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Sample records for affinity maturation generates

  1. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    linker for yeast surface display of scFv and scFab fragments, we compared a series of different Gly-Ser-based linkers in display and antigen binding proficiency. We show that these formats of the model antibody can accommodate linkers of different lengths and that introduction of alanine or glutamate......-2. Based on the presented data we suggest that affinity maturation of the model antibody proceeds through multiple incremental steps of subtle improvements. We moreover conclude that the best affinity improved candidates are likely to be obtained through optimization of both the antigen...... fragments by in vivo homologous recombination large combinatorial antibody libraries can easily be generated. We have optimized ordered assembly of three CDR fragments into a gapped vector and observed increased transformation efficiency in a yeast strain carrying a deletion of the SGS1 helicase...

  2. Affinity maturation generates greatly improved xyloglucan-specific carbohydrate binding modules

    Directory of Open Access Journals (Sweden)

    Cicortas Gunnarsson Lavinia

    2009-10-01

    Full Text Available Abstract Background Molecular evolution of carbohydrate binding modules (CBM is a new approach for the generation of glycan-specific molecular probes. To date, the possibility of performing affinity maturation on CBM has not been investigated. In this study we show that binding characteristics such as affinity can be improved for CBM generated from the CBM4-2 scaffold by using random mutagenesis in combination with phage display technology. Results Two modified proteins with greatly improved affinity for xyloglucan, a key polysaccharide abundant in the plant kingdom crucial for providing plant support, were generated. Both improved modules differ from other existing xyloglucan probes by binding to galactose-decorated subunits of xyloglucan. The usefulness of the evolved binders was verified by staining of plant sections, where they performed better than the xyloglucan-binding module from which they had been derived. They discriminated non-fucosylated from fucosylated xyloglucan as shown by their ability to stain only the endosperm, rich in non-fucosylated xyloglucan, but not the integument rich in fucosylated xyloglucan, on tamarind seed sections. Conclusion We conclude that affinity maturation of CBM selected from molecular libraries based on the CBM4-2 scaffold is possible and has the potential to generate new analytical tools for detection of plant carbohydrates.

  3. 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

  4. 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.

  5. 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...

  6. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies.

    Science.gov (United States)

    Briney, Bryan; Sok, Devin; Jardine, Joseph G; Kulp, Daniel W; Skog, Patrick; Menis, Sergey; Jacak, Ronald; Kalyuzhniy, Oleksandr; de Val, Natalia; Sesterhenn, Fabian; Le, Khoa M; Ramos, Alejandra; Jones, Meaghan; Saye-Francisco, Karen L; Blane, Tanya R; Spencer, Skye; Georgeson, Erik; Hu, Xiaozhen; Ozorowski, Gabriel; Adachi, Yumiko; Kubitz, Michael; Sarkar, Anita; Wilson, Ian A; Ward, Andrew B; Nemazee, David; Burton, Dennis R; Schief, William R

    2016-09-01

    Induction of broadly neutralizing antibodies (bnAbs) is a primary goal of HIV vaccine development. VRC01-class bnAbs are important vaccine leads because their precursor B cells targeted by an engineered priming immunogen are relatively common among humans. This priming immunogen has demonstrated the ability to initiate a bnAb response in animal models, but recall and maturation toward bnAb development has not been shown. Here, we report the development of boosting immunogens designed to guide the genetic and functional maturation of previously primed VRC01-class precursors. Boosting a transgenic mouse model expressing germline VRC01 heavy chains produced broad neutralization of near-native isolates (N276A) and weak neutralization of fully native HIV. Functional and genetic characteristics indicate that the boosted mAbs are consistent with partially mature VRC01-class antibodies and place them on a maturation trajectory that leads toward mature VRC01-class bnAbs. The results show how reductionist sequential immunization can guide maturation of HIV bnAb responses. PMID:27610570

  7. 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.

  8. 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;

    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 relate...

  9. 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.

  10. 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

  11. 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

  12. 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...

  13. 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

  14. Quantized Affine Lie Algebras and Diagonalization of Braid Generators

    CERN Document Server

    Gould, M D; Gould, Mark D.; Zhang, Yao-Zhong

    1994-01-01

    Let $U_q(\\hat{\\cal G})$ be a quantized affine Lie algebra. It is proven that the universal R-matrix $R$ of $U_q(\\hat{\\cal G})$ satisfies the celebrated conjugation relation $R^\\dagger=TR$ with $T$ the usual twist map. As applications, braid generators are shown to be diagonalizable on arbitrary tensor product modules of integrable irreducible highest weight $U_q(\\hat{\\cal G})$-module and a spectral decomposition formula for the braid generators is obtained which is the generalization of Reshetikhin's and Gould's forms to the present affine case. Casimir invariants are constructed and their eigenvalues computed by means of the spectral decomposition formula. As a by-product, an interesting identity is found.

  15. Human single chain antibody to vascular endothelial growth factor: gene cloning, high-level expression, affinity maturation and bioactivity

    Institute of Scientific and Technical Information of China (English)

    阎锡蕴[1; 汤健[2; 吴小平[3; 王凤采[4; 李建生[5; 杨东玲[6

    2000-01-01

    Using antibody phage display technique, a human single chain antibody to vascular endothelial growth factor (VEGF) has been cloned. The antibody expression reached 45% of the total bacterial proteins. The purification and refolding of the antibody were completed in one step by using gel filtration chromatograph. ELISA analysis showed that the antibody not only specifically bound to human VEGF, but also competitively inhibited VEGF reacting with its receptors. In order to raise the affinity of the single chain antibody, its heavy chain variable region was randomly mutated using error-prone PCR and an antibody mutant library was constructed, from which a mutant with higher affinity was screened out. The three-dimensional structure and binding affinity of wild type and mutant antibody were compared. Our study provided a potential reagent for tumor angiogenic therapy and a significant model for antibody high-level expression and affinity maturation.

  16. Human single chain antibody to vascular endothelial growth factor:gene cloning, high-level expression, affinity maturation and bioactivity

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Using antibody phage display technique,a human single chain antibody to vascular endothelial growth factor (VEGF) has been cloned.The antibody expression reached 45% of the total bacterial proteins.The purification and refolding of the antibody were completed in one step by using gel filtration chromatograph.ELISA analysis showed that the antibody not only specifically bound to human VEGF,but also competitively inhibited VEGF reacting with its receptors.In order to raise the affinity of the single chain antibody,its heavy chain variable region was randomly mutated using error-prone PCR and an antibody mutant library was constructed,from which a mutant with higher affinity was screened out.The three-dimensional structure and binding affinity of wild type and mutant antibody were compared.Our study provided a potential reagent for tumor angiogenic therapy and a significant model for antibody high-level expression and affinity maturation.

  17. 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

  18. An evaluation method of hydrocarbon generating potential of highly mature and over-mature marine carbonate

    Institute of Scientific and Technical Information of China (English)

    程克明; 王兆云

    1997-01-01

    How to restore the residual organic carbon and residual hydrocarbon-generating potential is discussed based on the hydrocarbon degradability of source rock. The results indicate there is linear function relationship between the restoring coefficient of residual organic carbon (Kc) and the vitrinite reflectance (Ro% ) of various kinds of source rock, but the relationship is secondary functional between the restoring coefficient of residual hydrocarbon-generating potential (Ks) and the vitrinite reflectance (R0%). It is pointed out that Kc= (1 - Dresidual)/(1-Dprimary), Xs=Kc (Dprimary/Dresidual). The restoration of residual organic carbon and hydrocarbon-gen era ting potential of the Cambrian and Ordovician highly mature marine carbonate in the Tarim Basin and North China region shows that the lower limit value of hydrocarbon generating potential and the organic matter abundance of carbonate source rock are basically the same as that of clastic rock. The technical difficulty in hydrocarbon generating eva

  19. 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.

  20. 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

  1. 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 SNLs 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.

  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. 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).

  4. Affinity Maturation of Monoclonal Antibody 1E11 by Targeted Randomization in CDR3 Regions Optimizes Therapeutic Antibody Targeting of HER2-Positive Gastric Cancer.

    Science.gov (United States)

    Ko, Bong-Kook; Choi, Soyoung; Cui, Lei Guang; Lee, Young-Ha; Hwang, In-Sik; Kim, Kyu-Tae; Shim, Hyunbo; Lee, Jong-Seo

    2015-01-01

    Anti-HER2 murine monoclonal antibody 1E11 has strong and synergistic anti-tumor activity in HER2-overexpressing gastric cancer cells when used in combination with trastuzumab. We presently optimized this antibody for human therapeutics. First, the complementarity determining regions (CDRs) of the murine antibody were grafted onto human germline immunoglobulin variable genes. No difference in affinity and biological activity was observed between chimeric 1E11 (ch1E11) and humanized 1E11 (hz1E11). Next, affinity maturation of hz1E11 was performed by the randomization of CDR-L3 and H3 residues followed by stringent biopanning selection. Milder selection pressure favored the selection of more diverse clones, whereas higher selection stringency resulted in the convergence of the panning output to a smaller number of clones with improved affinity. Clone 1A12 had four amino acid substitutions in CDR-L3, and showed a 10-fold increase in affinity compared to the parental clone and increased potency in an in vitro anti-proliferative activity assay with HER2-overepxressing gastric cancer cells. Clone 1A12 inhibited tumor growth of NCI-N87 xenograft model with similar efficacy to trastuzumab alone, and the combination treatment of 1A12 and trastuzumab completely removed the established tumors. These results suggest that humanized and affinity matured monoclonal antibody 1A12 is a highly optimized molecule for future therapeutic development against HER2-positive tumors.

  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. Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3.

    Science.gov (United States)

    Ahmed, Mahiuddin; Cheng, Ming; Zhao, Qi; Goldgur, Yehuda; Cheal, Sarah M; Guo, Hong-fen; Larson, Steven M; Cheung, Nai-kong V

    2015-12-11

    B7-H3 (CD276) is both an inhibitory ligand for natural killer cells and T cells and a tumor antigen that is widely expressed among human solid tumors. Anti-B7-H3 mouse monoclonal antibody 8H9 has been successfully used for radioimmunotherapy for patients with B7-H3(+) tumors. We present the humanization, affinity maturation, and epitope mapping of 8H9 based on structure determination, modeling, and yeast display methods. The crystal structure of ch8H9 Fab fragment was solved to 2.5-Å resolution and used as a template for humanization. By displaying the humanized 8H9 single chain Fv (scFv) on the surface of yeast, the affinity was matured by sequential random mutagenesis and fluorescence-activated cell sorting. Six mutations (three in the complementarity-determining region and three in the framework regions) were identified and incorporated into an affinity-matured humanized 8H9 construct (hu8H9-6m) and an affinity-matured chimeric 8H9 construct (ch8H9-6m). The hu8H9-6m scFv had a 160-fold improvement in affinity (0.9 nm KD) compared with parental hu8H9 scFv (144 nm KD). The IgG formats of ch8H9-6m and hu8H9-6m (nanomolar to subnanomolar KD) had 2-9-fold enhancements in affinity compared with their parental forms, potent in vitro antibody-dependent cell-mediated cytotoxicity (0.1-0.3 μg/ml EC50), and high tumor uptake in mouse xenografts. Based on in silico docking studies and experimental validation, the molecular epitope of 8H9 was determined to be dependent on the FG loop of B7-H3, a region critical to its function in immunologic blockade and unique among anti-B7-H3 antibodies published to date. PMID:26487718

  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. Generation of recombinant antibodies to rat GABAA receptor subunits by affinity selection on synthetic peptides.

    Directory of Open Access Journals (Sweden)

    Sujatha P Koduvayur

    Full Text Available The abundance and physiological importance of GABAA receptors in the central nervous system make this neurotransmitter receptor an attractive target for localizing diagnostic and therapeutic biomolecules. GABAA receptors are expressed within the retina and mediate synaptic signaling at multiple stages of the visual process. To generate monoclonal affinity reagents that can specifically recognize GABAA receptor subunits, we screened two bacteriophage M13 libraries, which displayed human scFvs, by affinity selection with synthetic peptides predicted to correspond to extracellular regions of the rat α1 and β2 GABAA subunits. We isolated three anti-β2 and one anti-α1 subunit specific scFvs. Fluorescence polarization measurements revealed all four scFvs to have low micromolar affinities with their cognate peptide targets. The scFvs were capable of detecting fully folded GABAA receptors heterologously expressed by Xenopus laevis oocytes, while preserving ligand-gated channel activity. Moreover, A10, the anti-α1 subunit-specific scFv, was capable of detecting native GABAA receptors in the mouse retina, as observed by immunofluorescence staining. In order to improve their apparent affinity via avidity, we dimerized the A10 scFv by fusing it to the Fc portion of the IgG. The resulting scFv-Fc construct had a Kd of ∼26 nM, which corresponds to an approximately 135-fold improvement in binding, and a lower detection limit in dot blots, compared to the monomeric scFv. These results strongly support the use of peptides as targets for generating affinity reagents to membrane proteins and encourage investigation of molecular conjugates that use scFvs as anchoring components to localize reagents of interest at GABAA receptors of retina and other neural tissues, for studies of receptor activation and subunit structure.

  9. 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

  10. S-boxes generated using Affine Transformation giving Maximum Avalanche Effect

    Directory of Open Access Journals (Sweden)

    Kumara Shama

    2011-09-01

    Full Text Available The Advanced Encryption Standard (AES was published by National Institute of Standards and Technology (NIST in November 2001, to replace DES (Data Encryption Standard and Triple DES. The S-box(Substitution box used in AES is designed to be resistant to known cryptanalytic attacks [1][2]. The property of the S-box is that the output cannot be described as a simple mathematical function of the input. The S-box is designed to provide good avalanche effect. The Avalanche Criteria of S-box depends on the generator matrix A used in affine transformation to construct the S-box. This paper investigates the construction of Sboxes by affine transformation which satisfy maximum Avalanche Criteria.

  11. Affinity maturation of single-chain variable fragment specific for aflatoxin B(1) using yeast surface display.

    Science.gov (United States)

    Min, Won-Ki; Kim, Sung-Gun; Seo, Jin-Ho

    2015-12-01

    As aflatoxin B1 is one of the most toxic mycotoxins, it is important to detect and to quantify aflatoxin B1 accurately by immunological methods. To enhance aflatoxin B1-binding affinity of the single-chain variable fragment, yeast surface display technique combined with fluorescence-activated cell sorting was applied. A randomly mutated scFv library was subjected to 4 rounds of fluorescence-activated cell sorting, resulting in isolation of 5 scFv variants showing an affinity improvement compared to the parental wild type scFv. The best scFv with a 9-fold improvement in affinity for aflatoxin B1 exhibited similar specificity to the monoclonal antibody. Most of the mutations in scFv-M37 were located outside of the canonical antigen-contact loops, suggesting that its affinity improvement might be driven by an allosteric effect inducing scFv-M37 to form a more favorable binding pocket for aflatoxin B1 than the wild type scFv. PMID:26041237

  12. 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.

  13. 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.

  14. Manganese-induced integrin affinity maturation promotes recruitment of alpha V beta 3 integrin to focal adhesions in endothelial cells: evidence for a role of phosphatidylinositol 3-kinase and Src.

    Science.gov (United States)

    Dormond, Olivier; Ponsonnet, Lionel; Hasmim, Meriem; Foletti, Alessandro; Rüegg, Curzio

    2004-07-01

    Integrin activity is controlled by changes in affinity (i.e. ligand binding) and avidity (i.e. receptor clustering). Little is known, however, about the effect of affinity maturation on integrin avidity and on the associated signaling pathways. To study the effect of affinity maturation on integrin avidity, we stimulated human umbilical vein endothelial cells (HUVEC) with MnCl(2) to increase integrin affinity and monitored clustering of beta 1 and beta 3 integrins. In unstimulated HUVEC, beta 1 integrins were present in fibrillar adhesions, while alpha V beta 3 was detected in peripheral focal adhesions. Clustered beta 1 and beta 3 integrins expressed high affinity/ligand-induced binding site (LIBS) epitopes. MnCl(2)-stimulation promoted focal adhesion and actin stress fiber formation at the basal surface of the cells, and strongly enhanced mAb LM609 staining and expression of beta 3 high affinity/LIBS epitopes at focal adhesions. MnCl(2)-induced alpha V beta 3 clustering was blocked by a soluble RGD peptide, by wortmannin and LY294002, two pharmacological inhibitors of phosphatidylinositol 3-kinase (PI 3-K), and by over-expressing a dominant negative PI 3-K mutant protein. Conversely, over-expression of active PI 3-K and pharmacological inhibiton of Src with PP2 and CGP77675, enhanced basal and manganese-induced alpha V beta 3 clustering. Transient increased phosphorylation of protein kinase B/Akt, a direct target of PI 3K, occurred upon manganese stimulation. MnCl(2) did not alter beta 1 integrin distribution or beta1 high-affinity/LIBS epitope expression. Based on these results, we conclude that MnCl(2)-induced alpha V beta 3 integrin affinity maturation stimulates focal adhesion and actin stress fiber formation, and promotes recruitment of high affinity alpha V beta 3 to focal adhesions. Affinity-modulated alpha V beta 3 clustering requires PI3-K signaling and is negatively regulate by Src.

  15. Using a Capability Maturity Model to Build on the Generational Approach to Student Engagement Practices

    Science.gov (United States)

    Nelson, K.; Clarke, J.; Stoodley, I.; Creagh, T.

    2015-01-01

    The generational approach to conceptualising first-year student learning behaviour has made a useful contribution to understanding student engagement. It has an explicit focus on student behaviour and we suggest that a Capability Maturity Model interpretation may provide a complementary extension of that understanding as it builds on the…

  16. 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

  17. 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.

  18. Affinity maturation of a novel antagonistic human monoclonal antibody with a long VH CDR3 targeting the Class A GPCR formyl-peptide receptor 1.

    Science.gov (United States)

    Douthwaite, Julie A; Sridharan, Sudharsan; Huntington, Catherine; Hammersley, Jayne; Marwood, Rose; Hakulinen, Jonna K; Ek, Margareta; Sjögren, Tove; Rider, David; Privezentzev, Cyril; Seaman, Jonathan C; Cariuk, Peter; Knights, Vikki; Young, Joyce; Wilkinson, Trevor; Sleeman, Matthew; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

    2015-01-01

    Therapeutic monoclonal antibodies targeting G-protein-coupled receptors (GPCRs) are desirable for intervention in a wide range of disease processes. The discovery of such antibodies is challenging due to a lack of stability of many GPCRs as purified proteins. We describe here the generation of Fpro0165, a human anti-formyl peptide receptor 1 (FPR1) antibody generated by variable domain engineering of an antibody derived by immunization of transgenic mice expressing human variable region genes. Antibody isolation and subsequent engineering of affinity, potency and species cross-reactivity using phage display were achieved using FPR1 expressed on HEK cells for immunization and selection, along with calcium release cellular assays for antibody screening. Fpro0165 shows full neutralization of formyl peptide-mediated activation of primary human neutrophils. A crystal structure of the Fpro0165 Fab shows a long, protruding VH CDR3 of 24 amino acids and in silico docking with a homology model of FPR1 suggests that this long VH CDR3 is critical to the predicted binding mode of the antibody. Antibody mutation studies identify the apex of the long VH CDR3 as key to mediating the species cross-reactivity profile of the antibody. This study illustrates an approach for antibody discovery and affinity engineering to typically intractable membrane proteins such as GPCRs.

  19. 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.

  20. 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...

  1. 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

  2. High affinity IgM(+) memory B cells are generated through a germinal center-dependent pathway.

    Science.gov (United States)

    Hara, Yasushi; Tashiro, Yasuyuki; Murakami, Akikazu; Nishimura, Miyuki; Shimizu, Takeyuki; Kubo, Masato; Burrows, Peter D; Azuma, Takachika

    2015-12-01

    During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM(+) memory cells and that this process continues even after CSR is accomplished. PMID:26514429

  3. Overcoming the hurdles for a reproducible generation of human functionally mature reprogrammed neurons.

    Science.gov (United States)

    Broccoli, Vania; Rubio, Alicia; Taverna, Stefano; Yekhlef, Latefa

    2015-06-01

    The advent of cell reprogramming technologies has widely disclosed the possibility to have direct access to human neurons for experimental and biomedical applications. Human pluripotent stem cells can be instructed in vitro to generate specific neuronal cell types as well as different glial cells. Moreover, new approaches of direct neuronal cell reprogramming can strongly accelerate the generation of different neuronal lineages. However, genetic heterogeneity, reprogramming fidelity, and time in culture of the starting cells can still significantly bias their differentiation efficiency and quality of the neuronal progenies. In addition, reprogrammed human neurons exhibit a very slow pace in gaining a full spectrum of functional properties including physiological levels of membrane excitability, sustained and prolonged action potential firing, mature synaptic currents and synaptic plasticity. This delay poses serious limitations for their significance as biological experimental model and screening platform. We will discuss new approaches of neuronal cell differentiation and reprogramming as well as methods to accelerate the maturation and functional activity of the converted human neurons.

  4. Efficient and cost-effective generation of mature neurons from human induced pluripotent stem cells.

    Science.gov (United States)

    Badja, Cherif; Maleeva, Galyna; El-Yazidi, Claire; Barruet, Emilie; Lasserre, Manon; Tropel, Philippe; Binetruy, Bernard; Bregestovski, Piotr; Magdinier, Frédérique

    2014-12-01

    For years, our ability to study pathological changes in neurological diseases has been hampered by the lack of relevant models until the recent groundbreaking work from Yamanaka's group showing that it is feasible to generate induced pluripotent stem cells (iPSCs) from human somatic cells and to redirect the fate of these iPSCs into differentiated cells. In particular, much interest has focused on the ability to differentiate human iPSCs into neuronal progenitors and functional neurons for relevance to a large number of pathologies including mental retardation and behavioral or degenerative syndromes. Current differentiation protocols are time-consuming and generate limited amounts of cells, hindering use on a large scale. We describe a feeder-free method relying on the use of a chemically defined medium that overcomes the need for embryoid body formation and neuronal rosette isolation for neuronal precursors and terminally differentiated neuron production. Four days after induction, expression of markers of the neurectoderm lineage is detectable. Between 4 and 7 days, neuronal precursors can be expanded, frozen, and thawed without loss of proliferation and differentiation capacities or further differentiated. Terminal differentiation into the different subtypes of mature neurons found in the human brain were observed. At 6-35 days after induction, cells express typical voltage-gated and ionotrophic receptors for GABA, glycine, and acetylcholine. This specific and efficient single-step strategy in a chemically defined medium allows the production of mature neurons in 20-40 days with multiple applications, especially for modeling human pathologies.

  5. Organic-matter maturation and petroleum generation model in the Yinggehai and Qiongdongnan basins

    Institute of Scientific and Technical Information of China (English)

    郝芳; 李思田; 孙永传; 张启明

    1996-01-01

    The enhancement of organic-matter maturation and petroleum generation by the migration and accumulation of active hydrothermal fluids in the high thermal-gradient, strongly overpressured environments in the Yinggehai and Qiongdongnan basins is systematically demonstrated by combination of geological, geochemical analysis and basin modeling. The retardation of organic-matter thermal evolution by abnormal pore-pressure is recognized, its manifestation and dynamic mechanism are illustrated, and chemical kinetic modeling of the pressure retardation is carried out. On this basis, the model of organic-matter thermal evolution and petroleum generation in high thermal-gradient, strongly overpressured environments is summarized. A correct understanding of the effects of active hydrothermal fluids and abnormal pore-fluid pressures on organic-matter thermal evolution is of great theoretical and practical significance for thermal history analysis, basin modeling and petroleum resource evaluation.

  6. 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

  7. 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.

  8. Complexes of neutralizing and non-neutralizing affinity matured Fabs with a mimetic of the internal trimeric coiled-coil of HIV-1 gp41.

    Directory of Open Access Journals (Sweden)

    Elena Gustchina

    Full Text Available A series of mini-antibodies (monovalent and bivalent Fabs targeting the conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41 has been previously constructed and reported. Crystal structures of two closely related monovalent Fabs, one (Fab 8066 broadly neutralizing across a wide panel of HIV-1 subtype B and C viruses, and the other (Fab 8062 non-neutralizing, representing the extremes of this series, were previously solved as complexes with 5-Helix, a gp41 pre-hairpin intermediate mimetic. Binding of these Fabs to covalently stabilized chimeric trimers of N-peptides of HIV-1 gp41 (named (CCIZN363 or 3-H has now been investigated using X-ray crystallography, cryo-electron microscopy, and a variety of biophysical methods. Crystal structures of the complexes between 3-H and Fab 8066 and Fab 8062 were determined at 2.8 and 3.0 Å resolution, respectively. Although the structures of the complexes with the neutralizing Fab 8066 and its non-neutralizing counterpart Fab 8062 were generally similar, small differences between them could be correlated with the biological properties of these antibodies. The conformations of the corresponding CDRs of each antibody in the complexes with 3-H and 5-Helix are very similar. The adaptation to a different target upon complex formation is predominantly achieved by changes in the structure of the trimer of N-HR helices, as well as by adjustment of the orientation of the Fab molecule relative to the N-HR in the complex, via rigid-body movement. The structural data presented here indicate that binding of three Fabs 8062 with high affinity requires more significant changes in the structure of the N-HR trimer compared to binding of Fab 8066. A comparative analysis of the structures of Fabs complexed to different gp41 intermediate mimetics allows further evaluation of biological relevance for generation of neutralizing antibodies, as well as provides novel structural insights into immunogen

  9. SOX2+ cell population from normal human brain white matter is able to generate mature oligodendrocytes.

    Directory of Open Access Journals (Sweden)

    Jorge Oliver-De La Cruz

    Full Text Available 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.

  10. Generation of a novel high-affinity monoclonal antibody with conformational recognition epitope on human IgM.

    Science.gov (United States)

    Sarikhani, Sina; Mirshahi, Manouchehr; Gharaati, Mohammad Reza; Mirshahi, Tooran

    2010-11-01

    As IgM is the first isotype of antibody which appears in blood after initial exposure to a foreign antigen in the pattern of primary response, detection, and quantification of this molecule in blood seems invaluable. To approach these goals, generation, and characterization of a highly specific mAb (monoclonal antibody) against human IgM were investigated. Human IgM immunoglobulins were used to immunize Balb/c mice. Spleen cells taken from the immunized animals were fused with SP2/O myeloma cells using PEG (polyethylene glycol, MW 1450) as fusogen. The hybridomas were cultured in HAT containing medium and supernatants from the growing hybrids were screened by enzyme-linked immunosorbent assay (ELISA) using plates coated with pure human IgM and the positive wells were then cloned at limiting dilutions. The best clone designated as MAN-1, was injected intraperitoneally to some Pristane-injected mice. Anti-IgM mAb was purified from the animals' ascitic fluid by protein-G sepharose followed by DEAE-cellulose ion exchange chromatography. MAN-1 interacted with human IgM with a very high specificity and affinity. The purity of the sample was tested by SDS-PAGE and the affinity constant was measured (K(a) = 3.5 x 10(9)M(-1). Immunoblotting and competitive ELISA were done and the results showed that the harvested antibody recognizes a conformational epitope on the mu chain of human IgM and there was no cross-reactivity with other subclasses of immunoglobulins. Furthermore, isotyping test was done and the results showed the subclass of the obtained mAb which was IgG(1)kappa. PMID:20162378

  11. Allogeneic Mature Human Dendritic Cells Generate Superior Alloreactive Regulatory T Cells in the Presence of IL-15.

    Science.gov (United States)

    Litjens, Nicolle H R; Boer, Karin; Zuijderwijk, Joke M; Klepper, Mariska; Peeters, Annemiek M A; Prens, Errol P; Verschoor, Wenda; Kraaijeveld, Rens; Ozgur, Zeliha; van den Hout-van Vroonhoven, Mirjam C; van IJcken, Wilfred F J; Baan, Carla C; Betjes, Michiel G H

    2015-06-01

    Expansion of Ag-specific naturally occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloantigen-specific nTregs. A highly enriched nTreg fraction (CD4(+)CD25(bright)CD127(-) T cells) was alloantigen-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDCs), or PBMCs. The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the Treg-specific demethylation region of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4, and cytokines. In addition, the Ag-specific suppressive capacity of these expanded nTregs was tested. Allogeneic mature moDCs and skin-derived DCs were superior in inducing nTreg expansion compared with immature moDCs or PBMCs in an HLA-DR- and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2 could facilitate optimal mature moDC-induced nTreg expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (highly demethylated at the Treg-specific demethylation region within the FOXP3 gene and highly expressed of FOXP3, HELIOS, and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-γ, and TNF-α, but few IL-17-producing nTregs were found. Next-generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Human allogeneic mature moDCs are highly efficient stimulator cells, in the presence of exogenous IL-15, for expansion of stable alloantigen-specific nTregs with superior suppressive function. PMID:25917092

  12. 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...

  13. 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.

  14. 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.

  15. 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 ...

  16. 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...

  17. The Utility of Affine Variables and Affine Coherent States

    CERN Document Server

    Klauder, John R

    2011-01-01

    Affine coherent states are generated by affine kinematical variables much like canonical coherent states are generated by canonical kinematical variables. Although all classical and quantum formalisms normally entail canonical variables, it is shown that affine variables can serve equally well for many classical and quantum studies. This general purpose analysis provides tools to discuss two major applications: (1) the completely successful quantization of a nonrenormalizable scalar quantum field theory by affine techniques, in complete contrast to canonical techniques which only offer triviality; and (2) a formulation of the kinematical portion of quantum gravity that favors affine kinematical variables over canonical kinematical variables, and which generates a framework in which a favorable analysis of the constrained dynamical issues can take place. All this is possible because of the close connection between the affine and the canonical stories, while the few distinctions can be used to advantage when ap...

  18. 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

  19. Affinity enhancement of antibodies: how low-affinity antibodies produced early in immune responses are followed by high-affinity antibodies later and in memory B-cell responses.

    Science.gov (United States)

    Eisen, Herman N

    2014-05-01

    The antibodies produced initially in response to most antigens are high molecular weight (MW) immunoglobulins (IgM) with low affinity for the antigen, while the antibodies produced later are lower MW classes (e.g., IgG and IgA) with, on average, orders of magnitude higher affinity for that antigen. These changes, often termed affinity maturation, take place largely in small B-cell clusters (germinal center; GC) in lymphoid tissues in which proliferating antigen-stimulated B cells express the highly mutagenic cytidine deaminase that mediates immunoglobulin class-switching and sequence diversification of the immunoglobulin variable domains of antigen-binding receptors on B cells (BCR). Of the large library of BCR-mutated B cells thus rapidly generated, a small minority with affinity-enhancing mutations are selected to survive and differentiate into long-lived antibody-secreting plasma cells and memory B cells. BCRs are also endocytic receptors; they internalize and cleave BCR-bound antigen, yielding peptide-MHC complexes that are recognized by follicular helper T cells. Imperfect correlation between BCR affinity for antigen and cognate T-cell engagement may account for the increasing affinity heterogeneity that accompanies the increasing average affinity of antibodies. Conservation of mechanisms underlying mutation and selection of high-affinity antibodies over the ≈200 million years of evolution separating bird and mammal lineages points to the crucial role of antibody affinity enhancement in adaptive immunity.

  20. 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...

  1. Pancreatic Cancer Cells Isolated from Muc1-null Tumors Favor the Generation of a Mature Less Suppressive MDSC Population

    Directory of Open Access Journals (Sweden)

    Amritha eKidiyoor

    2014-02-01

    Full Text Available Mucin 1 (MUC1 is a transmembrane mucin glycoprotein that is over-expressed and aberrantly glycosylated in >80% of human pancreatic ductal adenocarcinoma (PDA and is associated with poor prognosis. To understand the role of MUC1 in PDA, we have recently developed two mouse models of spontaneous PDA, one that expresses full-length human MUC1 transgene (KCM mice and one that is null for MUC1 (KCKO mice. We have previously reported that KCM mice express high levels of myeloid derived suppressor cells (MDSCs in their tumors and develop highly aggressive PDA. To further understand the underlying mechanism for high MDSC levels in KCM tumors, we generated primary cell lines from KCM and KCKO tumors. In this study, we report that MDSCs derived using KCM cells express significantly higher levels of arginase 1 and inducible nitric oxide synthase (markers associated with immune suppression and lower levels of CD115 (a marker associated with maturation of myeloid cells as compared to KCKO-derived MDSCs. Functionally, KCM-derived MDSCs secrete significantly higher levels of urea and nitric oxide when co-cultured with normal splenic cells as compared to KCKO-derived MDSCs. Data indicates that KCM-derived MDSCs remain immature and are more suppressive as compared to KCKO-derived MDSCs. This was further corroborated in vivo where MDSCs isolated from KCM-tumor bearing mice retained their immature state and were highly suppressive as compared to MDSCs derived from KCKO-tumor bearing mice. Finally, we show that KCM cells secrete significantly higher levels of prostaglandin E2 (PGE2,, a COX-2 metabolite and a known driver of suppressive MDSCs as compared to KCKO cells. Thus, inhibiting PGE2 with a specific COX-2 inhibitor reverses the immunosuppressive and immature phenotype of KCM-derived MDSCs. This is the first report that clearly suggests a functional role of pancreatic tumor-associated MUC1 in the development of functional MDSCs.

  2. 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...

  3. A New 4.0-Generation Dendrimer Phosphorescence Labeling Reagent and Its Application to Determination of Trace Alkaline Phosphatase by Affinity Adsorption Solid Substrate-room Temperature Phosphorimetry

    Institute of Scientific and Technical Information of China (English)

    LI, Zhi-Ming; LIU, Jia-Ming; CHEN, Xiao-Hua; YANG, Min-Lan; CHEN, Xin-Hua; SHI, Xiu-Mei

    2007-01-01

    A Triton X-100-4.0G-D (4.0G-D refers to a 4.0-generation dendrimer) was brought forward as a new phosphorescence labeling reagent. Two types of specific affinity adsorption (AA) reactions (direct method and sandwich method) were carried out between the labeling product of Triton X-100-4.0G-D-Wheat germ agglutinin (WGA) and alkaline phosphatase (ALP), the product of AA reaction preserved the good characteristics of room temperature phosphorescence (RTP) of 4.0G-D and △Ip of the product was proportional to the content of ALP. According to the fact stated above, a new method for the determination of trace ALP by affinity adsorption solid substrate-room temperature phosphorimetry (AA-SS-RTP) was established on the basis of WGA labeled with the Triton X-100-4.0G-D. The detection limits were 0.20 ag·spot-1 (corresponding concentration: 5.0 × 10-16 g·mL-1, namely 5.0× 10-18 mol·L-1) for a direct method and 0.14 ag·spot-1 (corresponding concentration: 3.5× 10-16 g·mL-1,namely 3.5 × 10-18 mol·L-1) for a sandwich method, respectively. For their high sensitivity, good repeatability and high accuracy, the direct method and sandwich method have been successfully applied to determine the content of ALP in human serum, and the results were coincided with the clinical detection results of the enzyme-linked immunosorbent assay method by the Zhangzhou Hospital of Traditional Chinese Medicine. Meanwhile, the mechanism for the determination of trace ALP by AA-SS-RTP was discussed.

  4. 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…

  5. 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

  6. 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.

  7. On affine non-negative matrix factorization

    DEFF Research Database (Denmark)

    Laurberg, Hans; Hansen, Lars Kai

    2007-01-01

    We generalize the non-negative matrix factorization (NMF) generative model to incorporate an explicit offset. Multiplicative estimation algorithms are provided for the resulting sparse affine NMF model. We show that the affine model has improved uniqueness properties and leads to more accurate...

  8. 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.

  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. Affinization of category O for quantum groups

    CERN Document Server

    Young, C A S

    2012-01-01

    Let g be a simple Lie algebra. We consider the category O-hat of those modules over the affine quantum group Uq(g-hat) whose Uq(g)-weights have finite multiplicity and lie in a finite union of cones generated by negative roots. We show that many properties of the category of the finite-dimensional representations naturally extend to the category O-hat. In particular, we develop the theory of q-characters and define the minimal affinizations of parabolic Verma modules. In types ABCFG we classify these minimal affinizations and conjecture a Weyl denominator type formula for their characters.

  12. 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.

  13. 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 $\\bX$.

  14. 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.)

  15. 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.

  16. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

    Science.gov (United States)

    De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

    2016-06-01

    In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Fourth-generation epac-based FRET sensors for cAMP feature exceptional brightness, photostability and dynamic range: characterization of dedicated sensors for FLIM, for ratiometry and with high affinity.

    Directory of Open Access Journals (Sweden)

    Jeffrey Klarenbeek

    Full Text Available Epac-based FRET sensors have been widely used for the detection of cAMP concentrations in living cells. Originally developed by us as well as others, we have since then reported several important optimizations that make these sensors favourite among many cell biologists. We here report cloning and characterization of our fourth generation of cAMP sensors, which feature outstanding photostability, dynamic range and signal-to-noise ratio. The design is based on mTurquoise2, currently the brightest and most bleaching-resistant donor, and a new acceptor cassette that consists of a tandem of two cp173Venus fluorophores. We also report variants with a single point mutation, Q270E, in the Epac moiety, which decreases the dissociation constant of cAMP from 9.5 to 4 μM, and thus increases the affinity ~ 2.5-fold. Finally, we also prepared and characterized dedicated variants with non-emitting (dark acceptors for single-wavelength FLIM acquisition that display an exceptional near-doubling of fluorescence lifetime upon saturation of cAMP levels. We believe this generation of cAMP outperforms all other sensors and therefore recommend these sensors for all future studies.

  2. Affine stochastic mortality

    NARCIS (Netherlands)

    D.F. Schrager

    2006-01-01

    We propose a new model for stochastic mortality. The model is based on the literature on affine term structure models. It satisfies three important requirements for application in practice: analytical tractibility, clear interpretation of the factors and compatibility with financial option pricing m

  3. Production characters of first generation cows of a five-breed diallel: reproduction of mature cows and preweaning performance of calves by two third-breed sires.

    Science.gov (United States)

    McElhenney, W H; Long, C R; Baker, J F; Cartwright, T C

    1986-07-01

    The fourth through sixth parity of 5- to 10-yr-old cows were used to evaluate trade-offs involved with sires of large mature size vs medium mature size in a terminal sire crossbreeding program and to characterize five breeds and their crosses for their potential as dam lines. Charolais and Red Poll bulls, representing large (L) and medium (M) mature size, respectively, were mated to cows representing Angus (An), Brahman (Br), Hereford (He), Holstein (Ho) and Jersey (Je) and their crosses (reciprocals pooled). Cows were randomly assigned for mating to either an L or M bull for each breeding. Size of calf sire did not influence (P greater than .10) the subsequent calving interval of cows. Calving intervals for the straightbred (SB) dairy breeds (Ho and Je) were longer than for SB An and He, but the difference did not exist among the respective crossbred (CB) cows. As a group, Br crosses had shorter intervals than the other CB groups. Crossbred cows exhibited intervals that were 16 d shorter (P less than .05) than SB. Calves sired by L bulls were larger (P less than .01) and faster gaining (P less than .01) for all measures of size and growth studied, but exhibited lower (P less than .01) survival rates to weaning than M-sired calves. Calves of CB dams were 1.5 kg heavier (P less than .01) at birth than calves of SB dams and slightly greater (nonsignificant) hip and shoulder measurements were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3733578

  4. 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.

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Geochemical Characteristics and Hydrocarbon- Generating Mechanism of Low-Mature Shale Oil in Malang Sag%马朗凹陷低熟页岩油地球化学特征及成烃机理

    Institute of Scientific and Technical Information of China (English)

    吴红烛; 黄志龙; 杨柏松; 柳波; 闫玉魁; 桑廷义; 川江

    2014-01-01

    勘探实践和研究表明,马朗凹陷二叠系芦草沟组源内油气为页岩油,该原油C29甾烷立体异构化参数 w(20S)/w(20S+20R)、w(ββ)/w(αα+ββ)均为0.2~0.4,为典型低熟原油。通过对芦草沟组烃源岩地球化学和有机岩石学特征的综合研究,发现低熟页岩油的生烃母质为原生的富氢无定形体,这些无定形体在沉积早期经历过细菌的改造作用,致使其具有特殊的生烃演化模式,即低熟成熟阶段早期( Ro 为0.55%~0.75%)处于生油高峰,对应埋深为1800~2900 m ,埋深大于或小于该主峰带,烃源岩生烃能力急剧降低。泥岩生烃模拟实验、热解、抽提等实验数据表明:芦草沟组低熟页岩油正是位于该主生带的源岩所生,处于生烃带的源岩区即为马朗凹陷低熟页岩油富集的有利地区。%Exploration practices and researches show that hydrocarbon in the source rocks of the Lucaogou Formation of the Permian ,Malang sag was shale oil and also a typical low-mature oil with both sterane isomerization parameters (20S/(20S + 20R) and ββ/(αα + ββ)) between 0 .2 and 0 .4 . Through comprehensive study of geochemical and organic petrology characteristics in the hydrocarbon source rock of Lucaogou Formation ,we find that the parent material of this low-mature shale oil was hydrogen-rich amorphous solid and experienced the bacteria transformation in the early sedimentary stage , w hich resulted in the formation of the particular hydrocarbon-generating evolution model . Namely ,during the low-mature and early mature stage with Ro values 0 .55% 0 .75% ,there is an oil generation peak w hose burial depth ranges from 1 800 to 2 900 m , and the hydrocarbon-generating potential of source rock drops sharply beyond the main hydrocarbon-generating zone . The results of hydrocarbon-generating simulation experiments , rock pyrolysis analysis and organic extraction of mudstone

  13. 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.

  14. Affine morphisms at zero level

    CERN Document Server

    Das, Paramita; Gupta, Ved Prakash

    2010-01-01

    Given a finite index subfactor, we show that the {\\em affine morphisms at zero level} in the affine category over the planar algebra associated to the subfactor is isomorphic to the fusion algebra of the subfactor as a *-algebra.

  15. 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 $_{-p}K$.

  16. In vitro impact of bisphenols BPA, BPF, BPAF and 17β-estradiol (E2) on human monocyte-derived dendritic cell generation, maturation and function.

    Science.gov (United States)

    Švajger, Urban; Dolenc, Marija Sollner; Jeras, Matjaž

    2016-05-01

    Bisphenols (BPs) are widely spread pollutants that act as estrogen-like endocrine disruptors and are potentially affecting human health on a long run. We explored the effects of BPA, BPF and BPAF, on in vitro differentiation and maturation of MDDCs. Monocytes were treated with 17β-estradiol (E2) and each BP at the beginning of their differentiation into iMDDCs. We found that 10 and 50 μM of BPA and BPF, 10 and 30μM of BPAF and 10 and 50 nM of E2 did not affect cell viability. However, 50 μM of BPA and BPF, as well as 10 and 30 μM of BPAF, significantly decreased the endocytotic capacity of iMDDCs. Both, BPA (50 μM) and BPAF (30 μM) decreased the expression of CD1a and increased the amount of DC-SIGN molecules on iMDDCs. The E2 pre-treatment moderately decreased expression of CD80, CD86 and CD83 co-stimulatory molecules while increasing the numbers of HLA-DR on mMDDCs. Only BPAF significantly influenced the expression of CD80 and CD86 (both decreased), as well as CD83 and HLA-DR molecules (both increased) on mMDDCs. In addition, BPAF modulated DC maturation signaling pathways by lowering the phosphorylation of p65 NF-κB (nuclear factor-kappaB) and ERK (extracellular signal regulated kinase) 1/2 proteins. Consequently, the in vitro proliferation of allogeneic T cells, stimulated with differently pre-treated iMDDCs and mMDDCs, was significantly reduced only in case of BPAF. PMID:26945833

  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. Affine Patches on Positroid Varieties and Affine Pipe Dreams (Thesis)

    CERN Document Server

    Snider, Michelle

    2010-01-01

    The objects of interest in this thesis are positroid varieties in the Grassmannian, which are indexed by juggling patterns. In particular, we study affine patches on these positroid varieties. Our main result corresponds these affine patches to Kazhdan-Lusztig varieties in the affine Grassmannian. We develop a new term order and study how these spaces are related to subword complexes and Stanley-Reisner ideals. We define an extension of pipe dreams to the affine case and conclude by showing how our affine pipe dreams are generalizations of Cauchon and Le diagrams.

  19. Affine and quasi-affine frames for rational dilations

    DEFF Research Database (Denmark)

    Bownik, Marcin; Lemvig, Jakob

    2011-01-01

    , the corresponding family of quasi-affine systems are frames with uniform frame bounds. We also prove a similar equivalence result between pairs of dual affine frames and dual quasi-affine frames. Finally, we uncover some fundamental differences between the integer and rational settings by exhibiting an example......In this paper we extend the investigation of quasi-affine systems, which were originally introduced by Ron and Shen [J. Funct. Anal. 148 (1997), 408-447] for integer, expansive dilations, to the class of rational, expansive dilations. We show that an affine system is a frame if, and only if...

  20. Inhibiting HER3-mediated tumor cell growth with affibody molecules engineered to low picomolar affinity by position-directed error-prone PCR-like diversification.

    Science.gov (United States)

    Malm, Magdalena; Kronqvist, Nina; Lindberg, Hanna; Gudmundsdotter, Lindvi; Bass, Tarek; Frejd, Fredrik Y; Höidén-Guthenberg, Ingmarie; Varasteh, Zohreh; Orlova, Anna; Tolmachev, Vladimir; Ståhl, Stefan; Löfblom, John

    2013-01-01

    The HER3 receptor is implicated in the progression of various cancers as well as in resistance to several currently used drugs, and is hence a potential target for development of new therapies. We have previously generated Affibody molecules that inhibit heregulin-induced signaling of the HER3 pathways. The aim of this study was to improve the affinity of the binders to hopefully increase receptor inhibition efficacy and enable a high receptor-mediated uptake in tumors. We explored a novel strategy for affinity maturation of Affibody molecules that is based on alanine scanning followed by design of library diversification to mimic the result from an error-prone PCR reaction, but with full control over mutated positions and thus less biases. Using bacterial surface display and flow-cytometric sorting of the maturation library, the affinity for HER3 was improved more than 30-fold down to 21 pM. The affinity is among the higher that has been reported for Affibody molecules and we believe that the maturation strategy should be generally applicable for improvement of affinity proteins. The new binders also demonstrated an improved thermal stability as well as complete refolding after denaturation. Moreover, inhibition of ligand-induced proliferation of HER3-positive breast cancer cells was improved more than two orders of magnitude compared to the previously best-performing clone. Radiolabeled Affibody molecules showed specific targeting of a number of HER3-positive cell lines in vitro as well as targeting of HER3 in in vivo mouse models and represent promising candidates for future development of targeted therapies and diagnostics.

  1. 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.

  2. 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.

  3. European and international collaboration in affinity proteomics.

    Science.gov (United States)

    Stoevesandt, Oda; Taussig, Michael J

    2012-06-15

    In affinity proteomics, specific protein-binding molecules (a.k.a. binders), principally antibodies, are applied as reagents in proteome analysis. In recent years, advances in binder technologies have created the potential for an unprecedented view on protein expression and distribution patterns in plasma, cells and tissues and increasingly on protein function. Particular strengths of affinity proteomics methods include detecting proteins in their natural environments of cell or tissue, high sensitivity and selectivity for detection of low abundance proteins and exploiting binding actions such as functional interference in living cells. To maximise the use and impact of affinity reagents, it will be essential to create comprehensive, standardised binder collections. With this in mind, the EU FP7 programme AFFINOMICS (http://www.affinomics.org), together with the preceding EU programmes ProteomeBinders and AffinityProteome, aims to extend affinity proteomics research by generating a large-scale resource of validated protein-binding molecules for characterisation of the human proteome. Activity is directed at producing binders to about 1000 protein targets, primarily in signal transduction and cancer, by establishing a high throughput, coordinated production pipeline. An important aspect of AFFINOMICS is the development of highly efficient recombinant selection methods, based on phage, cell and ribosome display, capable of producing high quality binders at greater throughput and lower cost than hitherto. The programme also involves development of innovative and sensitive technologies for specific detection of target proteins and their interactions, and deployment of binders in proteomics studies of clinical relevance. The need for such binder generation programmes is now recognised internationally, with parallel initiatives in the USA for cancer (NCI) and transcription factors (NIH) and within the Human Proteome Organisation (HUPO). The papers in this volume of New

  4. 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.

  5. Generation of Interpersonal Stressful Events : The Role of Poor Social Skills and Early Physical Maturation in Young Adolescents-The TRAILS Study

    NARCIS (Netherlands)

    Bakker, Martin P.; Ormel, Johan; Lindenberg, Siegwart; Verhulst, Frank C.; Oldehinkel, Albertine J.

    2011-01-01

    This study developed two specifications of the social skills deficit stress generation hypothesis: the "gender-incongruence" hypothesis to predict peer victimization and the "need for autonomy" hypothesis to predict conflict with authorities. These hypotheses were tested in a prospective large popul

  6. Jacobi Structures on Affine Bundles

    Institute of Scientific and Technical Information of China (English)

    J. GRABOWSKI; D. IGLESIAS; J. C. MARRERO; E. PADR(O)N; P. URBA(N)SKI

    2007-01-01

    We study affine Jacobi structures (brackets) on an affine bundle π: A→M, i.e. Jacobi brackets that close on affine functions. We prove that if the rank of A is non-zero, there is a one-to- one correspondence between affine Jacobi structures on A and Lie algebroid structures on the vector bundle A+=∪p∈M Aff(Ap, R) of affine functionals. In the case rank A = 0, it is shown that there is a one-to-one correspondence between affins Jacobi structures on A and local Lie algebras on A+. Some examples and applications, also for the linear case, are discussed. For a special type of affine Jacobi structures which are canonically exhibited (strongly-affine or affine-homogeneous Jacobi structures) over a real vector space of finite dimension, we describe the leaves of its characteristic foliation as the orbits of an affine representation. These afline Jacobi structures can be viewed as an analog of the Kostant-Arnold-LiouviUe linear Poisson structure on the dual space of a real finite-dimensional Lie algebra.

  7. MATURE: A Model Driven bAsed Tool to Automatically Generate a langUage That suppoRts CMMI Process Areas spEcification

    Science.gov (United States)

    Musat, David; Castaño, Víctor; Calvo-Manzano, Jose A.; Garbajosa, Juan

    Many companies have achieved a higher quality in their processes by using CMMI. Process definition may be efficiently supported by software tools. A higher automation level will make process improvement and assessment activities easier to be adapted to customer needs. At present, automation of CMMI is based on tools that support practice definition in a textual way. These tools are often enhanced spreadsheets. In this paper, following the Model Driven Development paradigm (MDD), a tool that supports automatic generation of a language that can be used to specify process areas practices is presented. The generation is performed from a metamodel that represents CMMI. This tool, differently from others available, can be customized according to user needs. Guidelines to specify the CMMI metamodel are also provided. The paper also shows how this approach can support other assessment methods.

  8. 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.

  9. 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.

  10. 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.

  11. The Simulation Experiment on Gas-generating Potential of Over Mature Source Rocks%烃源岩过成熟阶段生气潜力的实验室模拟

    Institute of Scientific and Technical Information of China (English)

    王东良; 张英; 卢双舫; 国建英; 李志生; 莫午零; 王民; 王义凤

    2012-01-01

    源岩生气潜力的定量评价主要以实验室模拟为手段,由于技术条件的限制,模拟温度一般最高到600℃,认为生气能力已经耗尽,600%之前的生气量就可作为源岩生气潜力评价的定量依据。而对于60&E之后的生气潜力到底有没有?有多少?一直存在着争议。为了定量评价源岩过成熟阶段的生气潜力,我们通过技术开发将实验温度提高到了1000%,通过大量的实验结果发现,源岩在600—800℃之间仍然可以生成大量的天然气,煤系源岩的生气量占总生气量的20%~30%甚至更多,而湖相和海相源岩在这一阶段的生气量相对少一些,约占总生气量的10%,这与其干酪根的骨架结构不同密切相关。天然气生成下限的向下延伸,进一步扩大了过成熟阶段天然气的资源基础,对指导深层勘探有重要意义。%As for the gas-generating potential at the over-mature stage, the authors used the Rock-Eval rock pyrolog- get and TG-MS high-temperature pyrogenating simulated experiment device to carry out a series of experiment and re- search. By using the coal and carbonaceous mudstone of Jurassic in Junggar Basin and outcrop coal sample of the Per- mian system and Carboniferous carbonaceous mudstone in Ordos Basin, we carried out the gas-generating simulation experiment and the temperature is from 300℃ to 800℃. According to the result, all the rocks have generated a lot of gas when the temperature is lower than 600℃ (that is Ro 〈 2.0% -2.5 % ). When increasing the experiment temper- ature from 600℃ to 800℃, which means to raise Ro from 2.0% ~2.5% to 5.0%, we found that both the coal andthe carbonaceous mudstone in the two Basin can generate a great amount of natural gas between 600 - 800℃. The gas generated from the carboniferous carbonaceous mudstone accounts for 25.38%, 34.39%. The gas generated from the two type source rocks at the over-mature stage accounts

  12. 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

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Ching-Yi, E-mail: l2897107@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Taiwan (China); Ita, Eyo, E-mail: ita@usna.edu [Department of Physics, US Naval Academy, Annapolis, MD (United States); Soo, Chopin, E-mail: cpsoo@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Taiwan (China)

    2014-04-15

    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.

  15. Realization of Fractal Affine Transformation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper gives the definition of fractal affine transformation and presents a specific method for its realization and its cor responding mathematical equations which are essential in fractal image construction.

  16. 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

  17. 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.

  18. High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination.

    Directory of Open Access Journals (Sweden)

    Kaval Kaur

    Full Text Available Breakdown of B cell tolerance is a cardinal feature of systemic lupus erythematosus (SLE. Increased numbers of autoreactive mature naïve B cells have been described in SLE patients and autoantibodies have been shown to arise from autoreactive and non-autoreactive precursors. How these defects, in the regulation of B cell tolerance and selection, influence germinal center (GC reactions that are directed towards foreign antigens has yet to be investigated. Here, we examined the characteristics of post-GC foreign antigen-specific B cells from SLE patients and healthy controls by analyzing monoclonal antibodies generated from plasmablasts induced specifically by influenza vaccination. We report that many of the SLE patients had anti-influenza antibodies with higher binding affinity and neutralization capacity than those from controls. Although overall frequencies of autoreactivity in the influenza-specific plasmablasts were similar for SLE patients and controls, the variable gene repertoire of influenza-specific plasmablasts from SLE patients was altered, with increased usage of JH6 and long heavy chain CDR3 segments. We found that high affinity anti-influenza antibodies generally characterize the plasmablast responses of SLE patients with low levels of autoreactivity; however, certain exceptions were noted. The high-avidity antibody responses in SLE patients may also be correlated with cytokines that are abnormally expressed in lupus. These findings provide insights into the effects of dysregulated immunity on the quality of antibody responses following influenza vaccination and further our understanding of the underlying abnormalities of lupus.

  19. High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination

    Science.gov (United States)

    Kaur, Kaval; Zheng, Nai-Ying; Smith, Kenneth; Huang, Min; Li, Lie; Pauli, Noel T.; Henry Dunand, Carole J.; Lee, Jane-Hwei; Morrissey, Michael; Wu, Yixuan; Joachims, Michelle L.; Munroe, Melissa E.; Lau, Denise; Qu, Xinyan; Krammer, Florian; Wrammert, Jens; Palese, Peter; Ahmed, Rafi; James, Judith A.; Wilson, Patrick C.

    2015-01-01

    Breakdown of B cell tolerance is a cardinal feature of systemic lupus erythematosus (SLE). Increased numbers of autoreactive mature naïve B cells have been described in SLE patients and autoantibodies have been shown to arise from autoreactive and non-autoreactive precursors. How these defects, in the regulation of B cell tolerance and selection, influence germinal center (GC) reactions that are directed towards foreign antigens has yet to be investigated. Here, we examined the characteristics of post-GC foreign antigen-specific B cells from SLE patients and healthy controls by analyzing monoclonal antibodies generated from plasmablasts induced specifically by influenza vaccination. We report that many of the SLE patients had anti-influenza antibodies with higher binding affinity and neutralization capacity than those from controls. Although overall frequencies of autoreactivity in the influenza-specific plasmablasts were similar for SLE patients and controls, the variable gene repertoire of influenza-specific plasmablasts from SLE patients was altered, with increased usage of JH6 and long heavy chain CDR3 segments. We found that high affinity anti-influenza antibodies generally characterize the plasmablast responses of SLE patients with low levels of autoreactivity; however, certain exceptions were noted. The high-avidity antibody responses in SLE patients may also be correlated with cytokines that are abnormally expressed in lupus. These findings provide insights into the effects of dysregulated immunity on the quality of antibody responses following influenza vaccination and further our understanding of the underlying abnormalities of lupus. PMID:25951191

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. A thermodynamic approach to the affinity optimization of drug candidates.

    Science.gov (United States)

    Freire, Ernesto

    2009-11-01

    High throughput screening and other techniques commonly used to identify lead candidates for drug development usually yield compounds with binding affinities to their intended targets in the mid-micromolar range. The affinity of these molecules needs to be improved by several orders of magnitude before they become viable drug candidates. Traditionally, this task has been accomplished by establishing structure activity relationships to guide chemical modifications and improve the binding affinity of the compounds. As the binding affinity is a function of two quantities, the binding enthalpy and the binding entropy, it is evident that a more efficient optimization would be accomplished if both quantities were considered and improved simultaneously. Here, an optimization algorithm based upon enthalpic and entropic information generated by Isothermal Titration Calorimetry is presented.

  5. Long Maturity Forward Rates

    DEFF Research Database (Denmark)

    Christiansen, Charlotte

    2001-01-01

    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......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...

  6. Stacking the odds for Golgi cisternal maturation.

    Science.gov (United States)

    Mani, Somya; Thattai, Mukund

    2016-01-01

    What is the minimal set of cell-biological ingredients needed to generate a Golgi apparatus? The compositions of eukaryotic organelles arise through a process of molecular exchange via vesicle traffic. Here we statistically sample tens of thousands of homeostatic vesicle traffic networks generated by realistic molecular rules governing vesicle budding and fusion. Remarkably, the plurality of these networks contain chains of compartments that undergo creation, compositional maturation, and dissipation, coupled by molecular recycling along retrograde vesicles. This motif precisely matches the cisternal maturation model of the Golgi, which was developed to explain many observed aspects of the eukaryotic secretory pathway. In our analysis cisternal maturation is a robust consequence of vesicle traffic homeostasis, independent of the underlying details of molecular interactions or spatial stacking. This architecture may have been exapted rather than selected for its role in the secretion of large cargo. PMID:27542195

  7. Stacking the odds for Golgi cisternal maturation.

    Science.gov (United States)

    Mani, Somya; Thattai, Mukund

    2016-01-01

    What is the minimal set of cell-biological ingredients needed to generate a Golgi apparatus? The compositions of eukaryotic organelles arise through a process of molecular exchange via vesicle traffic. Here we statistically sample tens of thousands of homeostatic vesicle traffic networks generated by realistic molecular rules governing vesicle budding and fusion. Remarkably, the plurality of these networks contain chains of compartments that undergo creation, compositional maturation, and dissipation, coupled by molecular recycling along retrograde vesicles. This motif precisely matches the cisternal maturation model of the Golgi, which was developed to explain many observed aspects of the eukaryotic secretory pathway. In our analysis cisternal maturation is a robust consequence of vesicle traffic homeostasis, independent of the underlying details of molecular interactions or spatial stacking. This architecture may have been exapted rather than selected for its role in the secretion of large cargo.

  8. Affinity of hydroxyapatite by radionuclides parent/child in {sup 188}Re/{sup 188}W generator for radiotherapy; Afinidad de la hidroxiapatita por los radionuclidos padre/hijo en el generador {sup 188}Re/{sup 188}W para radioterapia

    Energy Technology Data Exchange (ETDEWEB)

    Carrera D, A. A. [Universidad Autonoma de Zacatecas, Unidad Academica de Ciencias Quimicas, Campus Universitario Siglo XXI, Ejido La Escondida, Carretera a Guadalajara Km. 6 (Mexico); Badillo A, V. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela 98068, Zacatecas (Mexico); Badillo A, V. E.; Monroy G, F. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)], e-mail: ana_carrera7@hotmail.com

    2009-10-15

    To assess the feasibility of using apatites as matrices of {sup 188}W/{sup 188}Re generator is essential to obtain the distribution coefficients as much of parent radionuclide as child radionuclide in apatite, that is to say to know their affinity for the solid. It was selected the mineral species more representative as adsorbent, the hydroxyapatite Ca{sub 10} (PO{sub 4}){sub 6}(OH){sub 2} it is known for its great capacity of ions retention and by presenting a large affinity for anionic species in their surface. In this paper we use a synthetic hydroxyapatite marketed by Bio-Rad. This paper presents the preliminary results regarding the affinity of hydroxyapatite for the anionic species tungstates (WO{sub 4}{sup 2-}) and perrhenates (ReO{sub 4}{sup -} in EDTA, as background electrolyte expressed as distribution coefficients between two immiscible phases obtained with the help of radioactive tracers {sup 187}W and {sup 188}Re respectively. The retention measures of these ions, traces show that Bio-Gel hydroxyapatite presents moderate values of distribution coefficients for anionic species of W(Vi) in EDTA 0.01 mol/L that are in the range p H 5 to 6.5; the parent radionuclide of generator {sup 188}Re/{sup 188}W is fixed but not enough to consider it a good absorbent. By contrast, the fixation of perrhenate ions is virtually wiped as may be easily removed from a hydroxyapatite column packed with a saline solution. The influence of this saline solution in the removal of perrhenate ions is null practically. (Author)

  9. 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...

  10. On the defining relations of the affine Lie superalgebras and their quantized universal enveloping superalgebras

    CERN Document Server

    Yamane, H

    1996-01-01

    In this paper, we give defining relations of the affine Lie superalgebras an and defining relations of a super-version of the Drinfeld[D]-Jimbo[J] affine quantized universal enveloping algebras. As a result, we can exactly define the affine quantized universal enveloping superalgebras with generators and relations. Moreover we give a Drinfeld's realizations of U_h({\\hat {sl}}(m|n)^{(1)}).

  11. 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...

  12. 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 ...

  13. 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.

  14. 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...

  15. 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...

  16. Recognition: a key retention strategy for the mature nurse.

    Science.gov (United States)

    Bryant-Hampton, Linda; Walton, Ann Marie; Carroll, Tracy; Strickler, Laura

    2010-03-01

    Recognition of staff can be one of the easiest, cost-effective strategies to retain experienced mature nursing staff. The authors discuss the Senior and Generational Excellence initiative that identifies strategies and brings attention to the unique skills and needs of mature professional nurses.

  17. Lectin affinity chromatography of glycolipids

    Energy Technology Data Exchange (ETDEWEB)

    Torres, B.V.; Smith, D.F.

    1987-05-01

    Since glycolipids (GLs) are either insoluble or form mixed micelles in water, lectin affinity chromatography in aqueous systems has not been applied to their separation. They have overcome this problem by using tetrahydrofuran (THF) in the mobile phase during chromatography. Affinity columns prepared with the GalNAc-specific Helix pomatia agglutinin (HPA) and equilibrated in THF specifically bind the (/sup 3/H)oligosaccharide derived from Forssman GL indicating that the immobilized HPA retained its carbohydrate-binding specificity in this solvent. Intact Forssman GL was bound by the HPA-column equilibrated in THF and was specifically eluted with 0.1 mg/ml GalNAc in THF. Purification of the Forssman GL was achieved when a crude lipid extract of sheep erythrocyte membranes was applied to the HPA-column in THF. Non-specifically bound GLs were eluted from the column using a step gradient of aqueous buffer in THF, while the addition of GalNAc was required to elute the specifically bound GLs. Using this procedure the A-active GLs were purified from a crude lipid extract of type A human erythrocytes in a single chromatographic step. The use of solvents that maintain carbohydrate-binding specificity and lipid solubility will permit the application of affinity chromatography on immobilized carbohydrate-binding proteins to intact GLs.

  18. 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)

  19. Comparison of maturity based on steroid and vanadyl porphyrin parameters: A new vanadyl porphyrin maturity parameter for higher maturities

    Science.gov (United States)

    Sundararaman, Padmanabhan; Moldowan, J. Michael

    1993-03-01

    Correlations are demonstrated between steroid maturity parameters and the porphyrin maturity parameter (PMP) which is based on the ratio of specific vanadyl porphyrins C 28E /(C 28E + C 32D) measured by HPLC. Measurements from a global selection of > 100 rock extracts and oils show that PMP parallels changes in the C 29-sterane 20S/(20S + 20R) and tri/(tri + mono) aromatic steroid ratios, and that all three parameters appear to attain their maximum values at similar maturity levels. The triaromatic steroid side chain cracking parameter, TA I/(I + II), reaches approximately 20% of its maximum value when PMP has reached 100%. These results suggest that PMP is effective in the early to peak portion of the oil window. A new parameter, PMP-2, based on changes in the relative concentrations of two peaks in the HPLC fingerprint (vanadyl "etio" porphyrins), appears effective in assessing the maturity of source rocks beyond peak oil generation. In combination with PMP this parameter extends the effective range of vanadyl porphyrins parameters to higher maturities as demonstrated by a suite of oils from the Oriente Basin, Ecuador, South America.

  20. 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

  1. 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

  2. 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).

  3. A Socioanalytic Model of Maturity

    Science.gov (United States)

    Hogan, Robert; Roberts, Brent W.

    2004-01-01

    K0 describes a point of view on maturity that departs from earlier treatments in two ways. First, it rejects the popular assumption from humanistic psychology that maturity is a function of self-actualization and stipulates that maturity is related to certain performance capacities--namely, the ability to form lasting relationships and to achieve…

  4. Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity.

    Science.gov (United States)

    Boder, E T; Midelfort, K S; Wittrup, K D

    2000-09-26

    Single-chain antibody mutants have been evolved in vitro with antigen-binding equilibrium dissociation constant K(d) = 48 fM and slower dissociation kinetics (half-time > 5 days) than those for the streptavidin-biotin complex. These mutants possess the highest monovalent ligand-binding affinity yet reported for an engineered protein by over two orders of magnitude. Optimal kinetic screening of randomly mutagenized libraries of 10(5)-10(7) yeast surface-displayed antibodies enabled a >1,000-fold decrease in the rate of dissociation after four cycles of affinity mutagenesis and screening. The consensus mutations are generally nonconservative by comparison with naturally occurring mouse Fv sequences and with residues that do not contact the fluorescein antigen in the wild-type complex. The existence of these mutants demonstrates that the antibody Fv architecture is not intrinsically responsible for an antigen-binding affinity ceiling during in vivo affinity maturation.

  5. 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.

  6. 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

  7. 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...

  8. 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

  9. hPEPT1 Affinity and Translocation of Selected Gln-Sar and Glu-Sar Dipeptide Derivatives

    DEFF Research Database (Denmark)

    Eriksson, A. H.; Elm, Peter L.; Begtrup, Mikael;

    2005-01-01

    . The esters l-Glu(O-i-Bu)-Sar and l-Glu(OCH2Ada)-Sar and the amides l-Gln(N,N-dimethyl)-Sar and l-Gln(N-piperidinyl)-Sar were synthesized, and affinity to and translocation via hPEPT1 were investigated in mature Caco-2 cell monolayers, grown on permeable supports. Affinity was estimated in a competition assay...

  10. 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...

  11. Graded electron affinity electron source

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, J.L.; Gray, H.F.; Jensen, K.L.; Jung, T.M. [Naval Research Laboratory, Washington, DC 20375 (United States)

    1996-05-01

    We describe a new electron source using electric field and low electron affinity semiconductor materials to bring charge to potential energy levels near the vacuum level while still in the solid. The basic idea involves moving some of the potential barrier from the surface to the bulk, and distributing the barrier over a thin layer below the surface. In so doing, the emission physics is changed fundamentally from a quantum mechanical tunneling process largely controlled by surface properties to a classical transport process largely controlled by the band structure of a wide bandgap semiconductor. The composition of the thin layer below the surface would be graded such that the conduction band minimum changes from an energy close to the substrate Fermi level to an energy significantly closer to the vacuum level. Electrons from the substrate would be drawn into the graded composition layer with an electric field produced by a pointed emitter structure and extraction gate similar to that used in field emitter arrays. Relative to a conventional field emitter array, the new source is expected to require lower extraction fields and exhibit improved emission uniformity, stability, and noise. The {ital I}{endash}{ital V} characteristics are not Fowler{endash}Nordheim and may include a saturation effect at high current densities that could be engineered to improve reliability and uniformity. The group III nitrides can be grown with a continuous range of composition that provides the range of electron affinity needed to produce the proposed electronic structure. {copyright} {ital 1996 American Vacuum Society}

  12. 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

  13. On the Meaning of Affinity Limits in B-Cell Epitope Prediction for Antipeptide Antibody-Mediated Immunity

    Directory of Open Access Journals (Sweden)

    Salvador Eugenio C. Caoili

    2012-01-01

    Full Text Available B-cell epitope prediction aims to aid the design of peptide-based immunogens (e.g., vaccines for eliciting antipeptide antibodies that protect against disease, but such antibodies fail to confer protection and even promote disease if they bind with low affinity. Hence, the Immune Epitope Database (IEDB was searched to obtain published thermodynamic and kinetic data on binding interactions of antipeptide antibodies. The data suggest that the affinity of the antibodies for their immunizing peptides appears to be limited in a manner consistent with previously proposed kinetic constraints on affinity maturation in vivo and that cross-reaction of the antibodies with proteins tends to occur with lower affinity than the corresponding reaction of the antibodies with their immunizing peptides. These observations better inform B-cell epitope prediction to avoid overestimating the affinity for both active and passive immunization; whereas active immunization is subject to limitations of affinity maturation in vivo and of the capacity to accumulate endogenous antibodies, passive immunization may transcend such limitations, possibly with the aid of artificial affinity-selection processes and of protein engineering. Additionally, protein disorder warrants further investigation as a possible supplementary criterion for B-cell epitope prediction, where such disorder obviates thermodynamically unfavorable protein structural adjustments in cross-reactions between antipeptide antibodies and proteins.

  14. 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...

  15. 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...

  16. Ordinary differential equations in affine geometry

    Directory of Open Access Journals (Sweden)

    Salvador Gigena

    1996-05-01

    Full Text Available The method of qualitative analysis is used, as applied to a class of fourth order, nonlinear ordinary differential equations, in order to classify, both locally and globally, two classes of hypersurfaces of decomposable type in affine geometry: those with constant unimodular affine mean curvature L , and those with constant Riemannian scalar curvature R. This allows to provide a large number of new examples of hypersurfaces in affine geometry.

  17. Ordinary differential equations in affine geometry

    OpenAIRE

    Salvador Gigena

    1996-01-01

    The method of qualitative analysis is used, as applied to a class of fourth order, nonlinear ordinary differential equations, in order to classify, both locally and globally, two classes of hypersurfaces of decomposable type in affine geometry: those with constant unimodular affine mean curvature L , and those with constant Riemannian scalar curvature R. This allows to provide a large number of new examples of hypersurfaces in affine geometry.

  18. Affine connections, midpoint formation, and point reflection

    DEFF Research Database (Denmark)

    Kock, Anders

    2011-01-01

    We describe some differential-geometric structures in combinatorial terms: namely affine connections and their torsion and curvature, and we show that torsion free affine connections may equivalently be presented in terms of some simpler combinatorial structure: midpoint formation, and point refl...... reflection (geodesic symmetry). The method employed is that of synthetic differential geometry, which is briefly explained.......We describe some differential-geometric structures in combinatorial terms: namely affine connections and their torsion and curvature, and we show that torsion free affine connections may equivalently be presented in terms of some simpler combinatorial structure: midpoint formation, and point...

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. Improving Binding Affinity and Selectivity of Computationally Designed Ligand-Binding Proteins Using Experiments.

    Science.gov (United States)

    Tinberg, Christine E; Khare, Sagar D

    2016-01-01

    The ability to de novo design proteins that can bind small molecules has wide implications for synthetic biology and medicine. Combining computational protein design with the high-throughput screening of mutagenic libraries of computationally designed proteins is emerging as a general approach for creating binding proteins with programmable binding modes, affinities, and selectivities. The computational step enables the creation of a binding site in a protein that otherwise does not (measurably) bind the intended ligand, and targeted mutagenic screening allows for validation and refinement of the computational model as well as provides orders-of-magnitude increases in the binding affinity. Deep sequencing of mutagenic libraries can provide insights into the mutagenic binding landscape and enable further affinity improvements. Moreover, in such a combined computational-experimental approach where the binding mode is preprogrammed and iteratively refined, selectivity can be achieved (and modulated) by the placement of specified amino acid side chain groups around the ligand in defined orientations. Here, we describe the experimental aspects of a combined computational-experimental approach for designing-using the software suite Rosetta-proteins that bind a small molecule of choice and engineering, using fluorescence-activated cell sorting and high-throughput yeast surface display, high affinity and ligand selectivity. We illustrated the utility of this approach by performing the design of a selective digoxigenin (DIG)-binding protein that, after affinity maturation, binds DIG with picomolar affinity and high selectivity over structurally related steroids. PMID:27094290

  4. 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…

  5. Antibody VH and VL recombination using phage and ribosome display technologies reveals distinct structural routes to affinity improvements with VH-VL interface residues providing important structural diversity.

    Science.gov (United States)

    Groves, Maria A T; Amanuel, Lily; Campbell, Jamie I; Rees, D Gareth; Sridharan, Sudharsan; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

    2014-01-01

    In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe the isolation of a parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. KENB061 was affinity matured using phage display and targeted mutagenesis of VH and VL CDR3 using NNS randomization. Affinity matured VHCDR3 and VLCDR3 library blocks were recombined and selected using phage and ribosome display protocol. A direct comparison of the phage and ribosome display antibodies generated was made to determine their functional characteristics.In our analyses, we observed distinct differences in the pattern of beneficial mutations in antibodies derived from phage and ribosome display selections, and discovered the lead antibody Jedi067 had a ~3700-fold improvement in KD over the parent KENB061. We constructed a homology model of the Fv region of Jedi067 to map the specific positions where mutations occurred in the CDR3 loops. For VL CDR3, positions 94 to 97 carry greater diversity in the ribosome display variants compared with the phage display. The positions 95a, 95b and 96 of VLCDR3 form part of the interface with VH in this model. The model shows that positions 96, 98, 100e, 100f, 100 g, 100h, 100i and 101 of the VHCDR3 include residues at the VH and VL interface. Importantly, Leu96 and Tyr98 are conserved at the interface positions in both phage and ribosome display indicating their importance in maintaining the VH-VL interface. For antibodies derived from ribosome display, there is significant diversity at residues 100a to 100f of the VH CDR3 compared with phage display. A unique deletion of isoleucine at position 102 of the lead candidate, Jedi067, also occurs in the VHCDR3.As anticipated, recombining the mutations via ribosome display led to a greater structural diversity, particularly in the heavy chain CDR3, which in turn

  6. Affine processes on positive semidefinite matrices

    CERN Document Server

    Cuchiero, Christa; Mayerhofer, Eberhard; Teichmann, Josef

    2009-01-01

    This paper provides the mathematical foundation for stochastically continuous affine processes on the cone of positive semidefinite symmetric matrices. These matrix-valued affine processes have arisen from a large and growing range of useful applications in finance, including multi-asset option pricing with stochastic volatility and correlation structures, and fixed-income models with stochastically correlated risk factors and default intensities.

  7. 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.

  8. Global affine differential geometry of hypersurfaces

    CERN Document Server

    Li, An-Min; Zhao, Guosong; Hu, Zejun

    2015-01-01

    This book draws a colorful and widespread picture of global affine hypersurface theory up to the most recent state. Moreover, the recent development revealed that affine differential geometry- as differential geometry in general- has an exciting intersection area with other fields of interest, like partial differential equations, global analysis, convex geometry and Riemann surfaces.

  9. 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.

  10. 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.

  11. 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.

  12. Phosphopeptide enrichment by immobilized metal affinity chromatography

    DEFF Research Database (Denmark)

    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...

  13. 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.

  14. GHB receptor targets in the CNS: Focus on high-affinity binding sites

    DEFF Research Database (Denmark)

    Bay, Tina; Eghorn, Laura Friis; Klein, Anders Bue;

    2014-01-01

    γ-Hydroxybutyric acid (GHB) is an endogenous compound in the mammalian brain with both low- and high-affinity receptor targets. GHB is used clinically in the treatment of symptoms of narcolepsy and alcoholism, but also illicitly abused as the recreational drug Fantasy. Major pharmacological effects...... of exogenous GHB are mediated by GABA subtype B (GABAB) receptors that bind GHB with low affinity. The existence of GHB high-affinity binding sites has been known for more than three decades, but the uncovering of their molecular identity has only recently begun. This has been prompted by the generation...... of molecular tools to selectively study high-affinity sites. These include both genetically modified GABAB knock-out mice and engineered selective GHB ligands. Recently, certain GABA subtype A (GABAA) receptor subtypes emerged as high-affinity GHB binding sites and potential physiological mediators of GHB...

  15. Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens

    DEFF Research Database (Denmark)

    Andersen, P S; Geisler, C; Buus, S;

    2001-01-01

    (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency......Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3...... correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength....

  16. 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.

  17. Reflectable bases for affine reflection systems

    CERN Document Server

    Azam, Saeid; Yousofzadeh, Malihe

    2011-01-01

    The notion of a "root base" together with its geometry plays a crucial role in the theory of finite and affine Lie theory. However, it is known that such a notion does not exist for the recent generalizations of finite and affine root systems such as extended affine root systems and affine reflection systems. As an alternative, we introduce the notion of a "reflectable base", a minimal subset $\\Pi$ of roots such that the non-isotropic part of the root system can be recovered by reflecting roots of $\\Pi$ relative to the hyperplanes determined by $\\Pi$. We give a full characterization of reflectable bases for tame irreducible affine reflection systems of reduced types, excluding types $E_{6,7,8}$. As a byproduct of our results, we show that if the root system under consideration is locally finite then any reflectable base is an integral base.

  18. Fatty acid and drug binding to a low-affinity component of human serum albumin, purified by affinity chromatography

    DEFF Research Database (Denmark)

    Vorum, H; Pedersen, A O; Honoré, B

    1992-01-01

    of two albumin components about 40% of the albumin having high affinity and about 60% having low affinity. By affinity chromatography we succeeded in purifying the low-affinity component from the mixture. The high-affinity component, however, could not be isolated. We further analyzed the fatty acid...... and drug binding abilities of the low-affinity component. The fatty acids decanoate, laurate, myristate and palmitate were bound with higher affinity to the mixture than to the low-affinity component. Diazepam was bound with nearly the same affinity to the low-affinity component as to the albumin mixture...

  19. TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells.

    Science.gov (United States)

    Takada, Kensuke; Van Laethem, Francois; Xing, Yan; Akane, Kazuyuki; Suzuki, Haruhiko; Murata, Shigeo; Tanaka, Keiji; Jameson, Stephen C; Singer, Alfred; Takahama, Yousuke

    2015-10-01

    In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8(+) T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8(+) T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8(+) T cells in the periphery.

  20. 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.

  1. 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.

  2. 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...

  3. Non-Zenoness of piecewise affine dynamical systems and affine complementarity systems with inputs

    Institute of Scientific and Technical Information of China (English)

    Le Quang THUAN

    2014-01-01

    In the context of continuous piecewise affine dynamical systems and affine complementarity systems with inputs, we study the existence of Zeno behavior, i.e., infinite number of mode transitions in a finite-length time interval, in this paper. The main result reveals that continuous piecewise affine dynamical systems with piecewise real-analytic inputs do not exhibit Zeno behavior. Applied the achieved result to affine complementarity systems with inputs, we also obtained a similar conclusion. A direct benefit of the main result is that one can apply smooth ordinary differential equations theory in a local manner for the analysis of continuous piecewise affine dynamical systems with inputs.

  4. Determinism and stochasticity during maturation of the zebrafish antibody repertoire

    Science.gov (United States)

    Jiang, Ning; Weinstein, Joshua A.; Penland, Lolita; White, Richard A.; Fisher, Daniel S.; Quake, Stephen R.

    2011-01-01

    It is thought that the adaptive immune system of immature organisms follows a more deterministic program of antibody creation than is found in adults. We used high-throughput sequencing to characterize the diversifying antibody repertoire in zebrafish over five developmental time points. We found that the immune system begins in a highly stereotyped state with preferential use of a small number of V (variable) D (diverse) J (joining) gene segment combinations, but that this stereotypy decreases dramatically as the zebrafish mature, with many of the top VDJ combinations observed in 2-wk-old zebrafish virtually disappearing by 1 mo. However, we discovered that, in the primary repertoire, there are strong correlations in VDJ use that increase with zebrafish maturity, suggesting that VDJ recombination involves a level of deterministic programming that is unexpected. This stereotypy is masked by the complex diversification processes of antibody maturation; the variation and lack of correlation in full repertoires between individuals appears to be derived from randomness in clonal expansion during the affinity maturation process. These data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to better understand how the adaptive immune system achieves diversity. PMID:21393572

  5. 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

  6. 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...

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Product Maturation Guide - A Digital Simulation Outcome

    DEFF Research Database (Denmark)

    Boorla, Srinivasa Murthy; Howard, Thomas J.

    2016-01-01

    . Tolerance analysis tools, those optimizing the individual part tolerances at the time of design can generate a product maturation guide that eliminates many problem solving procedures and saves time on root cause analysis. Assume a first product built on a new assembly line was found to need improvements...... range, it has to consider one fixed value measured from initial parts. By adding information about process characteristics, like speed, cost, etc. to all the dimensions, the system can directly guide the manufacturing team, on which parameter to modify, which direction and how much. At the same time...

  13. 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.

  14. 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

  15. 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

  16. 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...

  17. 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.

  18. 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...

  19. 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...

  20. 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...

  1. 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)

  2. 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.

  3. The connection between metal ion affinity and ligand affinity in integrin I domains

    DEFF Research Database (Denmark)

    Vorup-Jensen, Thomas; Waldron, TT; Astrof, N;

    2007-01-01

    Integrins are cell-surface heterodimeric proteins that mediate cell-cell, cell-matrix, and cell-pathogen interactions. Half of the known integrin alpha subunits contain inserted domains (I domains) that coordinate ligand through a metal ion. Although the importance of conformational changes within...... isolated I domains in regulating ligand binding has been reported, the relationship between metal ion binding affinity and ligand binding affinity has not been elucidated. Metal and ligand binding by several I domain mutants that are stabilized in different conformations are investigated using isothermal...... titration calorimetry and surface plasmon resonance studies. This work suggests an inverse relationship between metal ion affinity and ligand binding affinity (i.e. constructs with a high affinity for ligand exhibit a low affinity for metal). This trend is discussed in the context of structural studies...

  4. 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...

  5. 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

  6. Con A affinity glycoproteomics of normal human liver tissue

    Institute of Scientific and Technical Information of China (English)

    SUN QiangLing; LU HaoJie; LIU YinKun; LU WenJing; CHENG Gang; ZHOU HaiJun; ZHOU XinWen; WEI LiMing; DAI Zhi; GUO Kun

    2007-01-01

    In order to establish the novel high throughput, high efficiency and Iow cost technological platform for the research of N-glycoproteomics, to resolve the significance of characteristic expression profile of glycoprotein and to find the proteins with biological functional importance, the glycoproteins with high-mannose core and the two antennary types were purified and enriched by the Con A affinity chromatography. Con A affinity protein expression profiles of normal human liver tissue were generated by using SDS-PAGE, two-dimensional electrophoresis (2-DE) followed by fast fluorescence staining based on multiplexed proteomics (MP) technology. 301 visible protein spots on the gel were detected and 85 of glycoproteins were further successfully identified via peptide mass fingerprinting (PMF) by a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS/MS) and annotated to IPI databases. Identified glycoproteins definitely take part in the regulation of cell cycle and metabolic processes. The glycosylation sites were predicted with NetNGlyc 1.0 and NetOGlyc 3.1 software, meanwhile they were classified according to the geneontology methods. The construction of Con A affinity glycoprotein database of normal human liver tissue would contribute to the subsequent research.

  7. Effective Optimization of Antibody Affinity by Phage Display Integrated with High-Throughput DNA Synthesis and Sequencing Technologies.

    Directory of Open Access Journals (Sweden)

    Dongmei Hu

    Full Text Available Phage display technology has been widely used for antibody affinity maturation for decades. The limited library sequence diversity together with excessive redundancy and labour-consuming procedure for candidate identification are two major obstacles to widespread adoption of this technology. We hereby describe a novel library generation and screening approach to address the problems. The approach started with the targeted diversification of multiple complementarity determining regions (CDRs of a humanized anti-ErbB2 antibody, HuA21, with a small perturbation mutagenesis strategy. A combination of three degenerate codons, NWG, NWC, and NSG, were chosen for amino acid saturation mutagenesis without introducing cysteine and stop residues. In total, 7,749 degenerate oligonucleotides were synthesized on two microchips and released to construct five single-chain antibody fragment (scFv gene libraries with 4 x 10(6 DNA sequences. Deep sequencing of the unselected and selected phage libraries using the Illumina platform allowed for an in-depth evaluation of the enrichment landscapes in CDR sequences and amino acid substitutions. Potent candidates were identified according to their high frequencies using NGS analysis, by-passing the need for the primary screening of target-binding clones. Furthermore, a subsequent library by recombination of the 10 most abundant variants from four CDRs was constructed and screened, and a mutant with 158-fold increased affinity (Kd = 25.5 pM was obtained. These results suggest the potential application of the developed methodology for optimizing the binding properties of other antibodies and biomolecules.

  8. 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

  9. Classification of neocortical interneurons using affinity propagation

    Science.gov (United States)

    Santana, Roberto; McGarry, Laura M.; Bielza, Concha; Larrañaga, Pedro; Yuste, Rafael

    2013-01-01

    In spite of over a century of research on cortical circuits, it is still unknown how many classes of cortical neurons exist. In fact, neuronal classification is a difficult problem because it is unclear how to designate a neuronal cell class and what are the best characteristics to define them. Recently, unsupervised classifications using cluster analysis based on morphological, physiological, or molecular characteristics, have provided quantitative and unbiased identification of distinct neuronal subtypes, when applied to selected datasets. However, better and more robust classification methods are needed for increasingly complex and larger datasets. Here, 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. Affinity propagation outperformed Ward's method, a current standard clustering approach, in classifying the neurons into 4 subtypes. Affinity propagation could therefore be used in future studies to validly classify neurons, as a first step to help reverse engineer neural circuits. PMID:24348339

  10. 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.

  11. 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.

  12. Public Sector IS Maturity Models

    DEFF Research Database (Denmark)

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

    2011-01-01

    citizenpublic interaction, such as in public education. In this paper we use a revised version of the Public Sector Process Rebuilding (PPR) maturity model for mapping 200 websites of public primary schools in Denmark. Findings reveal a much less favorable picture of the digitization of the Danish public sector...

  13. Rhetorical Maturity: Definition and Development.

    Science.gov (United States)

    Miller, Susan

    Lawrence Kohlberg's stages of moral development, when applied to theories of teaching composition, support any method or material that refers to the age and prior experience of the writer and the newness of the task the writer is attempting. Rhetorical development and maturation in the ability to write and argue persuasively are partly conceptual…

  14. Stepparents' Affinity-Seeking and Affinity-Maintaining Strategies with Stepchildren.

    Science.gov (United States)

    Ganong, Lawrence; Coleman, Marilyn; Fine, Mark; Martin, Patricia

    1999-01-01

    Examines the strategies that stepparents use to develop and maintain affinity with stepchildren and the effects that these strategies have on the development of stepparent-stepchildren relationships. Thirty-one affinity-seeking strategies are identified. Results show that dyadic activities worked best, but it is important that stepchildren…

  15. 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.

  16. Affinity chromatography of bacterial lactate dehydrogenases.

    Science.gov (United States)

    Kelly, N; Delaney, M; O'Carra, P

    1978-06-01

    The affinity system used was the immobilized oxamate derivative previously used to purify mammalian lactate dehydrogenases. The bacterial dehydrogenases specific for the L-stereoisomer of lactate behaved in the same way as the mammalian enzymes, binding strongly in the presence of NADH. The D-lactate-specific enzymes, however, did not show any biospecific affinity for this gel. The L-specific enzymes could be purified to homogeneity in one affinity-chromatographic step. The D-specific enzymes could be efficiently separated from the L-specific ones and could then be further purified on an immobilized NAD derivative. The mechanism of activation of the lactate dehydrogenase from Streptococcus faecalis by fructose 1,6-bisphosphate was investigated by using the immobilized oxamate gel. PMID:666726

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. Affine Invariant Character Recognition by Progressive Removing

    Science.gov (United States)

    Iwamura, Masakazu; Horimatsu, Akira; Niwa, Ryo; Kise, Koichi; Uchida, Seiichi; Omachi, Shinichiro

    Recognizing characters in scene images suffering from perspective distortion is a challenge. Although there are some methods to overcome this difficulty, they are time-consuming. In this paper, we propose a set of affine invariant features and a new recognition scheme called “progressive removing” that can help reduce the processing time. Progressive removing gradually removes less feasible categories and skew angles by using multiple classifiers. We observed that progressive removing and the use of the affine invariant features reduced the processing time by about 60% in comparison to a trivial one without decreasing the recognition rate.

  2. Adsorption affinity of anions on metal oxyhydroxides

    Science.gov (United States)

    Pechenyuk, S. I.; Semushina, Yu. P.; Kuz'mich, L. F.

    2013-03-01

    The dependences of anion (phosphate, carbonate, sulfate, chromate, oxalate, tartrate, and citrate) adsorption affinity anions from geometric characteristics, acid-base properties, and complex forming ability are generalized. It is shown that adsorption depends on the nature of both the anions and the ionic medium and adsorbent. It is established that anions are generally grouped into the following series of adsorption affinity reduction: PO{4/3-}, CO{3/2-} > C2O{4/2-}, C(OH)(CH2)2(COO){3/3-}, (CHOH)2(COO){2/2-} > CrO{4/2-} ≫ SO{4/2-}.

  3. 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

  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. 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 :

  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 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...

  8. 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.

  9. 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)

  10. 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...

  11. 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

  12. Fan Affinity Laws from a Collision Model

    Science.gov (United States)

    Bhattacharjee, Shayak

    2012-01-01

    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…

  13. 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.

  14. 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...

  15. 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

  16. A Disposable Sensor For Assessing Artocarpus heterophyllus L. (Jackfruit Maturity

    Directory of Open Access Journals (Sweden)

    Chang Chew Cheen

    2003-12-01

    Full Text Available The purpose of this work was an attempt to monitor the ripeness process and to investigate the different maturity stages of jackfruit by chemometric treatment of the data obtained from the disposable sensor. Response of the sensor strip fabricated using screenprinting technology was analyzed using Principal Component Analysis (PCA and the classification model constructed by means of Canonical Discriminant Analysis (CDA enable unknown maturity stages of jackfruit to be identified. Results generated from the combination of the two classification principles show the capability and the performance of the sensor strip towards jackfruit analysis.

  17. 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.

  18. GHB receptor targets in the CNS: focus on high-affinity binding sites.

    Science.gov (United States)

    Bay, Tina; Eghorn, Laura F; Klein, Anders B; Wellendorph, Petrine

    2014-01-15

    γ-Hydroxybutyric acid (GHB) is an endogenous compound in the mammalian brain with both low- and high-affinity receptor targets. GHB is used clinically in the treatment of symptoms of narcolepsy and alcoholism, but also illicitly abused as the recreational drug Fantasy. Major pharmacological effects of exogenous GHB are mediated by GABA subtype B (GABAB) receptors that bind GHB with low affinity. The existence of GHB high-affinity binding sites has been known for more than three decades, but the uncovering of their molecular identity has only recently begun. This has been prompted by the generation of molecular tools to selectively study high-affinity sites. These include both genetically modified GABAB knock-out mice and engineered selective GHB ligands. Recently, certain GABA subtype A (GABAA) receptor subtypes emerged as high-affinity GHB binding sites and potential physiological mediators of GHB effects. In this research update, a description of the various reported receptors for GHB is provided, including GABAB receptors, certain GABAA receptor subtypes and other reported GHB receptors. The main focus will thus be on the high-affinity binding targets for GHB and their potential functional roles in the mammalian brain.

  19. 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.

  20. Characterization of Green River Kerogen upon Induced Maturation

    Science.gov (United States)

    Alsinan, S.; Vanorio, T.

    2015-12-01

    The aim of this research is to investigate the effects of organic maturity on the elastic properties of kerogen, and then model its effect on the rock elastic responses. To fulfill this objective, we present a workflow that combines nano-scale Secondary Ion Mass Spectrometry (nanoSIMS), nanoindentation, SEM, ex situ maturation experiments, RockEval analysis and Self-Consistent modeling (SC). First, we used SEM and nanoSIMS to identify the organic rich-kerogen bodies. NanoSIMS provided maps of the secondary ion intensity distribution of H-, C- and O- which show a uniform distribution of these ions within the immature kerogen body. The measured H- /C- and O-/C- ionic intensity ratios range between 1.40 ±0.86 -1.69 ±0.61 and 0.77 ±0.72 - 1.04 ±0.44 respectively. Next, we used the nanoindentation technique to measure the elastic properties of an immature Green River kerogen, which had an average bulk modulus (K) of 3.11 ± 0.23 GPa. Then, we induced maturation using a High Temperature-High Pressure vessel that mimics reservoir conditions. Ex situ maturation resulted in a strong hydrocarbon smell, oil staining, and the expulsion of an oil-like viscous fluid. Geochemical analysis confirmed that the sample had successfully matured to the oil window. SEM time-lapse images show porosity (ϕ) development within the kerogen and surrounding matrix as a result of maturation. Once maturation was complete, we re-measured the elastic properties of the kerogen in the sample using the same nanoindentation technique. The average value of K of the mature kerogen (oil window) was 3.65 ±0.67 GPa. Therefore, we conclude that changes in the elastic properties of solid kerogen in the oil window are negligible. However, ϕ development within the kerogen, the shape of kerogen and its pores, and the presence of fluid can affect the composite rock stiffness. Therefore, we used SC modeling to investigate the effect of ϕ development within the kerogen associated with ex situ maturation, on

  1. 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...

  2. 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...

  3. 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......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 native and abnormally folded beta2-microglobulin. We find that native beta2-microglobulin has an intermediate affinity for Congo red at pH 7.3 and that binding involves electrostatic interactions. The conformational variant of beta2-microglobulin that appears in acetonitrile solutions binds Congo red...... more strongly. Affinity CE using Congo red as a buffer additive is a new, simple, fast, and quantitative micromethod for the characterization of soluble conformational intermediates of amyloidogenic proteins....

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Local structure of self-affine sets

    CERN Document Server

    Bandt, Christoph

    2011-01-01

    The structure of a self-similar set with open set condition does not change under magnification. For self-affine sets the situation is completely different. We consider planar self-affine Cantor sets E of the type studied by Bedford, McMullen, Gatzouras and Lalley, for which the projection onto the horizontal axis is an interval. We show that within small square neighborhoods of almost each point x in E, with respect to many product measures on address space, E is well approximated by product sets of an interval and a Cantor set. Even though E is totally disconnected, the limit sets have the product structure with interval fibres, reminiscent to the view of attractors of chaotic differentiable dynamical systems.

  10. Recent Results Regarding Affine Quantum Gravity

    CERN Document Server

    Klauder, John R

    2012-01-01

    Recent progress in the quantization of nonrenormalizable scalar fields has found that a suitable non-classical modification of the ground state wave function leads to a result that eliminates term-by-term divergences that arise in a conventional perturbation analysis. After a brief review of both the scalar field story and the affine quantum gravity program, examination of the procedures used in the latter surprisingly shows an analogous formulation which already implies that affine quantum gravity is not plagued by divergences that arise in a standard perturbation study. Additionally, guided by the projection operator method to deal with quantum constraints, trial reproducing kernels are introduced that satisfy the diffeomorphism constraints. Furthermore, it is argued that the trial reproducing kernels for the diffeomorphism constraints may also satisfy the Hamiltonian constraint as well.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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...... 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...... 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...

  20. Experimental investigation of streamer affinity for dielectric surfaces

    NARCIS (Netherlands)

    Trienekens, D.J.M.; Nijdam, S.; Akkermans, G.; Plompen, I.; Christen, T.; Ebert, U.

    2015-01-01

    We have experimentally investigated the affinity of streamers for dielectric surfaces using stroboscopic imaging and stereo photography. Affinity of streamers for dielectric surfaces was found to depend on a wide set of parameters, including pressure, voltage, dielectric material and di

  1. 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.

  2. Sexual maturation in kokanee Oncorhynchus nerka

    Science.gov (United States)

    Patterson, S.D.; Scarnecchia, D.L.; Congleton, J.L.

    2008-01-01

    We used observational and experimental approaches to obtain information on factors affecting the timing of maturation of kokanee Oncorhynchus nerka, a semelparous, landlocked salmon. Gonadal staging criteria were developed and applied to three kokanee populations in Idaho lakes and reservoirs. Testes were classified into three stages: immature (stage one, S1), maturing (S2), and mature (S3). Ovaries were classified into eight stages: immature (S1-S3), transitional (stage S4), maturing (S5-S7), and mature (S8). Males entered the maturing stage (S2) in February through April of the spawning year. Females entered maturing stage (S5) as early as July of the year before the spawning year, and as late as March of the spawning year. Three hatchery experiments demonstrated that attainment of a larger body size 10 to 16 months before spawning increased the likelihood of initiation of maturation in both sexes. No gonads in a state of regression were observed. A gonadosomatic index above 0.1 by early July was a good indicator of a maturing male, and a gonadosomatic index above 1.0 by early July was a good indicator of a maturing female. Instantaneous growth rates were not good predictors of maturation, but attaining a size threshold of 18 to 19 cm in the fall was a good predictor of maturation the following year. This improved knowledge of kokanee maturation will permit more effectively management of the species for age, growth and size at maturity as well as for contributions to fisheries. ?? 2008 by the Northwest Scientific Association. All rights reserved.

  3. 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 ...

  4. Low-mature gases and their resource potentiality

    Institute of Scientific and Technical Information of China (English)

    XU Yongchang; WANG Xiaofeng; SHI Baoguang

    2009-01-01

    In the 80's of last century, based on the advances in natural gas exploration practice, the concepts of bio-thermocatalytic transitional-zone gas and early thermogenetic gas were proposed, and the lower limit Ro values for the formation and accumulation of thermogenetic natural gases of industrial importance have been extended to 0.3%-0.4%. In accordance with the two-stage model established on the basis of carbon isotope fractionation involved in the formation of coal-type natural gases, the upper limit Ro values of lowly evolved natural gases should be set at 0.8%-1.0%. This is the concept of low-mature gas which is commonly accepted at the present time. The Urengoy super-large gas field in western Siberian Basin is a typical example of low-mature gas field, where low-mature gas reserves account for 20% of the globally proven natural gas reserves, and this fully indicates the importance of this kind of resources. The proven reserves of natural gases in the Turpan-Hami Basin of China are approximate to 1000×108 m3, and the thermal evolution indices of source rocks are Ro=0.4%-0.8%. The δ13C1 values of methane are mainly within the range of -44‰- -39‰ (corresponding to Ro=0.6%-0.8%), and those of ethane are mainly within the range of -29‰- -26‰, indicating that these natural gases should be designated to the coal-type low-mature gases. The light hydrocarbon evolution indices of natural gases also provide strong evidence suggesting that they are the coal-type low-mature gases. If so, low-mature gas in the Turpan-Hami Basin has been accumulated to such an extent as to be equivalent to the total reserves of three large-sized gas fields, and their existence is of great significance in the study and exploration of China's low-mature gases. If it is evidenced that the source rocks of low-mature gases are related mainly to coal measures, China's abundant lowly evolved coal series resources will provide a huge resource potentiality for the generation of low-mature

  5. Fractal Homeomorphism for Bi-affine Iterated Function Systems

    CERN Document Server

    Barnsley, Michael

    2011-01-01

    The paper concerns fractal homeomorphism between the attractors of two bi-affine iterated function systems. After a general discussion of bi-affine functions, conditions are provided under which a bi-affine iterated function system is contractive, thus guaranteeing an attractor. After a general discussion of fractal homeomorphism, fractal homeomorphisms are constructed for a specific type of bi-affine iterated function system.

  6. 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.)

  7. Type II chiral affine Lie algebras and string actions in doubled space

    CERN Document Server

    Hatsuda, Machiko; Siegel, Warren

    2015-01-01

    We present affine Lie algebras generated by the supercovariant derivatives and the supersymmetry generators for the left and right moving modes in the doubled space. Chirality is manifest in our doubled space as well as the T-duality symmetry. We present gauge invariant bosonic and superstring actions preserving the two-dimensional diffeomorphism invariance and the kappa-symmetry where doubled spacetime coordinates are chiral fields. The doubled space becomes the usual space by dimensional reduction constraints.

  8. Petrographic maturity parameters of a Devonian shale maturation series, Appalachian Basin, USA. ICCP Thermal Indices Working Group interlaboratory exercise

    Science.gov (United States)

    Araujo, Carla Viviane; Borrego, Angeles G.; Cardott, Brian; das Chagas, Renata Brenand A.; Flores, Deolinda; Goncalves, Paula; Hackley, Paul C.; Hower, James C.; Kern, Marcio Luciano; Kus, Jolanta; Mastalerz, Maria; Filho, João Graciano Mendonça; de Oliveira Mendonça, Joalice; Rego Menezes, Taissa; Newman, Jane; Suarez-Ruiz, Isabel; Sobrinho da Silva, Frederico; Viegas de Souza, Igor

    2014-01-01

    max beyond 0.65% vitrinite reflectance was also observed in studies of Devonian shale in other basins, suggesting that the accepted correlation for these two petrographic thermal maturity parameters needs to be re-evaluated.A good linear correlation between λmax and Tmax for this maturation series was observed and λmax 600 nm corresponds to Tmax of 440 °C. Nevertheless if a larger set of Devonian samples is included, the correlation is polynomial with a jump in λmax ranging from 540 to 570 nm. Up to 440 °C of Tmax, the λmax, mostly, reaches up to 500 nm; beyond a Tmax of 440 °C, λmax is in the range of 580–600 nm. This relationship places the “red shift” when the onset of the oil window is reached at Tmax of 440 °C. Moreover, the correlation between HI and λmax (r2 = 0.70) shows a striking inflection and decrease in HI above a λmax of 600 nm, coincident with the approximate onset of hydrocarbon generation in these rocks.

  9. 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 ...

  10. 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...

  11. 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

  12. 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...

  13. 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 $x^{3}-(|p|-1)x^{2}-(|q|-|p|)x-|q|$.

  14. 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.

  15. 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.

  16. 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...

  17. 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

  18. SELMAP - SELEX affinity landscape MAPping of transcription factor binding sites using integrated microfluidics

    Science.gov (United States)

    Chen, Dana; Orenstein, Yaron; Golodnitsky, Rada; Pellach, Michal; Avrahami, Dorit; Wachtel, Chaim; Ovadia-Shochat, Avital; Shir-Shapira, Hila; Kedmi, Adi; Juven-Gershon, Tamar; Shamir, Ron; Gerber, Doron

    2016-01-01

    Transcription factors (TFs) alter gene expression in response to changes in the environment through sequence-specific interactions with the DNA. These interactions are best portrayed as a landscape of TF binding affinities. Current methods to study sequence-specific binding preferences suffer from limited dynamic range, sequence bias, lack of specificity and limited throughput. We have developed a microfluidic-based device for SELEX Affinity Landscape MAPping (SELMAP) of TF binding, which allows high-throughput measurement of 16 proteins in parallel. We used it to measure the relative affinities of Pho4, AtERF2 and Btd full-length proteins to millions of different DNA binding sites, and detected both high and low-affinity interactions in equilibrium conditions, generating a comprehensive landscape of the relative TF affinities to all possible DNA 6-mers, and even DNA10-mers with increased sequencing depth. Low quantities of both the TFs and DNA oligomers were sufficient for obtaining high-quality results, significantly reducing experimental costs. SELMAP allows in-depth screening of hundreds of TFs, and provides a means for better understanding of the regulatory processes that govern gene expression. PMID:27628341

  19. 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.

  20. Analysis of affinely equivalent Boolean functions

    Institute of Scientific and Technical Information of China (English)

    MENG QingShu; ZHANG HuanGuo; YANG Min; WANG ZhangYi

    2007-01-01

    By some basic transforms and invariant theory, we give two results: 1) an algorithm,which can be used to judge if two Boolean functions are affinely equivalent and to obtain the equivalence relationship if they are equivalent. This is useful in studying Boolean functions and in engineering. For example, we classify all 8-variable homogeneous bent functions of degree 3 into two classes; 2) Reed-Muller codes R(4,6)/R(1,6), R(3,7)/R(1,7) are classified efficiently.

  1. 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.

  2. Latest European coelacanth shows Gondwanan affinities.

    Science.gov (United States)

    Cavin, Lionel; Forey, Peter L; Buffetaut, Eric; Tong, Haiyan

    2005-06-22

    The last European fossil occurrence of a coelacanth is from the Mid-Cretaceous of the English Chalk (Turonian, 90 million years ago). Here, we report the discovery of a coelacanth from Late Cretaceous non-marine rocks in southern France. It consists of a left angular bone showing structures that imply close phylogenetic affinities with some extinct Mawsoniidae. The closest relatives are otherwise known from Cretaceous continental deposits of southern continents and suggest that the dispersal of freshwater organisms from Africa to Europe occurred in the Late Cretaceous.

  3. Affine Coherent States in Quantum Cosmology

    CERN Document Server

    Malkiewicz, Przemyslaw

    2015-01-01

    A brief summary of the application of coherent states in the examination of quantum dynamics of cosmological models is given. We discuss quantization maps, phase space probability distributions and semiclassical phase spaces. The implementation of coherent states based on the affine group resolves the hardest singularities, renders self-adjoint Hamiltonians without boundary conditions and provides a completely consistent semi-classical description of the involved quantum dynamics. We consider three examples: the closed Friedmann model, the anisotropic Bianchi Type I model and the deep quantum domain of the Bianchi Type IX model.

  4. Measuring an antibody affinity distribution molecule by molecule

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Werner, James H [Los Alamos National Laboratory; Temirov, Jamshid [INVITROGEN

    2008-01-01

    Single molecule fluorescence mIcroscopy was used to observe the binding and unbinding of hapten decorated quantum dots with individual surface immobilized antibodies. The fluorescence time history from an individual antibody site can be used to calculate its binding affinity. While quantum dot blinking occurs during these measurements, we describe a simple empirical method to correct the apparent/observed affinity to account for the blinking contribution. The combination of many single molecule affinity measurements from different antibodies yields not only the average affinity, it directly measures the full shape and character of the surface affinity distribution function.

  5. 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

  6. 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.

  7. 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

  8. 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)

  9. 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.

  10. Seeking process maturity with DSDM atern

    Directory of Open Access Journals (Sweden)

    Stasys Peldžius

    2013-09-01

    Full Text Available It is important for an organization to know what capability/maturity of the process a chosen methodology could ensure. This paper is focused on DSDM Atern process maturity by CMMI. The goal is to assess DSDM Atern by CMMI-DEV version 1.3 and propose the improvements to reach CMMI maturity level 3. A capability profile ensured by DSDM Atern has been obtained. The appraisal results showed that DSDM Atern ensures CMMI maturity level 2. Constraints and problematic areas of DSDM Atern methodology were discovered. In order to reach CMMI level 3 some recommendations for DSDM Atern additions were developed.

  11. 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.)

  12. 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

  13. Affine Mirkovi\\'c-Vilonen polytopes

    CERN Document Server

    Baumann, Pierre; Tingley, Peter

    2011-01-01

    Each integrable lowest weight representation of a symmetrizable Kac-Moody Lie algebra g has a crystal in the sense of Kashiwara, which describes its combinatorial properties. For a given g, there is a limit crystal, usually denoted by B(-\\infty), which contains all the other crystals. When g is finite dimensional, a convex polytope, called the Mirkovi\\'c-Vilonen polytope, can be associated to each element in B(-\\infty). This polytope sits in the dual space of a Cartan subalgebra of g, and its edges are parallel to the roots of g. In this paper, we generalize this construction to the case where g is a symmetric affine Kac-Moody algebra. The datum of the polytope must however be complemented by partitions attached to the edges parallel to the imaginary root \\delta. We prove that these decorated polytopes are characterized by conditions on their normal fans and on their 2-faces. In addition, we discuss how our polytopes provide an analog of the notion of Lusztig datum for affine Kac-Moody algebras. Our main tool...

  14. Affine conformal vectors in space-time

    Science.gov (United States)

    Coley, A. A.; Tupper, B. O. J.

    1992-05-01

    All space-times admitting a proper affine conformal vector (ACV) are found. By using a theorem of Hall and da Costa, it is shown that such space-times either (i) admit a covariantly constant vector (timelike, spacelike, or null) and the ACV is the sum of a proper affine vector and a conformal Killing vector or (ii) the space-time is 2+2 decomposable, in which case it is shown that no ACV can exist (unless the space-time decomposes further). Furthermore, it is proved that all space-times admitting an ACV and a null covariantly constant vector (which are necessarily generalized pp-wave space-times) must have Ricci tensor of Segré type {2,(1,1)}. It follows that, among space-times admitting proper ACV, the Einstein static universe is the only perfect fluid space-time, there are no non-null Einstein-Maxwell space-times, and only the pp-wave space-times are representative of null Einstein-Maxwell solutions. Otherwise, the space-times can represent anisotropic fluids and viscous heat-conducting fluids, but only with restricted equations of state in each case.

  15. 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

  16. Motivational maturity and helping behavior.

    Science.gov (United States)

    Haymes, M; Green, L

    1977-12-01

    This study was undertaken to examine the independent influences of conative development (the Maslow needs hierarchy) upon behavioral aspects of prosocial orientations. It provides a behavioral demonstration of conative effects in a helping paradigm, among college-age men. A comparison of the conative data across the ages of 15-22 provided a cross-sectional view of conative development itself. Conative maturity was found to be predictive of greater helping among college-age men. Situational demands were demonstrated which tended to mask, but not override, these predispositional influences on helping. The cross-sectional data on conative development point to probable movement to early esteem concerns among high school men who have reached the conative level of love and belonging. On the other hand, the stability across the years of 15-22 of proportion of safety concerns suggests fixation of such concerns in those exhibiting them in high school. Results are discussed in terms of conative growth for development of prosocial orientations.

  17. 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

  18. 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

  19. 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.

  20. 7 CFR 51.1865 - Mature.

    Science.gov (United States)

    2010-01-01

    ... FRESH FRUITS, VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) United States Standards for Fresh Tomatoes 1 Definitions § 51.1865 Mature. Mature means that the tomato has reached the stage of development which will insure a proper completion of the ripening process, and that...

  1. 7 CFR 51.1907 - Mature.

    Science.gov (United States)

    2010-01-01

    ... FRESH FRUITS, VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) United States Consumer Standards for Fresh Tomatoes Definitions § 51.1907 Mature. Mature means that the tomato has reached the stage of development which will insure a proper completion of the ripening process....

  2. Decision-Making Style and Vocational Maturity.

    Science.gov (United States)

    Phillips, Susan D.; Strohmer, Douglas C.

    1982-01-01

    Examined the relationship between decision-making style, scholastic achievement, and vocational maturity for college students (N=64). Results did not support the hypothesized relationship between rationality and attitudinal and cognitive maturity. Scholastic achievement and lack of dependent decision style were found to be moderately predictive of…

  3. 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…

  4. Motivation and Maturity Patterns in Marital Success.

    Science.gov (United States)

    McClelland, David C.; And Others

    1978-01-01

    Married couples rated their marital satisfaction and played interpersonal competitive games which revealed the success with which they interacted. Younger husbands who scored more maturely on the Stewart measure of psychosocial maturity belonged to more successful marriages, as did college-educated wives who showed less immaturity and more phallic…

  5. 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

  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......: the Design Audit to assess product development capabilities and the Communication Grid Method to assess communication in product development. As maturity grid assessments are not just performance measures but also mechanisms for change, in developing and applying maturity grid assessments, the consultants...

  7. 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...

  8. Affine and Projective Tree Metric Theorems

    CERN Document Server

    Harel, Matan; Pachter, Lior

    2011-01-01

    The tree metric theorem provides a combinatorial four point condition that characterizes dissimilarity maps derived from pairwise compatible split systems. A similar (but weaker) four point condition characterizes dissimilarity maps derived from circular split systems (Kalmanson metrics). The tree metric theorem was first discovered in the context of phylogenetics and forms the basis of many tree reconstruction algorithms, whereas Kalmanson metrics were first considered by computer scientists, and are notable in that they are a non-trivial class of metrics for which the traveling salesman problem is tractable. We present a unifying framework for these theorems based on combinatorial structures that are used for graph planarity testing. These are (projective) PC-trees, and their affine analogs, PQ-trees. In the projective case, we generalize a number of concepts from clustering theory, including hierarchies, pyramids, ultrametrics and Robinsonian matrices, and the theorems that relate them. As with tree metric...

  9. 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.

  10. 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.

  11. 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.

  12. Affine trajectory correction for nonholonomic mobile robots

    CERN Document Server

    Pham, Quang-Cuong

    2011-01-01

    Planning trajectories for nonholonomic systems is difficult and computationally expensive. When facing unexpected events, it may therefore be preferable to deform in some way the initially planned trajectory rather than to re-plan entirely a new one. We suggest here a method based on affine transformations to make such deformations. This method is exact and fast: the deformations and the resulting trajectories can be computed algebraically, in one step, and without any trajectory re-integration. To demonstrate the possibilities offered by this new method, we use it to derive position correction, orientation correction, obstacle avoidance and feedback control algorithms for the general class of planar wheeled robots and for a tridimensional underwater vehicle.

  13. Indefinite Affine Hyperspheres Admitting a Pointwise Symmetry. Part 2

    Directory of Open Access Journals (Sweden)

    Christine Scharlach

    2009-10-01

    Full Text Available An affine hypersurface M is said to admit a pointwise symmetry, if there exists a subgroup G of Aut(T_pM for all p in M, which preserves (pointwise the affine metric h, the difference tensor K and the affine shape operator S. Here, we consider 3-dimensional indefinite affine hyperspheres, i.e. S = HId (and thus S is trivially preserved. In Part 1 we found the possible symmetry groups G and gave for each G a canonical form of K. We started a classification by showing that hyperspheres admitting a pointwise Z_2 × Z_2 resp. R-symmetry are well-known, they have constant sectional curvature and Pick invariant J < 0 resp. J = 0. Here, we continue with affine hyperspheres admitting a pointwise Z_3- or SO(2-symmetry. They turn out to be warped products of affine spheres (Z_3 or quadrics (SO(2 with a curve.

  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. Abacus models for parabolic quotients of affine Weyl groups

    CERN Document Server

    Hanusa, Christopher R H

    2011-01-01

    We introduce abacus diagrams that describe minimal length coset representatives in affine Weyl groups of types B, C, and D. These abacus diagrams use a realization of the affine Weyl group of type C due to Eriksson to generalize a construction of James for the symmetric group. We also describe several combinatorial models for these parabolic quotients that generalize classical results in affine type A related to core partitions.

  16. 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

  17. 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.

  18. 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....

  19. 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.

  20. 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...

  1. Hypothalamic control of the mammalian sexual maturation.

    Science.gov (United States)

    Gupta, D

    1977-01-01

    The attainment of sexual maturity is a complex process which requires maturation and interaction not only of gonads and reproductive tract but also of the pituitary and essentially of the neuroendocrine mechanisms which ultimately control gonadotropin secretion. One of the more attractive hypotheses of the sexual maturation presumes the existence of the sensitivity threshold of the regulating system to the negative feedback signal, which differentiates immaturity from maturity. As the subject matures this declines. In an attempt to examine further the maturational alterations of the male hypothalamo-pituitary-gonadal axis, investigations were carried out with regard to simultaneous changes of blood LH, FSH, testosterone and dihydrotestosterone levels during the course of 24 hr; augmentation of pituitary and blood LH and FSH concentrations under the stimulus of LH-RH as a function of time and age; synthesis and release of LH and FSH in the testosterone-blocked animals at various stages of sexual maturation; and in vitro biotransformation of testosterone to its 5 alpha-reduced metabolites by the pituitaries as a function of age. Evidence from the experimental data could be interpreted as a decrement of the feedback set-points during sexual maturatio as reflected by the transition of the responses obtained under various experimental signals. In parallel to these observations, new evidence was presented regarding not only quantitative but qualitative changes in the pituitary gonadotropins as response to the negative and positive feedback signals. This leads to new thinking with regard to the hypothesis of differential sensitivity.

  2. Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells.

    NARCIS (Netherlands)

    Schreibelt, G.; Benitez-Ribas, D.; Schuurhuis, D.; Lambeck, A.J.A.; Hout-Kuijer, M.A. van; Schaft, N.; Punt, C.J.A.; Figdor, C.G.; Adema, G.J.; Vries, I.J.M. de

    2010-01-01

    Currently dendritic cell (DC)-based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limite

  3. 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...

  4. 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...

  5. 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.

  6. The cohomology of the affine Deligne-Lusztig varieties in the affine flag manifold of $GL_2$

    CERN Document Server

    Ivanov, Alexander

    2009-01-01

    This paper studies affine Deligne-Lusztig varieties in the affine flag manifold of GL_2. At first we determine all such varieties up to isomorphy. After this we investigate the representations of the sigma-stabilizer of an element b of the group on the etale cohomology of the affine Deligne-Lusztig variety X_w(b). We describe such representations as inductions from compact subgroups and in terms of noncuspidal representations.

  7. 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.

  8. 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 .

  9. Evolution of green coffee protein profiles with maturation and relationship to coffee cup quality.

    Science.gov (United States)

    Montavon, Philippe; Duruz, Eliane; Rumo, Gilbert; Pratz, Gudrun

    2003-04-01

    Coffee flavor is the product of a complex chain of chemical transformations. The green bean has only a faint odor that is not at all reminiscent of coffee aroma. It contains, however, all of the necessary precursors to generate the unmistakable coffee flavor during roasting. The levels and biochemical status of these precursors may vary in relation to genetic traits, environmental factors, maturation level, postharvest treatment, and storage. To improve our understanding of coffee flavor generation, the sensory and biochemical impact of maturation was assessed. Maturation clearly favored the development of high-quality flavor in the coffee brew. A specific subclass of green coffee beans, however, generated high-quality coffee flavor irrespective of maturation. Biochemical aspects were examined using a dynamic system: immature and mature green coffee suspensions were incubated under air or argon. On the analytical side, a specific pool of flavor precursors was monitored: chlorogenic acids, green coffee proteins, and free amino acids. A link between maturation, the redox behavior of green coffee suspensions, and their sensory scores was identified. Compared to ripe beans, unripe beans were found to be more sensitive to oxidation of chlorogenic acids. Aerobic incubation also triggered the fragmentation or digestion of the 11S seed storage protein and the release of free amino acids. PMID:12670177

  10. 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.

  11. 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

  12. Two-parameter quantum affine algebra of type G{sub 2}{sup (1)}, Drinfeld realization and vertex representation

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yun, E-mail: ygao@yorku.ca [Department of Mathematics and Statistics, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3 (Canada); Hu, Naihong, E-mail: nhhu@math.ecnu.edu.cn [Department of Mathematics, East China Normal University, Shanghai 200241 (China); Zhang, Honglian, E-mail: hlzhangmath@shu.edu.cn [Department of Mathematics, Shanghai University, Shanghai 200444 (China)

    2015-01-15

    In this paper, we define the two-parameter quantum affine algebra for type G{sub 2}{sup (1)} and give the (r, s)-Drinfeld realization of U{sub r,s}(G{sub 2}{sup (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 U{sub r,s}(G{sub 2}{sup (1)}), which also supports an evidence in nontwisted type G{sub 2}{sup (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 U{sub r,s}(g{sup ^}): Simply laced cases e-print http://arxiv.org/abs/1401.4925 ].

  13. 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...

  14. The Moral Maturity of Repeater Delinquents.

    Science.gov (United States)

    Petronio, Richard J.

    1980-01-01

    Differences in moral development (as conceived by Kohlberg) were examined in a sample of delinquent teenagers. The repeater group was not found, as had been hypothesized, to be lower on moral maturity than those who engaged in less delinquency. (GC)

  15. Bighead carp - its maturation and ovulation

    OpenAIRE

    1996-01-01

    The paper investigates the effects of intraperitoneal injections of LHRH-a and domperidone (DOM), given singly or in combination at two injections, on oocyte maturation and spawning in bighead carp, Aristichthys nobilis.

  16. 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"...

  17. 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…

  18. Isolation of bovine serum albumin from whey using affinity chromatography

    NARCIS (Netherlands)

    Besselink, T.; Janssen, A.E.M.; Boom, R.M.

    2015-01-01

    The adsorption of bovine serum albumin (BSA) to a chromatography resin with immobilised llama antibody fragments as affinity ligands was investigated. The maximum adsorption capacity of the affinity resin was 21.6 mg mL-1 with a Langmuir equilibrium constant of 20.4 mg mg-1. Using packed bed chromat

  19. 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.

  20. Capillary electrophoresis-based assessment of nanobody affinity and purity

    NARCIS (Netherlands)

    Haselberg, Rob; Oliveira, Sabrina; van der Meel, Roy; Somsen, Govert W; de Jong, Gerhardus J

    2014-01-01

    Drug purity and affinity are essential attributes during development and production of therapeutic proteins. In this work, capillary electrophoresis (CE) was used to determine both the affinity and composition of the biotechnologically produced "nanobody" EGa1, the binding fragment of a heavy-chain-

  1. 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

  2. Frame-independent mechanics:geometry on affine bundles

    OpenAIRE

    Grabowska, K.; Grabowski, J.; Urbanski, P.

    2005-01-01

    Main ideas of the differential geometry on affine bundles are presented. Affine counterparts of Lie algebroid and Poisson structures are introduced and discussed. The developed concepts are applied in a frame-independent formulation of the time-dependent and the Newtonian mechanics.

  3. Peptide Nucleic Acids Having Enhanced Binding Affinity and Sequence Specificity

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. Methods of increasing binding affinity and sequence specificity of peptide nucleic aci...

  4. High affinity retinoic acid receptor antagonists: analogs of AGN 193109.

    Science.gov (United States)

    Johnson, A T; Wang, L; Gillett, S J; Chandraratna, R A

    1999-02-22

    A series of high affinity retinoic acid receptor (RAR) antagonists were prepared based upon the known antagonist AGN 193109 (2). Introduction of various phenyl groups revealed a preference for substitution at the para-position relative to the meta-site. Antagonists with the highest affinities for the RARs possessed hydrophobic groups, however, the presence of polar functionality was also well tolerated.

  5. 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...

  6. 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 ...

  7. 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

  8. Affinity Monolith-Integrated Microchips for Protein Purification and Concentration.

    Science.gov (United States)

    Gao, Changlu; Sun, Xiuhua; Wang, Huaixin; Qiao, Wei; Hu, Bo

    2016-01-01

    Affinity chromatography is a valuable method to purify and concentrate minute amount of proteins. Monoliths with epoxy groups for affinity immobilization were prepared by direct in-situ photopolymerization of glycidyl methacrylate and ethylene glycol dimethacrylate in porogenic solvents consisting of 1-dodecanol and cyclohexanol. By integrating affinity monoliths onto a microfluidic system, targeted biomolecules can be captured and retained on affinity column, while other biomolecules having no specific interactions toward the immobilized ligands flow through the microchannel. Therefore, proteins which remain on the affinity column are purified and concentrated, and then eluted by appropriate solutions and finally, separated by microchip capillary electrophoresis. This integrated microfluidic device has been applied to the purification and separation of specific proteins (FITC-labeled human serum albumin and IgG) in a mixture.

  9. Detection of protein-protein interactions using tandem affinity purification.

    Science.gov (United States)

    Goodfellow, Ian; Bailey, Dalan

    2014-01-01

    Tandem affinity purification (TAP) is an invaluable technique for identifying interaction partners for an affinity tagged bait protein. The approach relies on the fusion of dual tags to the bait before separate rounds of affinity purification and precipitation. Frequently two specific elution steps are also performed to increase the specificity of the overall technique. In the method detailed here, the two tags used are protein G and a short streptavidin binding peptide; however, many variations can be employed. In our example the tags are separated by a cleavable tobacco etch virus protease target sequence, allowing for specific elution after the first round of affinity purification. Proteins isolated after the final elution step in this process are concentrated before being identified by mass spectrometry. The use of dual affinity tags and specific elution in this technique dramatically increases both the specificity and stringency of the pull-downs, ensuring a low level of background nonspecific interactions.

  10. 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

  11. Dynamics of Nucleosome Positioning Maturation following Genomic Replication.

    Science.gov (United States)

    Vasseur, Pauline; Tonazzini, Saphia; Ziane, Rahima; Camasses, Alain; Rando, Oliver J; Radman-Livaja, Marta

    2016-09-01

    Chromatin is thought to carry epigenetic information from one generation to the next, although it is unclear how such information survives the disruptions of nucleosomal architecture occurring during genomic replication. Here, we measure a key aspect of chromatin structure dynamics during replication-how rapidly nucleosome positions are established on the newly replicated daughter genomes. By isolating newly synthesized DNA marked with 5-ethynyl-2'-deoxyuridine (EdU), we characterize nucleosome positions on both daughter genomes of S. cerevisiae during chromatin maturation. We find that nucleosomes rapidly adopt their mid-log positions at highly transcribed genes, which is consistent with a role for transcription in positioning nucleosomes in vivo. Additionally, experiments in hir1Δ mutants reveal a role for HIR in nucleosome spacing. We also characterized nucleosome positions on the leading and lagging strands, uncovering differences in chromatin maturation dynamics at hundreds of genes. Our data define the maturation dynamics of newly replicated chromatin and support a role for transcription in sculpting the chromatin template. PMID:27568571

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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...

  17. 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...

  18. 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...

  19. 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

  20. An affinity-directed protein missile system for targeted proteolysis

    Science.gov (United States)

    Fulcher, Luke J.; Macartney, Thomas; Bozatzi, Polyxeni; Hornberger, Annika; Rojas-Fernandez, Alejandro

    2016-01-01

    The von Hippel–Lindau (VHL) protein serves to recruit the hypoxia-inducible factor alpha (HIF1α) protein under normoxia to the CUL2 E3 ubiquitin ligase for its ubiquitylation and degradation through the proteasome. In this report, we modify VHL to engineer an affinity-directed protein missile (AdPROM) system to direct specific endogenous target proteins for proteolysis in mammalian cells. The proteolytic AdPROM construct harbours a cameloid anti-green fluorescence protein (aGFP) nanobody that is fused to VHL for either constitutive or tetracycline-inducible expression. For target proteins, we exploit CRISPR/Cas9 to rapidly generate human kidney HEK293 and U2OS osteosarcoma homozygous knock-in cells harbouring GFP tags at the VPS34 (vacuolar protein sorting 34) and protein associated with SMAD1 (PAWS1, aka FAM83G) loci, respectively. Using these cells, we demonstrate that the expression of the VHL-aGFP AdPROM system results in near-complete degradation of the endogenous GFP-VPS34 and PAWS1-GFP proteins through the proteasome. Additionally, we show that Tet-inducible destruction of GFP-VPS34 results in the degradation of its associated partner, UVRAG, and reduction in levels of cellular phosphatidylinositol 3-phosphate. PMID:27784791

  1. 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

  2. Optimal affine-invariant matching: performance characterization

    Science.gov (United States)

    Costa, Mauro S.; Haralick, Robert M.; Shapiro, Linda G.

    1992-04-01

    The geometric hashing scheme proposed by Lamdan and Wolfson can be very efficient in a model-based matching system, not only in terms of the computational complexity involved, but also in terms of the simplicity of the method. In a recent paper, we discussed errors that can occur with this method due to quantization, stability, symmetry, and noise problems. These errors make the original geometric hashing technique unsuitable for use on the factory floor. Beginning with an explicit noise model, which the original Lamdan and Wolfson technique lacks, we derived an optimal approach that overcomes these problems. We showed that the results obtained with the new algorithm are clearly better than the results from the original method. This paper addresses the performance characterization of the geometric hashing technique, more specifically the affine-invariant point matching, applied to the problem of recognizing and determining the pose of sheet metal parts. The experiments indicate that with a model having 10 to 14 points, with 2 points of the model undetected and 10 extraneous points detected, and with the model points perturbed by Gaussian noise of standard deviation 3 (0.58 of range), the average amount of computation required to obtain an answer is equivalent to trying 11 of the possible three-point bases. The misdetection rate, measured by the percentage of correct bases matches that fail to verify, is 0.9. The percentage of incorrect bases that successfully produced a match that did verify (false alarm rate) is 13. And, finally, 2 of the experiments failed to find a correct match and verify it. Results for experiments with real images are also presented.

  3. 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

  4. 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

  5. Screening for oligonucleotide binding affinity by a convenient fluorescence competition assay.

    Science.gov (United States)

    Harrison, J G; Liu, X; Balasubramanian, S

    1999-09-01

    A competitive homogeneous quenched fluorescence assay system is described for the high throughput screening of DNA conjugates that bind to single-stranded DNA. Fluorescence signal is generated by competitive binding of the sample molecule to a target strand labelled with a quencher probe, which is otherwise hybridised to a complementary strand containing a fluorescent probe. Thus fluorescence generated is related to the affinity of the sample. Competitive analysis of a number of peptide-oligonucleotide conjugates gave data that correlated well with the corresponding UV melting data. The assay will be useful for screening of large numbers of potential single-stranded binding molecules.

  6. 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.

  7. 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....... 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Horiuchi-Suzuki, Kazuko [Development Bureau, Hamamatsu Photonics K.K., Hirakuchi 500, 434-8601, Hamakita City (Japan); Konno, Aya; Ueda, Mayumi; Fukuda, Yoko; Nishio, Saori; Saji, Hideo [Graduate School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto (Japan); Hashimoto, Kazuyuki [Department of Radioisotope Production, Japan Energy Research Institute, Ibaraki-ken, Tokai-mura (Japan)

    2004-03-01

    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.)

  9. 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...

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    Gilberto Zanoni

    2013-05-01

    Full Text Available 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 evolution stages of the supplier-purchaser relationship. This model integrates a measuring system based on the ‘Performance Prism’. The model is tested in enterprises of the automotive industry. The methodology used to test and validate the model is a survey. Results stated that the participant enterprises are generally found in maturity level 3, which is also confirmed by cluster analysis. Maturity level models may help companies in evolutionary trajectories stating references for their change processes.

  13. The sodium ion affinities of asparagine, glutamine, histidine and arginine

    Science.gov (United States)

    Wang, Ping; Ohanessian, Gilles; Wesdemiotis, Chrys

    2008-01-01

    The sodium ion affinities of the amino acids Asn, Gln, His and Arg have been determined by experimental and computational approaches (for Asn, His and Arg). Na+-bound heterodimers with amino acid and peptide ligands (Pep1, Pep2) were produced by electrospray ionization. From the dissociation kinetics of these Pep1-Na+-Pep2 ions to Pep1-Na+ and Pep2-Na+, determined by collisionally activated dissociation, a ladder of relative affinities was constructed and subsequently converted to absolute affinities by anchoring the relative values to known Na+ affinities. The Na+ affinities of Asn, His and Arg, were calculated at the MP2(full)/6-311+G(2d,2p)//MP2/6-31G(d) level of ab initio theory. The resulting experimental and computed Na+ affinities are in excellent agreement with one another. These results, combined with those of our previous studies, yield the sodium ion affinities of 18 out of the 20 [alpha]-amino acids naturally occurring in peptides and proteins of living systems.

  14. 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.

  15. 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

  16. Asymptotics of generalized Galois numbers via affine Kac-Moody algebras

    CERN Document Server

    Kousidis, Stavros

    2011-01-01

    Generalized Galois numbers count the number of flags in vector spaces over finite fields. Asymptotically, as the dimension of the vector space becomes large, we give their exponential growth and determine their initial values. The initial values are expressed analytically in terms of theta functions and Euler's generating function for the partition numbers. Our asymptotic enumeration method is based on a Demazure module limit construction for integrable highest weight representations of affine Kac-Moody algebras. For the classical Galois numbers, that count the number of subspaces in vector spaces over finite fields, the theta functions are Jacobi theta functions. We apply our findings to the asymptotic number of q-ary codes, and conclude with some final remarks about possible future research concerning asymptotic enumerations via limit constructions for affine Kac-Moody algebras.

  17. 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).

  18. A q-Analogue of the Centralizer Construction and Skew Representations of the Quantum Affine Algebra

    Directory of Open Access Journals (Sweden)

    Mark J. Hopkins

    2006-12-01

    Full Text Available We prove an analogue of the Sylvester theorem for the generator matrices of the quantum affine algebra ${ m U}_q(widehat{mathfrak{gl}}_n$. We then use it to give an explicit realization of the skew representations of the quantum affine algebra. This allows one to identify them in a simple way by calculating their highest weight, Drinfeld polynomials and the Gelfand-Tsetlin character (or $q$-character. We also apply the quantum Sylvester theorem to construct a$q$-analogue of the Olshanski algebra as a projective limit of certaincentralizers in ${ m U}_q(mathfrak{gl}_n$ and show that this limit algebra contains the $q$-Yangian as a subalgebra.

  19. 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 ...

  20. 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...... 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...

  1. Non-Gatherable Triples for Non-Affine Root Systems

    Directory of Open Access Journals (Sweden)

    Ivan Cherednik

    2008-11-01

    Full Text Available This paper contains a complete description of minimal non-gatherable triangle triples in the lambda-sequences for the classical root systems, $F_4$ and $E_6$. Such sequences are associated with reduced decompositions (words in affine and non-affine Weyl groups. The existence of the non-gatherable triples is a combinatorial obstacle for using the technique of intertwiners for an explicit description of the irreducible representations of the (double affine Hecke algebras, complementary to their algebraic-geometric theory.

  2. 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.

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Katsushi; Locke, Christopher

    2014-08-15

    We study the two-dimensional affine Toda field equations for affine Lie algebra g{sup ^} 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 g{sup ^}, we obtain a (pseudo-)differential equation corresponding to the Bethe equations for the Langlands dual of the Lie algebra g, which were found by Dorey et al. in study of the ODE/IM correspondence.

  5. 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;

    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....... Screening of 1 against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-1 binding shows high specificity to the high-affinity GHB binding sites....

  6. 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

  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. [Relationship between sexual maturation and subcutaneous fat].

    Science.gov (United States)

    García Llop, L A; Ramada Benedito, A; Rodríguez-Estecha, P

    1990-10-01

    Due to the great variability at the beginnings and the period of the puberty, authors have studied the modifications of the subcutaneous-fat and their relation with the sexual maturating. They have measured the skinfold thickness of biceps, triceps, subscapular and suprailiac in 358 boys from 10 to 15 years old and 424 girls from 8 to 14 years old inrelation to sexual maturating through the stages described by Tanner. It has been found more subcutaneous fat in girls than in boys (p less than 0.05). The boys increase their subcutaneous fat until the stage 3 (except the skinfold triceps) and decrease later (except the skinfold subscapular). In boys, the analysis of varianza, show that the variations are related with the sexual maturating and not with chronologic age. PMID:2278437

  9. 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.

  10. Robotic QM/MM-driven maturation of antibody combining sites

    Science.gov (United States)

    Smirnov, Ivan V.; Golovin, Andrey V.; Chatziefthimiou, Spyros D.; Stepanova, Anastasiya V.; Peng, Yingjie; Zolotareva, Olga I.; Belogurov, Alexey A.; Kurkova, Inna N.; Ponomarenko, Natalie A.; Wilmanns, Matthias; Blackburn, G. Michael; Gabibov, Alexander G.; Lerner, Richard A.

    2016-01-01

    In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents. Virtual screening of 167,538 robotically generated mutants identified an optimum single point mutation, which experimentally boosted wild-type Ig scavenger performance by 170-fold. We validated the QM/MM predictions via kinetic analysis and crystal structures of mutant apo-A17 and covalently modified Ig, thereby identifying the displacement of one water molecule by an arginine as delivering this catalysis. PMID:27774510

  11. 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

  12. 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...

  13. 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

  14. 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...

  15. Management and Breeding Soundness of Mature Bulls.

    Science.gov (United States)

    Palmer, Colin W

    2016-07-01

    Mature bulls must be fed a balanced ration, vaccinated appropriately, and undergo a breeding soundness evaluation to ensure they meet what is required of a short, but intense breeding season. To be classified as a satisfactory potential breeder, minimum standards for physical soundness, scrotal circumference, sperm motility, and sperm morphology must be achieved using an accepted bull-breeding soundness evaluation format. Sperm production requires approximately 70 days. Heat and stress are the most common insults to spermatogenesis, causing an increase in morphologic abnormalities with obesity-associated scrotal fat accumulation being the most frequent cause of elevated testicular temperature in mature bulls.

  16. 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

  17. 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.

  18. Asset Stripping in a Mature Market Economy

    DEFF Research Database (Denmark)

    Klarskov Jeppesen, Kim; Møller, Ulrik Gorm

    2011-01-01

    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...... is to analyse why the asset-stripping schemes occurred in a mature market economy with a strong corporate governance system and a low level of corruption. Design/methodology/approach – The research is conducted as a longitudinal single case study based on documentary research. Findings – The Danish case...

  19. Properties of an affine transport equation and its generalized holonomy

    CERN Document Server

    Vines, Justin

    2014-01-01

    We investigate properties of a transport equation that was recently used to study the observer dependence of angular momentum in general relativity. The associated map between the tangent spaces at two points on a curve is affine, and for this reason, the operation was called "affine transport". The map consists of a homogeneous (linear) part given by the parallel transport map along the curve, plus an inhomogeneous part which is related to the development of a curve in a manifold into an affine tangent space (also described as the rolling of a manifold along a tangent space without slipping or twisting). For closed curves, the affine transport equation defines a "generalized holonomy". We use covariant bitensor calculus to compute the generalized holonomy around geodesic polygon loops, specifically for triangles and "parallelogramoids" with sides formed from geodesic segments. For small loops, we recover the well-known result for the leading-order holonomy of parallel transport ($\\sim$ Riemann $\\times$ area)...

  20. Elective affinities and economic thought: 1870-1914

    Directory of Open Access Journals (Sweden)

    João Antônio de Paula

    2006-01-01

    Full Text Available This article seeks to demonstrate that the concept of "elective affinities" can be applied to the relations between economic thought, literature, and philosophy. Emphasis is given to Institutionalist thought, the German historical school, and neoclassical thought.

  1. Experimental investigation of streamer affinity for dielectric surfaces

    OpenAIRE

    Trienekens, Dirk; Nijdam, Sander; Akkermans, G.; Plompen, I.; Christen, T.; Ebert, Ute

    2015-01-01

    We have experimentally investigated the affinity of streamers for dielectric surfaces using stroboscopic imaging and stereo photography. Affinity of streamers for dielectric surfaces was found to depend on a wide set of parameters, including pressure, voltage, dielectric material and discharge gap geometry. Our results show that higher relative permittivity, higher pressure, lower voltage, an d asymmetrical sample placement increase the chance of the streamer following the dielectric surface.

  2. A Characterization of Hyperbolic Affine Iterated Function Systems

    CERN Document Server

    Atkins, Ross; Vince, Andrew; Wilson, David C

    2009-01-01

    The two main theorems of this paper provide a characterization of hyperbolic affine iterated function systems defined on Rm. Atsushi Kameyama (Distances on Topological Self-Similar Sets, Proceedings of Symposia in Pure Mathematics, Volume 72.1, 2004) asked the following fundamental question: given a topological self-similar set, does there exist an associated system of contraction mappings? Our theorems imply an affirmative answer to Kameyama's question for self-similar sets derived from affine transformations on Rm.

  3. 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.

  4. Some Inequalities for Lp-mixed Affine Surface Area

    Institute of Scientific and Technical Information of China (English)

    ZHU Xian-yang

    2012-01-01

    In this paper,the concepts of the ith Lp-mixed affine surface area and Lp-polar curvature images are introduced,some new inequalities connecting these new notions with Lp-centroid bodies and p-Blaschke bodies are showed.Moreover,a Blaschke-Santaló type inequality for Lp-mixed affine surface area is established.Our results also imply the similar to the inequalities for Marcus-Lopes,Bergstrom and Ky Fan.

  5. 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...

  6. 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...

  7. 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,...

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Development of an automated mid-scale parallel protein purification system for antibody purification and affinity chromatography.

    Science.gov (United States)

    Zhang, Chi; Long, Alexander M; Swalm, Brooke; Charest, Ken; Wang, Yan; Hu, Jiali; Schulz, Craig; Goetzinger, Wolfgang; Hall, Brian E

    2016-12-01

    Protein purification is often a bottleneck during protein generation for large molecule drug discovery. Therapeutic antibody campaigns typically require the purification of hundreds of monoclonal antibodies (mAbs) during the hybridoma process and lead optimization. With the increase in high-throughput cloning, faster DNA sequencing, and the use of parallel protein expression systems, a need for high-throughput purification approaches has evolved, particularly in the midsize range between 20 ml and 100 ml. To address this we modified a four channel Gilson solid phase extraction system (referred to as MG-SPE) with switching valves and sample holding loops to be able to perform standard affinity purification using commercially available columns and micro-titer format deep well blocks. By running 4 samples in parallel, the MG-SPE has the capacity to purify up to 24 samples of greater than 50 ml each using a single-step affinity purification protocol or a two-step protocol consisting of affinity chromatography followed by desalting/buffer exchange overnight (∼12 h run time). Our evaluation of affinity purification using mAbs and Fc-fusion proteins from mammalian cell supernatants demonstrates that the MG-SPE compared favorably with industry standard systems for both protein quality and yield. Overall the system is simple to operate and fills a void in purification processes where a simple, efficient, automated system is needed for affinity purification of midsize research samples.

  13. An inactivating mutation within the first extracellular loop of the thyrotropin receptor impedes normal posttranslational maturation of the extracellular domain.

    Science.gov (United States)

    Sura-Trueba, Sylvia; Aumas, Chantal; Carre, Aurore; Durif, Sylvie; Leger, Juliane; Polak, Michel; de Roux, Nicolas

    2009-02-01

    The TSH receptor (TSHR), a member of the large family of G protein-coupled receptors, controls both function and growth of thyroid cells; hence, mutations of this receptor result in thyroid dysfunction. Here, we took advantage of the description of a new inactivating TSHR mutation (Q489H) in two brothers with hypothyroidism, to precise maturation, intracellular trafficking, exporting pathways, and activation mechanisms of this receptor. Functional characterization of the Q489H-TSHR in transiently transfected HEK293 cells showed cell surface expression, normal TSH binding affinity, and its inability to generate intracellular cAMP in response to TSH stimulation. Western blot analysis of the whole membrane proteins or proteins expressed at the cell surface showed that Q489H-TSHR expressed in HEK293 transfected cells are restricted to mannose-rich uncleaved receptor. Analysis of the export pathway toward cell surface indicated that both Q489H and wild-type receptors followed the same intracellular route to cell surface throughout endoplasmic reticulum and Golgi apparatus. This study shows that Q489H substitution impedes complete glycosylation of TSHR extracellular domain within the Golgi apparatus and that Q489H-TSHR expressed at the cell surface is unable to undergo intramolecular cleavage as well as to switch toward an active conformation under TSH stimulation. Altogether, our results show that 1) Q489H substitution within the first extracellular loop induces a misfolding of TSHR, blocking it into an inactive conformation and impeding complete glycosylation and intramolecular cleavage, and 2) a misfolded G protein-coupled receptor can bypass endoplasmic reticulum or Golgi apparatus quality control and reach the cell surface as an immature receptor. PMID:18927215

  14. 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

  15. 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 ...

  16. 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.

  17. Teaching Copywriting Students about the Mature Market.

    Science.gov (United States)

    Drewniany, Bonnie

    Advertising educators have a responsibility to make students aware of the importance of the mature market (older people) and to teach them methods to reach this group. An assignment in a copywriting class asked students to write and design ads to promote blue jeans to adults over 50. The assignment accomplished three things: (1) helped students…

  18. 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)

  19. 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.

  20. Spotlight on Shanxi very mature vinegar

    Institute of Scientific and Technical Information of China (English)

    Shan Fang; Wang Lixia; Li Wende

    2005-01-01

    @@ There are four kinds of the most famous vinegars in China. Qingxu Very Mature Vinegar of Shanxi Province is number one. Three others are Zhenjiang Savory Vinegar of Jiangsu Province, Baoning Bran Vinegar of Sichuan Province and Yongchun Vinegar of Fujian Province.

  1. Evaluating Hass Avocado Maturity Using Hyperspectral Imaging

    Science.gov (United States)

    The maturity of avocado fruit is usually assessed by measuring its dry matter content(DM), which is a destructive and time consuming process. The aim of this study is tointroduce a non-destructive and quick technique that can estimate the DM content of an avocado fruit. 'Hass' avocado fruits at diff...

  2. Relative dental maturity and associated skeletal maturity in prehistoric native Americans of the Ohio valley area.

    Science.gov (United States)

    Sciulli, Paul W

    2007-04-01

    Estimation of age-at-death of subadults in prehistoric skeletal samples based on modern reference standards rests on a number of assumptions of which many are untestable. If these assumptions are not met error of unknown magnitude and direction will be introduced to the subadult age estimates. This situation suggests that an independent estimate or estimates of age-related features, free of most of the assumptions made when using modern reference standards may be useful supplements in evaluating the age of subadults in prehistoric samples. The present study provides an internally consistent, population-specific measure of maturity for prehistoric Ohio valley Native Americans based on the seriation of dental development that may be used as a supplement to age-estimation. The developing dentition of 581 subadults from eight Ohio valley prehistoric-protohistoric groups was seriated within and among individuals resulting in a sequence of tooth development and a sequence of individuals from least to most mature. Dental maturity stages or sorting categories were then defined based on exclusive, easily observable, and highly repeatable tooth-formation stages. Tooth eruption (into occlusion), bone lengths, and fusion of skeletal elements are summarized by dental maturity stage. This procedure provides maturity estimates for skeletal features ordered by dental maturity stages derived from the same sample thus making explicit the relationship between dental and skeletal maturity.

  3. 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.

  4. Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma

    Science.gov (United States)

    Zhang, Yi-Fan; Ho, Mitchell

    2016-01-01

    Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell-mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer. PMID:27667400

  5. 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

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

    DEFF Research Database (Denmark)

    Svane, I M; Nikolajsen, K; Walter, M R;

    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...

  7. Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation

    NARCIS (Netherlands)

    Alvarez-Dominguez, Juan R; Hu, Wenqian; Yuan, Bingbing; Shi, Jiahai; Park, Staphany S; Gromatzky, Austin A; van Oudenaarden, Alexander; Lodish, Harvey F

    2014-01-01

    Erythropoiesis is regulated at multiple levels to ensure the proper generation of mature red cells under multiple physiological conditions. To probe the contribution of long noncoding RNAs (lncRNAs) to this process, we examined >1 billion RNA-seq reads of polyadenylated and nonpolyadenylated RNA fro

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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...

  16. 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.

  17. 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”.

  18. 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

  19. 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

  20. Respiration hastens maturation and lowers yield in rice.

    Science.gov (United States)

    Sitaramam, V; Bhate, R; Kamalraj, P; Pachapurkar, S

    2008-07-01

    Role of respiration in plant growth remains an enigma. Growth of meristematic cells, which are not photosynthetic, is entirely driven by endogenous respiration. Does respiration determine growth and size or does it merely burn off the carbon depleting the biomass? We show here that respiration of the germinating rice seed, which is contributed largely by the meristematic cells of the embryo, quantitatively correlates with the dynamics of much of plant growth, starting with the time for germination to the time for flowering and yield. Seed respiration appears to define the quantitative phenotype that contributes to yield via growth dynamics that could be discerned even in commercial varieties, which are biased towards higher yield, despite considerable susceptibility of the dynamics to environmental perturbations. Intrinsic variation, irreducible despite stringent growth conditions, required independent validation of relevant physiological variables both by critical sampling design and by constructing dendrograms for the interrelationships between variables that yield high consensus. More importantly, seed respiration, by mediating the generation clock time via variable time for maturation as seen in rice, directly offers the plausible basis for the phenotypic variation, a major ecological stratagem in a variable environment with uncertain water availability. Faster respiring rice plants appear to complete growth dynamics sooner, mature faster, resulting in a smaller plant with lower yield. Counter to the common allometric views, respiration appears to determine size in the rice plant, and offers a valid physiological means, within the limits of intrinsic variation, to help parental selection in breeding. PMID:23572892

  1. TLR-independent induction of dendritic cell maturation and adaptive immunity by negative-strand RNA viruses.

    Science.gov (United States)

    López, Carolina B; Moltedo, Bruno; Alexopoulou, Lena; Bonifaz, Laura; Flavell, Richard A; Moran, Thomas M

    2004-12-01

    TLR signaling leads to dendritic cell (DC) maturation and immunity to diverse pathogens. The stimulation of TLRs by conserved viral structures is the only described mechanism leading to DC maturation after a virus infection. In this report, we demonstrate that mouse myeloid DCs mature normally after in vivo and in vitro infection with Sendai virus (SeV) in the absence of TLR3, 7, 8, or 9 signaling. DC maturation by SeV requires virus replication not necessary for TLR-mediated triggering. Moreover, DCs deficient in TLR signaling efficiently prime for Th1 immunity after infection with influenza or SeV, generating IFN-gamma-producing T cells, CTLs and antiviral Abs. We have previously demonstrated that SeV induces DC maturation independently of the presence of type I IFN, which has been reported to mature DCs in a TLR-independent manner. The data presented here provide evidence for the existence of a novel intracellular pathway independent of TLR-mediated signaling responsible for live virus triggering of DC maturation and demonstrate its critical role in the onset of antiviral immunity. The revelation of this pathway should stimulate invigorating research into the mechanism for virus-induced DC maturation and immunity.

  2. 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

  3. Maturation of Fetal Responses to Music

    Science.gov (United States)

    Kisilevsky, B. S.; Hains, S. M. J.; Jacquet, A.-Y.; Granier-Deferre, C.; Lecanuet, J. P.

    2004-01-01

    Maturation of fetal response to music was characterized over the last trimester of pregnancy using a 5-minute piano recording of Brahms' Lullaby, played at an average of 95, 100, 105 or 110 dB (A). Within 30 seconds of the onset of the music, the youngest fetuses (28-32 weeks GA) showed a heart rate increase limited to the two highest dB levels;…

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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 ...

  9. RB975952 – Early maturing sugarcane cultivar

    Directory of Open Access Journals (Sweden)

    Monalisa Sampaio Carneiro

    2015-08-01

    Full Text Available RB975952 is an early maturing sugarcane cultivar released for the South-Central region of Brazil. It should be harvested between April and May, and it is recommended for planting in environments with medium to high production potential. RB975952 has high resistance levels to the main diseases of the crop, it also has a good shoot development after mechanical harvesting, and high sucrose yields.

  10. 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...

  11. Technology Maturation of Integrated System Health Management

    Science.gov (United States)

    Feather, Martin S.; Uckun, Serdar; Hicks, Kenneth A.

    2008-01-01

    Despite two decades of significant investments in R&D of Integrated System Health Management (ISHM), mission-critical applications of it in aerospace are few and far between. ISHM is subject to the general difficulty of transitioning technologies out of R&D labs and into practical applications. New and unproven methods such as ISHM introduce multiple mission risks (technology, schedule, cost), and may require a transition to unconventional and as-yet-unproven operations concepts in order to be effective. Laboratory and flight demonstrations are necessary but insufficient to adequately reduce those risks. What is needed is a solid business case before a new technology can be considered for fleetwide deployment. To address these problems, we recently applied a technology maturation assessment process developed at NASA's Jet Propulsion Laboratory to study the challenges of ISHM technology maturation. This application resulted in identification of the technologies (and technology maturation activities) that would result in the greatest risk reduction per investment dollar. Our approach and its results are described herein.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. 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 ...

  18. 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 inclu...... 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 C(I,L)? . . . . . . . . . . . . . . . . . . . . . . . . 160 4.6 Using weighted degree orderings . . . . . . . . . . . . . . . . . . . . . . . . . 163 4.7 The order domain conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 4.8 Weight functions and order domains...

  19. 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.

  20. Super-Affine Hierarchies and their Poisson Embeddings

    CERN Document Server

    Toppan, F

    1998-01-01

    The link between (super)-affine Lie algebras as Poisson brackets structures and integrable hierarchies provides both a classification and a tool for obtaining superintegrable hierarchies. The lack of a fully systematic procedure for constructing matrix-type Lax operators, which makes the supersymmetric case essentially different from the bosonic counterpart, is overcome via the notion of Poisson embeddings (P.E.), i.e. Poisson mappings relating affine structures to conformal structures (in their simplest version P.E. coincide with the Sugawara construction). A full class of hierarchies can be recovered by using uniquely Lie-algebraic notions. The group-algebraic properties implicit in the super-affine picture allow a systematic derivation of reduced hierarchies by imposing either coset conditions or hamiltonian constraints (or possibly both).

  1. 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.

  2. 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

  3. Quantitative Assessment of Cervical Vertebral Maturation Using Cone Beam Computed Tomography in Korean Girls

    Directory of Open Access Journals (Sweden)

    Bo-Ram Byun

    2015-01-01

    Full Text Available This study was aimed to examine the correlation between skeletal maturation status and parameters from the odontoid process/body of the second vertebra and the bodies of third and fourth cervical vertebrae and simultaneously build multiple regression models to be able to estimate skeletal maturation status in Korean girls. Hand-wrist radiographs and cone beam computed tomography (CBCT images were obtained from 74 Korean girls (6–18 years of age. CBCT-generated cervical vertebral maturation (CVM was used to demarcate the odontoid process and the body of the second cervical vertebra, based on the dentocentral synchondrosis. Correlation coefficient analysis and multiple linear regression analysis were used for each parameter of the cervical vertebrae (P<0.05. Forty-seven of 64 parameters from CBCT-generated CVM (independent variables exhibited statistically significant correlations (P<0.05. The multiple regression model with the greatest R2 had six parameters (PH2/W2, UW2/W2, (OH+AH2/LW2, UW3/LW3, D3, and H4/W4 as independent variables with a variance inflation factor (VIF of <2. CBCT-generated CVM was able to include parameters from the second cervical vertebral body and odontoid process, respectively, for the multiple regression models. This suggests that quantitative analysis might be used to estimate skeletal maturation status.

  4. 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.

  5. 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

  6. Affine group representation formalism for four dimensional, Lorentzian, quantum gravity

    CERN Document Server

    Ching-Yi, Chou; Soo, Chopin

    2012-01-01

    The Hamiltonian constraint of 4-dimensional General Relativity is recast explicitly in terms of the Chern--Simons functional and the local volume operator. In conjunction with the algebraic quantization program, application of the affine quantization concept due to Klauder facilitates the construction of solutions to all of the the quantum constraints in the Ashtekar variables and their associated Hilbert space. A physical Hilbert space is constructed for Lorentzian signature gravity with nonzero cosmological constant in the form of unitary, irreducible representations of the affine group.

  7. 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).

  8. 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.  

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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...

  14. 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.

  15. 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

  16. Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8.

    Science.gov (United States)

    Zhao, Qi; Ahmed, Mahiuddin; Guo, Hong-fen; Cheung, Irene Y; Cheung, Nai-Kong V

    2015-05-22

    Ganglioside GD2 is highly expressed on neuroectodermal tumors and an attractive therapeutic target for antibodies that have already shown some clinical efficacy. To further improve the current antibodies, which have modest affinity, we sought to improve affinity by using a combined method of random mutagenesis and in silico assisted design to affinity-mature the anti-GD2 monoclonal antibody hu3F8. Using yeast display, mutants in the Fv with enhanced binding over the parental clone were FACS-sorted and cloned. In silico modeling identified the minimal key interacting residues involved in the important charged interactions with the sialic acid groups of GD2. Two mutations, D32H (L-CDR1) and E1K (L-FR1) altered the electrostatic surface potential of the antigen binding site, allowing for an increase in positive charge to enhance the interaction with the negatively charged GD2-pentasaccharide headgroup. Purified scFv and IgG mutant forms were then tested for antigen specificity by ELISA, for tissue specificity by immunohistochemistry, for affinity by BIACORE, for antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity in vitro, and for anti-tumor efficacy in xenografted humanized mice. The nearly 7-fold improvement in affinity of hu3F8 with a single D32H (L-CDR1) mutation translated into a ∼12-fold improvement in NK92MI-transfected CD16-mediated ADCC, a 6-fold improvement in CD32-mediated ADCC, and a 2.5-fold improvement in complement-mediated cytotoxicity while maintaining restricted normal tissue cross-reactivity and achieving substantial improvement in tumor ablation in vivo. Despite increasing GD2 affinity, the double mutation D32H (L-CDR1) and E1K (L-FR1) did not further improve anti-tumor efficacy. PMID:25851904

  17. 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

  18. Characterization of the ER-Targeted Low Affinity Ca(2+) Probe D4ER.

    Science.gov (United States)

    Greotti, Elisa; Wong, Andrea; Pozzan, Tullio; Pendin, Diana; Pizzo, Paola

    2016-01-01

    Calcium ion (Ca(2+)) 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 Ca(2+) store and the free Ca(2+) concentration ([Ca(2+)]) within its lumen ([Ca(2+)]ER) can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca(2+) 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 Ca(2+) probes are plagued by different drawbacks, such as a double dissociation constant (Kd) for Ca(2+), low dynamic range, and an affinity for the cation that is too high for the levels of [Ca(2+)] 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 Ca(2+) affinity and dynamic range for monitoring [Ca(2+)] variations within the ER. As an example, resting [Ca(2+)]ER have been evaluated in a known paradigm of altered ER Ca(2+) homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer's Disease-linked protein Presenilin 2 (PS2). The lower Ca(2+) 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 Ca(2+) content in cells expressing mutated PS2, compared to controls. PMID:27598166

  19. 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.

  20. [Cell-ELA-based determination of binding affinity of DNA aptamer against U87-EGFRvIII cell].

    Science.gov (United States)

    Tan, Yan; Liang, Huiyu; Wu, Xidong; Gao, Yubo; Zhang, Xingmei

    2013-05-01

    A15, a DNA aptamer with binding specificity for U87 glioma cells stably overexpressing the epidermal growth factor receptor variant III (U87-EGFRvIII), was generated by cell systematic evolution of ligands by exponential enrichment (cell-SELEX) using a random nucleotide library. Subsequently, we established a cell enzyme-linked assay (cell-ELA) to detect the affinity of A15 compared to an EGFR antibody. We used A15 as a detection probe and cultured U87-EGFRvIII cells as targets. Our data indicate that the equilibrium dissociation constants (K(d)) for A15 were below 100 nmol/L and had similar affinity compared to an EGFR antibody for U87-EGFRvIII. We demonstrated that the cell-ELA was a useful method to determine the equilibrium dissociation constants (K(d)) of aptamers generated by cell-SELEX.

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. Induction and inhibition of oocyte maturation by EDCs in zebrafish

    Directory of Open Access Journals (Sweden)

    Tokumoto Mika

    2005-12-01

    Full Text Available Abstract Background Oocyte maturation in lower vertebrates is triggered by maturation-inducing hormone (MIH, which acts on unidentified receptors on the oocyte surface and induces the activation of maturation-promoting factor (MPF in the oocyte cytoplasm. We previously described the induction of oocyte maturation in fish by an endocrine-disrupting chemical (EDC, diethylstilbestrol (DES, a nonsteroidal estrogen. Methods In this study, stimulatory and inhibitory effects of EDCs and natural steroids on oocyte maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce maturation. Results Among agents tested, tamoxifen (TAM and its metabolite 4-hydroxytamoxifen (4-OHT showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP had a potent inhibitory effect on MIH-induced oocyte maturation. PCP inhibited not only MIH-induced maturation but also DES- and TAM-induced maturation. Methoxychlor also inhibited maturation when oocytes were pre-treated with this agent. Conclusion These results suggest that EDCs act as agonists or antagonists in the induction of oocyte maturation in fish.

  6. 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,

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Student Engagement and Neoliberalism: Mapping an Elective Affinity

    Science.gov (United States)

    Zepke, Nick

    2015-01-01

    The purpose of this article is to argue that student engagement, an important area for research about learning and teaching in formal higher education, has an elective affinity with neoliberalism, a hegemonic ideology in many countries of the developed world. The paper first surveys an extensive research literature examining student engagement and…

  12. Several Affinity Tags Commonly Used in Chromatographic Purification

    Directory of Open Access Journals (Sweden)

    Xinyu Zhao

    2013-01-01

    Full Text Available 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-transferase (GST, maltose-binding protein (MBP, S-tag, HA tag, and c-Myc tag. In some cases, a large-size affinity tag, such as GST or MBP, can significantly impact on the structure and biological activity of the fusion partner protein. So it is usually necessary to excise the tag by protease. The most commonly used endopeptidases are enterokinase, factor Xa, thrombin, tobacco etch virus, and human rhinovirus 3C protease. The proteolysis features of these proteases are described in order to provide a general guidance on the proteolytic removal of the affinity tags.

  13. Smooth surfaces from bilinear patches: Discrete affine minimal surfaces

    KAUST Repository

    Käferböck, Florian

    2013-06-01

    Motivated by applications in freeform architecture, we study surfaces which are composed of smoothly joined bilinear patches. These surfaces turn out to be discrete versions of negatively curved affine minimal surfaces and share many properties with their classical smooth counterparts. We present computational design approaches and study special cases which should be interesting for the architectural application. 2013 Elsevier B.V.

  14. General $L\\sb p$ affine isoperimetric inequalities

    OpenAIRE

    Haberl, Christoph; Schuster, Franz E.

    2009-01-01

    Sharp $L\\sb p$ affine isoperimetric inequalities are established for the entire class of $L\\sb p$ projection bodies and the entire class of $L\\sb p$ centroid bodies. These new inequalities strengthen the $L\\sb p$ Petty projection and the $L\\sb p$ Busemann–Petty centroid inequality.

  15. PP-waves with torsion and metric-affine gravity

    OpenAIRE

    Pasic, Vedad; Vassiliev, Dmitri

    2005-01-01

    A classical pp-wave is a 4-dimensional Lorentzian spacetime which admits a nonvanishing parallel spinor field; here the connection is assumed to be Levi-Civita. We generalise this definition to metric compatible spacetimes with torsion and describe basic properties of such spacetimes. We use our generalised pp-waves for constructing new explicit vacuum solutions of quadratic metric-affine gravity.

  16. Affinity purification of polysaccharide degrading enzymes with crosslinked substrates.

    NARCIS (Netherlands)

    Rozie, H.J.

    1992-01-01

    The aim of this work was to find economically favourable, affinity based, purification methods for several polysaccharide splitting bulk enzymes. The framework in which this study is done is described in Chapter 1.Chapter 2 describes the adsorption of endo-polygalacturonase (endoPG) from a commercia

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

    CERN Document Server

    Chou, Ching-Yi; Soo, Chopin

    2013-01-01

    Using the affine group formalism, we perform a nonperturbative quantization leading to the construction of elements of a physical Hilbert space for full, Lorentzian quantum gravity coupled to the Standard Model in four spacetime dimensions. This paper constitutes a first step toward understanding the phenomenology of quantum gravitational effects stemming from a consistent treatment of minimal couplings to matter.

  18. Self-Affine Sets with Positive Lebesgue Measure

    NARCIS (Netherlands)

    Dajani, Karma; Jiang, Kan; Kempton, Tom

    2014-01-01

    Using techniques introduced by C. G ̈unt ̈urk, we prove that the attractors of a family of overlapping self-affine iterated function systems contain a neighbourhood of zero for all parameters in a certain range. This corresponds to giving conditions under which a single sequence may serve as a ‘simu

  19. An invariant interest point detector under image affine transformation

    Institute of Scientific and Technical Information of China (English)

    林睿; 黄海波; 孙荣川; 孙立宁

    2015-01-01

    For vision-based mobile robot navigation, images of the same scene may undergo a general affine transformation in the case of significant viewpoint changes. So, a novel method for detecting affine invariant interest points is proposed to obtain the invariant local features, which is coined polynomial local orientation tensor (PLOT). The new detector is based on image local orientation tensor that is constructed from the polynomial expansion of image signal. Firstly, the properties of local orientation tensor of PLOT are analyzed, and a suitable tuning parameter of local orientation tensor is chosen so as to extract invariant features. The initial interest points are detected by local maxima search for the smaller eigenvalues of the orientation tensor. Then, an iterative procedure is used to allow the initial interest points to converge to affine invariant interest points and regions. The performances of this detector are evaluated on the repeatability criteria and recall versus 1-precision graphs, and then are compared with other existing approaches. Experimental results for PLOT show strong performance under affine transformation in the real-world conditions.

  20. Canonical bases and affine Hecke algebras of type B

    CERN Document Server

    Varagnolo, Michela

    2009-01-01

    We prove a series of conjectures of Enomoto and Kashiwara on canonical bases and branching rules of affine Hecke algebras of type B. The main ingredient of the proof is a new graded Ext-algebra associated with quiver with involutions that we compute explicitly.