect maturation of RNAs, are a cause of human mitochondrial disease. Additionally, mutations in mtDNA-encoded genes may also affect RNA maturation and are frequently associated with human disease. We review the current knowledge on a subset of nuclear-encoded genes coding for proteins involved in mitochondrial RNA maturation, for which genetic variants impacting upon mitochondrial pathophysiology have been reported. Also, primary pathological mtDNA mutations with recognised effects upon RNA processing are described. PMID:26016801

  5. Towards mature design of PV powered products

    Energy Technology Data Exchange (ETDEWEB)

    Kan, S.Y.; Beers, S. van; Brezet, H. [Delft University of Technology, Faculty of Industrial Design Engineering, Section Design for Sustainability Program, Delft (Netherlands)

    2004-07-01

    The appearance and the actual convenience of photovoltaic (PV) powered products is often not properly considered in sustainable product design. We undertook an endeavour to identify and chart the main factors that need to be improved in order to reduce those neglects and to stimulate a broader use of PV cells in products. Moreover this paper will stir up the discussion on mature design quality of sustainable products. The word 'mature' can for instance mean timeless design. Some solutions and synergetic proper novel technologies are proposed for achieving a sound integration of PV cells into products. An introduction of mature design by optimizing ergonomical aspects, appearance and product - user context relevance is given. In particular the emphasis will be on good matching of the overall design with the PV cell characteristics. The uses of curved coloured PV surfaces will be highlighted. Although the appearance of PV powered products obviously contributes towards the diffusion of such products, it still remains a point of discussion what kind of appearance is decisive in this process. (orig.)

  6. Towards an energy management maturity model

    International Nuclear Information System (INIS)

    Energy management is becoming a priority as organizations strive to reduce energy costs, conform to regulatory requirements, and improve their corporate image. Despite the upsurge of interest in energy management standards, a gap persists between energy management literature and current implementation practices. This gap can be traced to the lack of an incremental improvement roadmap. In this paper we propose an Energy Management Maturity Model that can be used to guide organizations in their energy management implementation efforts to incrementally achieve compliance with energy management standards such as ISO 50001. The proposed maturity model is inspired on the Plan-Do-Check-Act cycle approach for continual improvement, and covers well-understood fundamental energy management activities common across energy management texts. The completeness of our proposal is then evaluated by establishing an ontology mapping against ISO 50001. - Highlights: • Real-world energy management activities are not aligned with the literature. • An Energy Management Maturity Model is proposed to overcome this alignment gap. • The completeness and relevance of proposed model are validated

  7. Uniform Orientation of Biotinylated Nanobody as an Affinity Binder for Detection of Bacillus thuringiensis (Bt) Cry1Ac Toxin

    Science.gov (United States)

    Li, Min; Zhu, Min; Zhang, Cunzheng; Liu, Xianjin; Wan, Yakun

    2014-01-01

    Nanobodies are the smallest natural fragments with useful properties such as high affinity, distinct paratope and high stability, which make them an ideal tool for detecting target antigens. In this study, we generated and characterized nanobodies against the Cry1Ac toxin and applied them in a biotin-streptavidin based double antibodies (nanobodies) sandwich-ELISA (DAS-ELISA) assay. After immunizing a camel with soluble Cry1Ac toxin, a phage displayed library was constructed to generate Nbs against the Cry1Ac toxin. Through successive rounds of affinity bio-panning, four nanobodies with greatest diversity in CDR3 sequences were obtained. After affinity determination and conjugating to HRP, two nanobodies with high affinity which can recognize different epitopes of the same antigen (Cry1Ac) were selected as capture antibody (Nb61) and detection antibody (Nb44). The capture antibody (Nb61) was biotinylated in vivo for directional immobilization on wells coated with streptavidin matrix. Both results of specificity analysis and thermal stability determination add support for reliability of the following DAS-ELISA with a minimum detection limit of 0.005 μg·mL−1 and a working range 0.010–1.0 μg·mL−1. The linear curve displayed an acceptable correlation coefficient of 0.9976. These results indicated promising applications of nanobodies for detection of Cry1Ac toxin with biotin-streptavidin based DAS-ELISA system. PMID:25474492

  8. Uniform Orientation of Biotinylated Nanobody as an Affinity Binder for Detection of Bacillus thuringiensis (Bt Cry1Ac Toxin

    Directory of Open Access Journals (Sweden)

    Min Li

    2014-12-01

    Full Text Available Nanobodies are the smallest natural fragments with useful properties such as high affinity, distinct paratope and high stability, which make them an ideal tool for detecting target antigens. In this study, we generated and characterized nanobodies against the Cry1Ac toxin and applied them in a biotin-streptavidin based double antibodies (nanobodies sandwich-ELISA (DAS-ELISA assay. After immunizing a camel with soluble Cry1Ac toxin, a phage displayed library was constructed to generate Nbs against the Cry1Ac toxin. Through successive rounds of affinity bio-panning, four nanobodies with greatest diversity in CDR3 sequences were obtained. After affinity determination and conjugating to HRP, two nanobodies with high affinity which can recognize different epitopes of the same antigen (Cry1Ac were selected as capture antibody (Nb61 and detection antibody (Nb44. The capture antibody (Nb61 was biotinylated in vivo for directional immobilization on wells coated with streptavidin matrix. Both results of specificity analysis and thermal stability determination add support for reliability of the following DAS-ELISA with a minimum detection limit of 0.005 μg·mL−1 and a working range 0.010–1.0 μg·mL−1. The linear curve displayed an acceptable correlation coefficient of 0.9976. These results indicated promising applications of nanobodies for detection of Cry1Ac toxin with biotin-streptavidin based DAS-ELISA system.

  9. Diamondoid hydrocarbons as a molecular proxy for thermal maturity and oil cracking: Geochemical models from hydrous pyrolysis

    Science.gov (United States)

    Wei, Z.; Moldowan, J.M.; Zhang, S.; Hill, R.; Jarvie, D.M.; Wang, Hongfang; Song, F.; Fago, F.

    2007-01-01

    A series of isothermal hydrous pyrolysis experiments was performed on immature sedimentary rocks and peats of different lithology and organic source input to explore the generation of diamondoids during the thermal maturation of sediments. Oil generation curves indicate that peak oil yields occur between 340 and 360 ??C, followed by intense oil cracking in different samples. The biomarker maturity parameters appear to be insensitive to thermal maturation as most of the isomerization ratios of molecular biomarkers in the pyrolysates have reached their equilibrium values. Diamondoids are absent from immature peat extracts, but exist in immature sedimentary rocks in various amounts. This implies that they are not products of biosynthesis and that they may be generated during diagenesis, not just catagenesis and cracking. Most importantly, the concentrations of diamondoids are observed to increase with thermal stress, suggesting that they can be used as a molecular proxy for thermal maturity of source rocks and crude oils. Their abundance is most sensitive to thermal exposure above temperatures of 360-370 ??C (R0 = 1.3-1.5%) for the studied samples, which corresponds to the onset of intense cracking of other less stable components. Below these temperatures, diamondoids increase gradually due to competing processes of generation and dilution. Calibrations were developed between their concentrations and measured vitrinite reflectance through hydrous pyrolysis maturation of different types of rocks and peats. The geochemical models obtained from these methods may provide an alterative approach for determining thermal maturity of source rocks and crude oils, particularly in mature to highly mature Paleozoic carbonates. In addition, the extent of oil cracking was quantified using the concentrations of diamondoids in hydrous pyrolysates of rocks and peats, verifying that these hydrocarbons are valuable indicators of oil cracking in nature. ?? 2006 Elsevier Ltd. All rights

  10. KAMG: A Tool for Converting Blood Ties and Affinity Ties into Adjacency Matrices

    Directory of Open Access Journals (Sweden)

    Hang Xiong

    2016-07-01

    Full Text Available Kinship Adjacency Matrix Generator (KAMG is a browser-based software for creating adjacency matrices using the information of kinship ties. Specifically, it is capable of converting the family trees in the format of GEDCOM files into adjacency matrices of blood relationship. With the data of intermarriages between different families, it can further create the adjacency matrix of affinity relationship for the families. The outcomes can be directly used to create networks. KAMG is written in JavaScript and implemented on web browsers. It is completely open source and the source code is publicly available on GitHub.

  11. Color-weak compensation using local affine isometry based on discrimination threshold matching

    OpenAIRE

    Mochizuki, Rika; Kojima, Takanori; Lenz, Reiner; Chao, Jinhui

    2015-01-01

    We develop algorithms for color-weak compensation and color-weak simulation based on Riemannian geometry models of color spaces. The objective function introduced measures the match of color discrimination thresholds of average normal observers and a color-weak observer. The developed matching process makes use of local affine maps between color spaces of color-normal and color-weak observers. The method can be used to generate displays of images that provide color-normal and color-weak obser...

  12. Isotope shift in the electron affinity of beryllium

    International Nuclear Information System (INIS)

    The study of the isotope shift in the electron affinity is interesting for probing correlation effects. Experiments that allow this property to be measured are rare, being difficult to realize, while accurate calculations remain a challenge for atomic theory. The present work focuses on the theoretical estimation of the isotope shift in the electron affinity of Be (2s2p 3Po), using correlated electronic wavefunctions obtained from multiconfiguration Hartree-Fock and configuration interaction variational calculations. The reliability of the correlation models is assessed from a comparison between the observed and theoretical electron affinities, and between theoretical isotope shift values for the 2s2p 3Po 2s21S transition of neutral beryllium. The sign and the magnitude of the difference between the mass polarization term expectation values obtained for the neutral atom and the negative ion are such that the resulting isotope shift in the electron affinity is 'anomalous', corresponding to a smaller electron affinity for the heavier isotope

  13. Coenzyme-like ligands for affinity isolation of cholesterol oxidase.

    Science.gov (United States)

    Xin, Yu; Lu, Liushen; Wang, Qing; Zhang, Ling; Tong, Yanjun; Wang, Wu

    2016-05-15

    Two coenzyme-like chemical ligands were designed and synthesized for affinity isolation of cholesterol oxidase (COD). To simulate the structure of natural coenzyme of COD (flavin adenine dinucleotide (FAD)), on Sepharose beads, 5-aminouracil, cyanuric chloride and 1, 4-butanediamine were composed and then modified. The COD gene from Brevibacterium sp. (DQ345780) was expressed in Escherichia coli BL21 (DE3), and then the sorbents were applied to adsorption analysis with the pure enzyme. Subsequently, the captured enzyme was applied to SDS-PAGE and activity analysis. As calculated, the theoretical maximum adsorption (Qmax) of the two affinity sorbents (RL-1 and RL-2) were ∼83.5 and 46.3mg/g wet gel; and the desorption constant Kd of the two sorbents were ∼6.02×10(-4) and 1.19×10(-4)μM. The proteins after cell lysis were applied to affinity isolation, and then after one step of affinity binding on the two sorbents, the protein recoveries of RL-1 and RL-2 were 9.2% and 9.7%; the bioactivity recoveries were 92.7% and 91.3%, respectively. SDS-PAGE analysis revealed that the purities of COD isolated with the two affinity sorbents were approximately 95%. PMID:26856529

  14. TÖLÖGÖN KASIMBEKOV’UN CETİLGEN KURAK (OLGUN NESİL ROMANINDA YAPI VE İZLEK: SOVYET TİPİ İNSAN YARATMA SÜRECİ/TÖLÖGÖN KASIMBEKOV THE CETİLGEN KURAK (MATURE GENERATION NOVEL STRUCTURE AND SUBJECT: SOVIET TYPE OF HUMAN CREATION PROCESS

    Directory of Open Access Journals (Sweden)

    Samet AZAP

    2016-06-01

    historical novels Kyrgyz writer Tölögön Kasımbekov clearly told the effects of the regime and its ideology on the social life in his book Mature Generation. The main characters of the novel Esen is a representation of Soviet-type people that the Soviets wanted to create. Esen is located in the center of the fiction and is given as a reflection of the ideal future of the Kyrgyz youth. The language of the type of people that the Soviets wanted to create will be Russian, his religion will be Christianity or atheism, and the culture will be the Russian culture. Esen grew up in orphans’ house and was fostered under the influence of Russian culture, became a teacher of Russian language and literature plays a key role in dramatic action in the novel as a carrier of this mission. Novel will be examined through the structural and thematic features. Structurally, time, place, and plot will be evaluated based on factors such as perspective and staff. As the thematic; the novel will be looked around subtitles of “communism and Russification” “self-actualization fight/individuality” “cultural alienation” and “love”.

  15. Morphology of preovulatory bovine follicles as related to oocyte maturation.

    Science.gov (United States)

    de Loos, F A; Bevers, M M; Dieleman, S J; Kruip, T A

    1991-03-01

    Thirty-three preovulatory bovine oocytes and their follicles were collected during the period of final maturation in normally cyclic cows. Cell density of the membrana granulosa, mitotic index of the membrana granulosa, and the occurrence of eosinophilic granulocytes around the basal membrane as well as the maturational stage of the oocyte were determined. Cell density decreased during the period of final maturation. Mitotic indices also decreased after an initial high level in the first hours of the final maturation. Eosinophilic granulocytes were only seen during the last hours of final maturation. The maturational stages of the oocytes were related to distinct maturational stages of the follicular wall as determined by morphological characteristics. We propose a scoring system for the maturity of the follicular wall based on cell density, presence of mitotic figures and the presence of eosinophilic granulocytes outside the vascular compartment. PMID:16726922

  16. Craniodental affinities of Southeast Asia's "negritos" and the concordance with their genetic affinities.

    Science.gov (United States)

    Bulbeck, David

    2013-01-01

    Genetic research into Southeast Asia's "negritos" has revealed their deep-rooted ancestry, with time depth comparable to that of Southwest Pacific populations. This finding is often interpreted as evidence that negritos, in contrast to other Southeast Asians, can trace much of their ancestry directly back to the early dispersal of Homo sapiens in the order of 70 kya from Africa to Pleistocene New Guinea and Australia. One view on negritos is to lump them and Southwest Pacific peoples into an "Australoid" race whose geographic distribution had included Southeast Asia prior to the Neolithic incursion of "Mongoloid" farmers. Studies into Semang osteology have revealed some hints of Southwest Pacific affinities in cranial shape, dental morphology, and dental metrical "shape." On the other hand, the Andamanese have been shown to resemble Africans in their craniometrics and South Asians in their dental morphology, while Philippine negritos resemble Mongoloid Southeast Asians in these respects and also in their dental metrics. This study expands the scope of negrito cranial comparisons by including Melayu Malays and additional coverage of South Asians. It highlights the distinction between the Mongoloid-like Philippine negritos and the Andamanese and Semang (and Senoi of Malaya) with their non-Mongoloid associations. It proposes that the early/mid-Holocene dispersal of the B4a1a mitochondrial DNA clade across Borneo, the Philippines, and Taiwan may be important for understanding the distinction between Philippine and other negritos. PMID:24297222

  17. A method for counting cotton mature fibers per seed

    OpenAIRE

    sprotocols

    2015-01-01

    Cotton is the most important textile fiber crop in the world. With expect to improve cotton fiber yield, many studies have tried to increase fiber number per seed. Estimating mature fiber number exactly is becoming more necessary, because only about thirty percentages of differentiated fiber cells could develop to mature fibers. To date, there is no method for counting mature fibers, except some ones for early fiber cells. Here, we describe a fast and easy approach for counting mature fibers ...

  18. Proteomic analysis and candidate allergenic proteins in Populus deltoides CL. "2KEN8" mature pollen.

    Science.gov (United States)

    Zhang, Jin; Wu, Li-Shuan; Fan, Wei; Zhang, Xiao-Ling; Jia, Hui-Xia; Li, Yu; Yin, Ya-Fang; Hu, Jian-Jun; Lu, Meng-Zhu

    2015-01-01

    Proteomic analysis was used to generate a map of Populus deltoides CL. "2KEN8" mature pollen proteins. By applying 2-D electrophoresis, we resolved 403 protein spots from mature pollen. Using the matrix-assisted laser desorption/ionization time time-of-flight/time-of-flight tandem mass spectrometry method, we identified 178 distinct proteins from 218 protein spots expressed in mature pollen. Moreover, out of these, 28 proteins were identified as putative allergens. The expression patterns of these putative allergen genes indicate that several of these genes are highly expressed in pollen. In addition, the members of profilin allergen family were analyzed and their expression patterns were compared with their homologous genes in Arabidopsis and rice. Knowledge of these identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with poplar pollen allergy. PMID:26284084

  19. k-Schur functions and affine Schubert calculus

    CERN Document Server

    Lam, Thomas; Morse, Jennifer; Schilling, Anne; Shimozono, Mark; Zabrocki, Mike

    2014-01-01

    This book gives an introduction to the very active field of combinatorics of affine Schubert calculus, explains the current state of the art, and states the current open problems. Affine Schubert calculus lies at the crossroads of combinatorics, geometry, and representation theory. Its modern development is motivated by two seemingly unrelated directions. One is the introduction of k-Schur functions in the study of Macdonald polynomial positivity, a mostly combinatorial branch of symmetric function theory. The other direction is the study of the Schubert bases of the (co)homology of the affine Grassmannian, an algebro-topological formulation of a problem in enumerative geometry. This is the first introductory text on this subject. It contains many examples in Sage, a free open source general purpose mathematical software system, to entice the reader to investigate the open problems. This book is written for advanced undergraduate and graduate students, as well as researchers, who want to become familiar with ...

  20. Enhancing Community Detection By Affinity-based Edge Weighting Scheme

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Andy [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sanders, Geoffrey [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Henson, Van [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vassilevski, Panayot [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-10-05

    Community detection refers to an important graph analytics problem of finding a set of densely-connected subgraphs in a graph and has gained a great deal of interest recently. The performance of current community detection algorithms is limited by an inherent constraint of unweighted graphs that offer very little information on their internal community structures. In this paper, we propose a new scheme to address this issue that weights the edges in a given graph based on recently proposed vertex affinity. The vertex affinity quantifies the proximity between two vertices in terms of their clustering strength, and therefore, it is ideal for graph analytics applications such as community detection. We also demonstrate that the affinity-based edge weighting scheme can improve the performance of community detection algorithms significantly.

  1. Semisupervised Clustering for Networks Based on Fast Affinity Propagation

    Directory of Open Access Journals (Sweden)

    Mu Zhu

    2013-01-01

    Full Text Available Most of the existing clustering algorithms for networks are unsupervised, which cannot help improve the clustering quality by utilizing a small number of prior knowledge. We propose a semisupervised clustering algorithm for networks based on fast affinity propagation (SCAN-FAP, which is essentially a kind of similarity metric learning method. Firstly, we define a new constraint similarity measure integrating the structural information and the pairwise constraints, which reflects the effective similarities between nodes in networks. Then, taking the constraint similarities as input, we propose a fast affinity propagation algorithm which keeps the advantages of the original affinity propagation algorithm while increasing the time efficiency by passing only the messages between certain nodes. Finally, by extensive experimental studies, we demonstrate that the proposed algorithm can take fully advantage of the prior knowledge and improve the clustering quality significantly. Furthermore, our algorithm has a superior performance to some of the state-of-art approaches.

  2. Single-cell measurement of red blood cell oxygen affinity

    CERN Document Server

    Caprio, Di; Higgins, John M; Schonbrun, Ethan

    2015-01-01

    Oxygen is transported throughout the body by hemoglobin in red blood cells. While the oxygen affinity of blood is well understood and is routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of red blood cell volume and hemoglobin concentration are taken millions of times per day by clinical hematology analyzers and are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume and hemoglobin concentration for individual red blood cells in high-throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.5%, which corresponds to the maximum slope of the oxygen-hemoglobin dissociation curve. In addition, single-cell oxygen affinity is positively correlated with hemoglobin concentr...

  3. Properties of the Affine Invariant Ensemble Sampler in high dimensions

    CERN Document Server

    Huijser, David; Brewer, Brendon J

    2015-01-01

    We present theoretical and practical properties of the affine-invariant ensemble sampler Markov chain Monte Carlo method. In high dimensions the affine-invariant ensemble sampler shows unusual and undesirable properties. We demonstrate this with an $n$-dimensional correlated Gaussian toy problem with a known mean and covariance structure, and analyse the burn-in period. The burn-in period seems to be short, however upon closer inspection we discover the mean and the variance of the target distribution do not match the expected, known values. This problem becomes greater as $n$ increases. We therefore conclude that the affine-invariant ensemble sampler should be used with caution in high dimensional problems. We also present some theoretical results explaining this behaviour.

  4. Evaluation Codes from an Affine Veriety Code Perspective

    DEFF Research Database (Denmark)

    Geil, Hans Olav

    2008-01-01

    Evaluation codes (also called order domain codes) are traditionally introduced as generalized one-point geometric Goppa codes. In the present paper we will give a new point of view on evaluation codes by introducing them instead as particular nice examples of affine variety codes. Our study...... includes a reformulation of the usual methods to estimate the minimum distances of evaluation codes into the setting of affine variety codes. Finally we describe the connection to the theory of one-pointgeometric Goppa codes. Contents 4.1 Introduction...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 4.2 Affine variety codes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 4.3 Some Gr¨obner basis theoretical tools . . . . . . . . . . . . . . . . . . . . . . . 155 4.4 A bound on the minimum distance of C(I,L) . . . . . . . . . . . . . . . . . . 157 4.5 The Feng-Rao bound for...

  5. EphA7 signaling guides cortical dendritic development and spine maturation

    Science.gov (United States)

    Clifford, Meredith A.; Athar, Wardah; Leonard, Carrie E.; Russo, Alexandra; Sampognaro, Paul J.; Van der Goes, Marie-Sophie; Burton, Denver A.; Zhao, Xiumei; Lalchandani, Rupa R.; Sahin, Mustafa; Vicini, Stefano; Donoghue, Maria J.

    2014-01-01

    The process by which excitatory neurons are generated and mature during the development of the cerebral cortex occurs in a stereotyped manner; coordinated neuronal birth, migration, and differentiation during embryonic and early postnatal life are prerequisites for selective synaptic connections that mediate meaningful neurotransmission in maturity. Normal cortical function depends upon the proper elaboration of neurons, including the initial extension of cellular processes that lead to the formation of axons and dendrites and the subsequent maturation of synapses. Here, we examine the role of cell-based signaling via the receptor tyrosine kinase EphA7 in guiding the extension and maturation of cortical dendrites. EphA7, localized to dendritic shafts and spines of pyramidal cells, is uniquely expressed during cortical neuronal development. On patterned substrates, EphA7 signaling restricts dendritic extent, with Src and Tsc1 serving as downstream mediators. Perturbation of EphA7 signaling in vitro and in vivo alters dendritic elaboration: Dendrites are longer and more complex when EphA7 is absent and are shorter and simpler when EphA7 is ectopically expressed. Later in neuronal maturation, EphA7 influences protrusions from dendritic shafts and the assembling of synaptic components. Indeed, synaptic function relies on EphA7; the electrophysiological maturation of pyramidal neurons is delayed in cultures lacking EphA7, indicating that EphA7 enhances synaptic function. These results provide evidence of roles for Eph signaling, first in limiting the elaboration of cortical neuronal dendrites and then in coordinating the maturation and function of synapses. PMID:24707048

  6. Maturation and electrophysiological properties of human pluripotent stem cell‐derived oligodendrocytes

    Science.gov (United States)

    Livesey, Matthew R.; Magnani, Dario; Cleary, Elaine M.; Vasistha, Navneet A.; James, Owain T.; Selvaraj, Bhuvaneish T.; Burr, Karen; Shaw, Christopher E.; Kind, Peter C.; Hardingham, Giles E.; Wyllie, David J.A.

    2016-01-01

    Abstract Rodent‐based studies have shown that the membrane properties of oligodendrocytes play prominent roles in their physiology and shift markedly during their maturation from the oligodendrocyte precursor cell (OPC) stage. However, the conservation of these properties and maturation processes in human oligodendrocytes remains unknown, despite their dysfunction being implicated in human neurodegenerative diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Here, we have defined the membrane properties of human oligodendrocytes derived from pluripotent stem cells as they mature from the OPC stage, and have identified strong conservation of maturation‐specific physiological characteristics reported in rodent systems. We find that as human oligodendrocytes develop and express maturation markers, they exhibit a progressive decrease in voltage‐gated sodium and potassium channels and a loss of tetrodotoxin‐sensitive spiking activity. Concomitant with this is an increase in inwardly rectifying potassium channel activity, as well as a characteristic switch in AMPA receptor composition. All these steps mirror the developmental trajectory observed in rodent systems. Oligodendrocytes derived from mutant C9ORF72‐carryng ALS patient induced pluripotent stem cells did not exhibit impairment to maturation and maintain viability with respect to control lines despite the presence of RNA foci, suggesting that maturation defects may not be a primary feature of this mutation. Thus, we have established that the development of human oligodendroglia membrane properties closely resemble those found in rodent cells and have generated a platform to enable the impact of human neurodegenerative disease‐causing mutations on oligodendrocyte maturation to be studied. Stem Cells 2016;34:1040–1053 PMID:26763608

  7. 7 CFR 1427.174 - Maturity of seed cotton loans.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Maturity of seed cotton loans. 1427.174 Section 1427..., DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.174 Maturity of seed cotton loans. Seed cotton loans mature on demand by CCC but no later than May 31...

  8. MD3M: The Master Data Management Maturity Model

    NARCIS (Netherlands)

    Spruit, Marco; Pietzka, Katharina

    2015-01-01

    This research aims to assess the master data maturity of an organization. It is based on thorough literature study to derive the main concepts and best practices in master data maturity assessment. A maturity matrix relating 13 focus areas and 65 capabilities was designed and validated. Furthermore,

  9. On maturation in the eggs of Limnaea stagnalis L

    NARCIS (Netherlands)

    Raven, Chr.P.

    1949-01-01

    1. The maturation divisions of the egg of Limnaea stagnalis L. have been studied. 2. The haploid number of chromosomes is 18. 3. At the telophase of the first maturation division, the central group of dyads reaches the surface of the inner central body of the first maturation amphiaster. 4. This cen

  10. Rapidly growing mature teratoma in the anterior mediastinum: case report

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Kyung Hwa; Jung, Gyoo Sik; Kim, Sang Heum; Huh, Jin Do; Cho, Young Duk; Chun, Bong Kwon [Kosin University College of Medicine, Busan (Korea, Republic of)

    2002-11-01

    Mature teratoma is a benign tumor composed of a number of different types of well-differentiated tissues. Mature teratomas of the mediastinum usually grow slowly and are commonly asymptomatic. We report a case of mediastinal mature teratoma with rapid growth resulting in rupture.

  11. A Bootstrap Approach of Benchmarking Organizational Maturity Model of Software Product With Educational Maturity Model

    Directory of Open Access Journals (Sweden)

    R.Manjula

    2012-06-01

    Full Text Available This Software product line engineering is an inter-disciplinary concept. It spans the dimensions of business, architecture, process, and the organization. Similarly, Education System engineering is also an inter-disciplinary concept, which spans the dimensions of academic, infrastructure, facilities, administration etc. Some of the potential benefits of this approach include continuous improvements in System quality and adhering to global standards. The increasing competency in IT and Educational Sectors necessitates a process maturity evaluation methodology. Accordingly, this paper presents an organizational maturity model for Education system for evaluating the maturity of multi- dimension factors and attributes of an Education System. Assessment questionnaires and a rating methodology comprise the framework of this Educational maturity model. The objective and design of the questionnaires are to collect information about the Education system engineering process from the multi perspectives of academic, infrastructure, administration, facilities etc. Furthermore, we conducted one case study and reported the assessment results using the organizational maturity model presented in this paper.

  12. Ferromagnetic Levan Composite: An Affinity Matrix to Purify Lectin

    Directory of Open Access Journals (Sweden)

    Renata Angeli

    2009-01-01

    Full Text Available A simple and inexpensive procedure used magnetite and levan to synthesize a composite recovered by a magnetic field. Lectins from Canavalia ensiformis (Con A and Cratylia mollis (Cramoll 1 and Cramoll 1,4 did bind specifically to composite. The magnetic property of derivative favored washing out contaminating proteins and recovery of pure lectins with glucose elution. Cramoll 1 was purified by this affinity binding procedure in two steps instead of a previous three-step protocol with ammonium sulfate fractionation, affinity chromatography on Sephadex G-75, and ion exchange chromatography through a CM-cellulose column.

  13. Ferromagnetic levan composite: an affinity matrix to purify lectin.

    Science.gov (United States)

    Angeli, Renata; da Paz, Nathalia V N; Maciel, Jackeline C; Araújo, Flávia F B; Paiva, Patrícia M G; Calazans, Glícia M T; Valente, Ana Paula; Almeida, Fábio C L; Coelho, Luana C B B; Carvalho, Luiz B; Silva, Maria da Paz C; dos Santos Correia, Maria Tereza

    2009-01-01

    A simple and inexpensive procedure used magnetite and levan to synthesize a composite recovered by a magnetic field. Lectins from Canavalia ensiformis (Con A) and Cratylia mollis (Cramoll 1 and Cramoll 1, 4) did bind specifically to composite. The magnetic property of derivative favored washing out contaminating proteins and recovery of pure lectins with glucose elution. Cramoll 1 was purified by this affinity binding procedure in two steps instead of a previous three-step protocol with ammonium sulfate fractionation, affinity chromatography on Sephadex G-75, and ion exchange chromatography through a CM-cellulose column. PMID:19547713

  14. Extremely high negative electron affinity of diamond via magnesium adsorption

    OpenAIRE

    O'Donnell, Kane M.; Edmonds, Mark T.; Tadich, Anton; Thomsen, Lars; Stacey, Alastair; Schenk, Alex; Pakes, Chris I.; Ley, Lothar

    2015-01-01

    We report large negative electron affinity (NEA) on diamond (100) using magnesium adsorption on a previously oxygen-terminated surface. The measured NEA is up to $(-2.01\\pm0.05)$ eV, the largest reported negative electron affinity to date. Despite the expected close relationship between the surface chemistry of Mg and Li species on oxygen-terminated diamond, we observe differences in the adsorption properties between the two. Most importantly, a high-temperature annealing step is not required...

  15. Combinatorial topology of three-dimensional self-affine tiles

    CERN Document Server

    Bandt, Christoph

    2010-01-01

    We develop tools to study the topology and geometry of self-affine fractals in dimension three and higher. We use the self-affine structure and obtain rather detailed information about the connectedness of interior and boundary sets, and on the dimensions and intersections of boundary sets. As an application, we describe in algebraic terms the polyhedral structure of the six fractal three-dimensional twindragons. Only two of them can be homeomorphic to a ball but even these have faces which are not homeomorphic to a disk.

  16. and as Vertex Operator Extensionsof Dual Affine Algebras

    Science.gov (United States)

    Bowcock, P.; Feigin, B. L.; Semikhatov, A. M.; Taormina, A.

    We discover a realisation of the affine Lie superalgebra and of the exceptional affine superalgebra as vertex operator extensions of two algebras with ``dual'' levels (and an auxiliary level-1 algebra). The duality relation between the levels is . We construct the representation of on a sum of tensor products of , , and modules and decompose it into a direct sum over the spectral flow orbit. This decomposition gives rise to character identities, which we also derive. The extension of the construction to is traced to the properties of embeddings into and their relation with the dual pairs. Conversely, we show how the representations are constructed from representations.

  17. SMOOTH AFFINE SURFACES WITH NON-UNIQUE C*-ACTIONS

    OpenAIRE

    Flenner, Hubert; Kaliman, Shulim; ZAIDENBERG, MIKHAIL

    2008-01-01

    In this paper we complete the classification of effective C*-actions on smooth affine surfaces up to conjugation in the full automorphism group and up to inversion of C*. If a smooth affine surface V admits more than one C*-action then it is known to be Gizatullin i.e., it can be completed by a linear chain of smooth rational curves. In our previous paper we gave a sufficient condition, in terms of the Dolgachev- Pinkham-Demazure (or DPD) presentation, for the uniqueness of a C*-action on a G...

  18. Algebraic volume density property of affine algebraic manifolds

    CERN Document Server

    Kaliman, Shulim

    2009-01-01

    We introduce the notion of algebraic volume density property for affine algebraic manifolds and prove some important basic facts about it, in particular that it implies the volume density property. The main results of the paper are producing two big classes of examples of Stein manifolds with volume density property. One class consists of certain affine modifications of $\\C^n$ equipped with a canonical volume form, the other is the class of all Linear Algebraic Groups equipped with the left invariant volume form.

  19. Affine diffusions and related processes simulation, theory and applications

    CERN Document Server

    Alfonsi, Aurélien

    2015-01-01

    This book gives an overview of affine diffusions, from Ornstein-Uhlenbeck processes to Wishart processes and it considers some related diffusions such as Wright-Fisher processes. It focuses on different simulation schemes for these processes, especially second-order schemes for the weak error. It also presents some models, mostly in the field of finance, where these methods are relevant and provides some numerical experiments. The book explains the mathematical background to understand affine diffusions and analyze the accuracy of the schemes.  

  20. Double affine Hecke algebras and 2-dimensional local fields

    OpenAIRE

    Kapranov, M.

    1998-01-01

    We give an interpretation of the double affine Hecke algebra of Cherednik as the (suitably regularized) algebra of double cosets of a group G by a subgroup J, extending the well known interpretations of finite and affine Hecke algebras. In this interpretation, G consists of K-points of a split reductive group where K is a 2-dimensional local field such as Q_p((t)) or F_q((t_1))((t_2)), and J is a certain analog of the Iwahori subgroup.

  1. Affinity based and molecularly imprinted cryogels: Applications in biomacromolecule purification.

    Science.gov (United States)

    Andaç, Müge; Galaev, Igor Yu; Denizli, Adil

    2016-05-15

    The publications in macro-molecularly imprinted polymers have increased drastically in recent years with the development of water-based polymer systems. The macroporous structure of cryogels has allowed the use of these materials within different applications, particularly in affinity purification and molecular imprinting based methods. Due to their high selectivity, specificity, efficient mass transfer and good reproducibility, molecularly imprinted cryogels (MICs) have become attractive for researchers in the separation and purification of proteins. In this review, the recent developments in affinity based cryogels and molecularly imprinted cryogels in protein purification are reviewed comprehensively. PMID:26454622

  2. Kinetic controlled affinity labeling of target enzyme with thioester chemistry.

    Science.gov (United States)

    Tomohiro, Takenori; Nakabayashi, Masahiro; Sugita, Yuka; Morimoto, Shota

    2016-08-01

    High specificity has been an important feature in affinity labeling for target profiling. Especially, to label targets via rapidly progressing reactions with consumption of ligand (probe), high specificity of reaction with common functional groups of target protein should be achieved without reactions with similar groups of non-target proteins. Herein, we demonstrate the kinetic controlled affinity labeling of acyl CoA synthetase using a fatty acid analogue containing a phenylthioester linkage. High specificity was attained by accelerating the labeling rate in the binding pocket. This approach could be useful for profiling a series of target enzymes and transporters in signal transduction pathways. PMID:27298000

  3. Affine Hecke algebras associated to Kac-Moody groups

    CERN Document Server

    Garland, H

    1995-01-01

    In this paper we give a geometric construction of Cherednik's double affine Hecke algebra. We construct the algebra as the equivariant K-theory of the Lagrangian subvariety of the cotangent variety of the square of the flag variety of G, the variety being given by the union of the conormal bundles to the G-orbits on \\flag\\times\\flag. This is a generalisation of work of Kazhdan and Lusztig to the Kac-Moody case, and is suitable for describing a certain class of modules for this algebra. In a paper in preparation we will do this, in the case G is affine (Cherednik's case).

  4. Multiple poes and other features of affine Toda field theory

    International Nuclear Information System (INIS)

    Some perturbative features of affine Toda field theory are explored, in particular the mechanisms responsible for the first-, second- and third-order poles in the conjectured exact factorisable S-matrices in the ADE series of models. It is found that generic collections of Feynman diagrams are responsible for the leading order poles in any of the theories. However, the complexity is such that it has not yet proved possible to analyse all the singularities that occur up to order twelve. Some comments are made on an associated tiling problem and on an interesting connection between the affine Toda couplings and the Clebsch-Gordan decomposition of tensor products. (orig.)

  5. Fertility in the Age of Demographic Maturity: An Essay

    Directory of Open Access Journals (Sweden)

    Anatole Romaniuk

    2010-01-01

    Full Text Available As humanity is moving into a new age of its demographic evolution, I call it demographic maturity, the emerging demographic configurations – generational sub-replacement fertility, advanced aging and potential population implosion – call for new ways of thinking about population and new policy approaches. While we live longer and healthier, we also reproduce less and less. We are stuck in a culture of low fertility. The strong motivations for foregoing motherhood are financial: a two-salary wage is better than one even for the higher middle class. No less important is the woman’s financial independence in a societal environment where marriage as an institution is under considerable stress. Motherhood is to be rewarded adequately for its highly important social role and it has to be sufficient to reassure potential mothers of their financial concerns. What is required is a more balanced resource allocation between production and reproduction. The old welfare type hand-outs like child bonuses do not work. Societies, particularly the rich, ought to realize that to raise fertility, even to generational replacement level, not only is a much greater financial effort called for but some of the tenants of the liberal economy need to be put into question to make room for social concerns such a renewal of generations, if they want to survive as national entities. This essay advocates a stationary population as the best response to challenges such as ecological health, national identity and cohesion, and possibly world peace.

  6. Characterization of the ER-Targeted Low Affinity Ca2+ Probe D4ER

    Directory of Open Access Journals (Sweden)

    Elisa Greotti

    2016-09-01

    Full Text Available Calcium ion (Ca2+ is a ubiquitous intracellular messenger and changes in its concentration impact on nearly every aspect of cell life. Endoplasmic reticulum (ER represents the major intracellular Ca2+ store and the free Ca2+ concentration ([Ca2+] within its lumen ([Ca2+]ER can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca2+ sensors have been developed over the last years. However, most of them are non-ratiometric and, thus, their signal is difficult to calibrate in live cells and is affected by shifts in the focal plane and artifactual movements of the sample. On the other hand, existing ratiometric Ca2+ probes are plagued by different drawbacks, such as a double dissociation constant (Kd for Ca2+, low dynamic range, and an affinity for the cation that is too high for the levels of [Ca2+] in the ER lumen. Here, we report the characterization of a recently generated ER-targeted, Förster resonance energy transfer (FRET-based, Cameleon probe, named D4ER, characterized by suitable Ca2+ affinity and dynamic range for monitoring [Ca2+] variations within the ER. As an example, resting [Ca2+]ER have been evaluated in a known paradigm of altered ER Ca2+ homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer’s Disease-linked protein Presenilin 2 (PS2. The lower Ca2+ affinity of the D4ER probe, compared to that of the previously generated D1ER, allowed the detection of a conspicuous, more clear-cut, reduction in ER Ca2+ content in cells expressing mutated PS2, compared to controls.

  7. Elastic Wave Propagation and Generation in Seismology

    Science.gov (United States)

    Lees, Jonathan M.

    The majority of mature seismologists of my generation were introduced to theoretical seismology via classic textbooks written in the early 1980s. Since this generation has matured and taken the mantle of teaching seismology to a new generation, several new books have been put forward as replacements, or alternatives, to the original classical texts. The target readers of the new texts range from beginner through intermediate to more advanced, although all have been attempts to improve upon what is now considered standard convention in quantitative seismology. To this plethora of choices we now have a new addition by Jose Pujol, titledElastic Wave Propagation and Generation in Seismology.

  8. A Comment on a Novel Approach for the Registration of Weak Affine Images

    Czech Academy of Sciences Publication Activity Database

    Flusser, Jan; Zitová, Barbara

    2013-01-01

    Roč. 34, č. 12 (2013), s. 1381-1385. ISSN 0167-8655 R&D Projects: GA ČR GAP103/11/1552 Keywords : Image registration * Affine transform * Affine subgroups * Weak affine transform * Area-preserving affine transform Subject RIV: JD - Computer Applications, Robotics Impact factor: 1.062, year: 2013 http://library.utia.cas.cz/separaty/2013/ZOI/flusser-a comment on a novel approach for the registration of weak affine images.pdf

  9. Obesity and secondary sexual maturity in boys

    Directory of Open Access Journals (Sweden)

    Modella Rahmani Femina

    2013-09-01

    Full Text Available Background Obesity induces earlier secondary sexual maturity in girls. However, results of studies in boys have been inconclusive. Objective To assess for an association between obesity and sexual maturity in boys. Methods This was a prospective cohort study on 133 obese and 133 matched-for-age, non-obese, prepubertal boys, aged 9 to 10 years. They were observed every 4 months for a two year period. Obesity was defined as the BMI ≥the 95th percentile, according to the Centers for Disease Control 2000 growth charts. Secondary sexual maturity was defined as testicular volume of ≥4 mL and Tanner staging of pubic hair of ≥P2. Two trained nurses and a pediatric resident collected the data. Results By the end of the study period, 106 (79.7% obese boys had attained a testicular volume of 4 mL or more, vs. 85 (63.9% non-obese boys (RR 1.78; 95%CI 1.19 to 2.67; P=0.004. Furthermore, 81 (60.9% obese boys attained pubic hair states of Tanner stage P2 vs. 37 (27.8% non-obese boys (RR 1.85 95%CI 1.46 to 2.34; P<0.001. The mean durations for achieving testicular volume of ≥4 mL were 21.25 (95%CI 20.75 to 21.74 months in obese boys and 22.26 (95%CI 21.80 to 22.72 months in non-obese boys (P=0.007. The mean durations for achieving Tanner stage P2 were 17.04 (95%CI 16.44 to 17.63 months in obese boys and 20.87 (95%CI 20.05 to 21.68 months in non-obese boys. Conclusion Obesity is associated with earlier onset of sexual maturity in boys. [Paediatr Indones. 2013;53:283-6.].

  10. The Homo Energeticus: maturity, inheritance, identity

    International Nuclear Information System (INIS)

    In this letter, modern society’s intimate bond to the convenience and reliability of delivered energy services results in a form of identification I call the Homo Energeticus. The Homo Energeticus relies upon a mature system of services for achieving an equivalency of status and prestige that is historically similar to the morality of a noble class. I describe the uniqueness of this identity by its imperative for acquiring experience through an invisibility of energy expenditures. In this way, the Homo Energeticus cultivates a highly individualized life whose ambience of perfection, while created personally, is only successful insofar as it conceals energy expenditures in labor and supply. (letter)

  11. eBusiness Maturity and Regional Development

    Directory of Open Access Journals (Sweden)

    Beynon-Davies, P.

    2007-01-01

    Full Text Available This paper describes the experience of a major research centre supporting knowledge transfer in the area of eCommerce to SMEs. It debates with issues surrounding the integration of academic research with practical support to the SME community. For this purpose the use of an eBusiness framework as a platform for eBusiness maturity assessment is proposed. These devices are seen as key to the work of research centres such as ours in addressing the future challenges for smeeBusiness.

  12. eBusiness Maturity and Regional Development

    OpenAIRE

    Beynon-Davies, P.

    2007-01-01

    This paper describes the experience of a major research centre supporting knowledge transfer in the area of eCommerce to SMEs. It debates with issues surrounding the integration of academic research with practical support to the SME community. For this purpose the use of an eBusiness framework as a platform for eBusiness maturity assessment is proposed. These devices are seen as key to the work of research centres such as ours in addressing the future challenges for smeeBusiness.

  13. Does a Mature AIDS Epidemic Threaten Growth?

    OpenAIRE

    Cuesta, José

    2008-01-01

    This paper models the impact on economic growth of HIV/AIDS when the epidemic is in a mature phase, in contrast with previous studies focused on periods of expansion, as in African countries. Simulations for Honduras, the epicenter of the epidemic in Central America, show that AIDS is not likely to threaten economic growth through either labor or capital accumulation channels; impacts are estimated between 0. 007 and 0. 27 percent points of GDP growth annually for the period 2001-10. Likewise...

  14. Asset Stripping in a Mature Market Economy

    DEFF Research Database (Denmark)

    Klarskov Jeppesen, Kim; Møller, Ulrik Gorm

    2011-01-01

    Purpose – The purpose of this paper is to document a Danish fraud scheme, in which a large number of limited companies were stripped of their assets leaving them with nothing but tax debt, eventually causing the Danish Tax and Customs Administration to lose large sums. Furthermore, the purpose...... indicates that asset stripping may take place in mature market economies to the extent that perpetrators are able to circumvent the corporate governance system by giving lawyers, public accountants and banks incentives to act less critically towards dubious business transactions. Research limitations...

  15. Petroleum maturation modelling, Abu Gabra Sharaf area, Muglad Basin, Sudan

    Science.gov (United States)

    Mohamed, Abdalla Y.; Pearson, Michael J.; Ashcroft, William A.; Whiteman, A. J.

    2002-08-01

    Structural and maturation studies in the northwest of the Muglad Basin, Sudan showed a thick sedimentary section up to 9000 m in the deep sub-basins and an average of about 6000 m in the Sharaf-Abu Gabra Ridge. The isopach map of the Lower Cretaceous Abu Gabra-Sharaf formations, which contain source rocks, showed a thickness of sedimentary section between 2000 and 5000 m. The burial history showed high subsidence rates during the first rifting phase with relatively low subsidence rates during the following two phases in this part of the basin. Significant erosion of the sedimentary section occurred in the ridge area during Miocene and Cenomanian-Albian times. The geothermal gradients in the modelled wells range between 18 and 27.5 °C/km corresponding to the relatively wide range of present day heat flow of between 37 and 63 mW/m 2, averaging 50 mW/m 2. Heat flow history curves consistent with vitrinite reflectance data were adopted with elevated high heat flow (75 mW/m 2) during the first rifting phase followed by minor peaks (average 60 mW/m 2) during the second and the third rifting phases. Application of a kinetic vitrinite maturation model resulted in a present day oil window between 2000 and 4500 m. The source rock of the Abu Gabra (AG) and Sharaf (SH) formations, which has an average total organic carbon of 1.0% and hydrogen index (HI) of 280, was modelled for hydrocarbon generation. The section was divided into four layers; AG-1 (Albian), AG-2 (Aptian), SH-1 (Barremian) and SH-2 (Neocomian). Conditions for hydrocarbon generation are present throughout the Sharaf formation and in AG-2. The generation model suggests an average generation amount of 4 mgHC/g rock in the lower three modelled layers with a timing range between 120 Ma and the present. Total calculated oil volume is about 370 US billion bbls and the expected volume expelled and migrated (40%) is 150 US billion bbls. The total gas expelled and migrated (90%) is 1600 US trillion cu ft. Retention of

  16. Maturation Rate of Ovine Oocytes from Different Reproductive Status and Maturation Medium

    OpenAIRE

    ARIEF BOEDIONO; YULNAWATI; MOHAMAD AGUS SETIADI

    2006-01-01

    The aim of the present study was to determine the number of follicles, oocyte quality and maturation rate of oocytes from pairs of ovary with different reproductive status in two maturation medium, TCM-199 as control and CR1aa as treatment. The pairs of ovary were classified into four groups: (i) ovaries with corpus luteum (CL) and dominant follicle (DF), (ii) ovaries with CL, without DF, (iii) ovaries with DF, without CL, (iv) ovaries without both CL and DF. Results of the experiment reveale...

  17. TOPICAL REVIEW: Braided affine geometry and q-analogs of wave operators

    Science.gov (United States)

    Gurevich, Dimitri; Saponov, Pavel

    2009-08-01

    The main goal of this review is to compare different approaches to constructing the geometry associated with a Hecke type braiding (in particular, with that related to the quantum group Uq(sl(n))). We place emphasis on the affine braided geometry related to the so-called reflection equation algebra (REA). All objects of such a type of geometry are defined in the spirit of affine algebraic geometry via polynomial relations on generators. We begin by comparing the Poisson counterparts of 'quantum varieties' and describe different approaches to their quantization. Also, we exhibit two approaches to introducing q-analogs of vector bundles and defining the Chern-Connes index for them on quantum spheres. In accordance with the Serre-Swan approach, the q-vector bundles are treated as finitely generated projective modules over the corresponding quantum algebras. Besides, we describe the basic properties of the REA used in this construction and compare different ways of defining q-analogs of partial derivatives and differentials on the REA and algebras close to them. In particular, we present a way of introducing a q-differential calculus via Koszul type complexes. The elements of the q-calculus are applied to defining q-analogs of some relativistic wave operators.

  18. High affinity mouse-human chimeric Fab against Hepatitis B surface antigen

    Institute of Scientific and Technical Information of China (English)

    Biplab Bose; Navin Khanna; Subrat K Acharya; Subrata Sinha

    2005-01-01

    AIM: Passive immunotherapy using antibody against hepatitis B surface antigen (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had earlier reported on the cloning and expression of a high affinity scFv derived from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be used for therapeutic purposes as it may elicit anti-mouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody.METHODS: We cloned the VH and VL genes of this mouse antibody; and fused them with CH1 domain of human IgG1 and CL domain of human kappa chain respectively. These chimeric genes were cloned into a phagemid vector. After initial screening using the phage display system, the chimeric Fab was expressed in soluble form in E. Coli.RESULTS: The chimeric Fab was purified from the bacterial periplasmic extract. We characterized the chimeric Fab using several in vitro techniques and it was observed that the chimeric molecule retained the high affinity and specificity of the original mouse monoclonal.This chimeric antibody fragment was further expressed in different strains of E> coli to increase the yield.CONCLUSION: We have generated a mouse-human chimeric Fab against HBsAg without any significant loss in binding and epitope specificity. This chimeric Fab fragment can be further modified to generate a fulllength chimeric antibody for therapeutic uses.

  19. Validation of the Psychological Work Maturity Scale in Chinese employees.

    Science.gov (United States)

    Tong, Jiajin; Wang, Lei

    2010-12-01

    Psychological work maturity is an important concept in situational leadership theory. The present research revised the Psychological Work Maturity Scale for use in Chinese organizations. Three samples of full-time employees (Ns = 205, 266, and 283) from different companies and industries participated in the present study. Confirmatory factor analysis showed that a single-factor structure fit the data. The scale had acceptable reliabilities, convergent and criterion-related validities, and was shown to be an appropriate measure of psychological work maturity in Chinese employees. Maturity differences in several demographic variables were not found, but employees with longer tenure in Sample 2 scored higher on maturity, which shows that psychological work maturity may be dependent on personal development in the interaction with the varying situational factors, especially in the work domain. Implications for research and practice on psychological work maturity in China are discussed. PMID:21323139

  20. Maturation arrest of human oocytes at germinal vesicle stage

    Directory of Open Access Journals (Sweden)

    Zhi Qin Chen

    2010-01-01

    Full Text Available Maturation arrest of human oocytes may occur at various stages of the cell cycle. A total failure of human oocytes to complete meiosis is rarely observed during assisted conception cycles. We describe here a case of infertile couples for whom all oocytes repeatedly failed to mature at germinal vesicle (GV stage during in vitro fertilization/Intra cytoplasmic sperm injection (IVF/ICSI. The patient underwent controlled ovarian stimulation followed by oocyte retrieval and IVF/ICSI. The oocytes were stripped off cumulus cells prior to the ICSI procedure and their maturity status was defined. The oocyte maturation was repeatedly arrested at the GV. Oocyte maturation arrest may be the cause of infertility in this couple. The recognition of oocyte maturation arrest as a specific medical condition may contribute to the characterization of the currently known as "oocyte factor." The cellular and genetic mechanisms causing oocyte maturation arrest should be the subject for further investigation.