The dynamics of metric-affine gravity

International Nuclear Information System (INIS)

Vitagliano, Vincenzo; Sotiriou, Thomas P.; Liberati, Stefano

2011-01-01

Highlights: → The role and the dynamics of the connection in metric-affine theories is explored. → The most general second order action does not lead to a dynamical connection. → Including higher order invariants excites new degrees of freedom in the connection. → f(R) actions are also discussed and shown to be a non- representative class. - Abstract: Metric-affine theories of gravity provide an interesting alternative to general relativity: in such an approach, the metric and the affine (not necessarily symmetric) connection are independent quantities. Furthermore, the action should include covariant derivatives of the matter fields, with the covariant derivative naturally defined using the independent connection. As a result, in metric-affine theories a direct coupling involving matter and connection is also present. The role and the dynamics of the connection in such theories is explored. We employ power counting in order to construct the action and search for the minimal requirements it should satisfy for the connection to be dynamical. We find that for the most general action containing lower order invariants of the curvature and the torsion the independent connection does not carry any dynamics. It actually reduces to the role of an auxiliary field and can be completely eliminated algebraically in favour of the metric and the matter field, introducing extra interactions with respect to general relativity. However, we also show that including higher order terms in the action radically changes this picture and excites new degrees of freedom in the connection, making it (or parts of it) dynamical. Constructing actions that constitute exceptions to this rule requires significant fine tuned and/or extra a priori constraints on the connection. We also consider f(R) actions as a particular example in order to show that they constitute a distinct class of metric-affine theories with special properties, and as such they cannot be used as representative toy

Molecular electron affinities

International Nuclear Information System (INIS)

Fukuda, E.K.

1983-01-01

Molecular electron affinities have historically been difficult quantities to measure accurately. These difficulties arise from differences in structure between the ion and neutral as well as the existence of excited negative ion states. To circumvent these problems, relative electron affinities were determined in this dissertation by studying equilibrium electron transfer reactions using a pulsed ion cyclotron resonance (ICR) spectrometer. Direct measurement of ion and neutral concentrations for reactions of the general type, A - + B = B - + A, allow calculation of the equilibrium constant and, therefore, the free energy change. The free energy difference is related to the difference in electron affinities between A and B. A relative electron affinity scale covering a range of about 45 kcal/mol was constructed with various substituted p-benzoquinones, nitrobenzenes, anhydrides, and benzophenones. To assign absolute electron affinities, various species with accurately known electron affinities are tied to the scale via ion-cyclotron double resonance bracketing techniques. After the relative scale is anchored to these species with well-known electron affinities, the scale is then used as a check on other electron affinity values as well as generating new electron affinity values. Many discrepancies were found between the electron affinities measured using the ICR technique and previous literature determinations

Realization of Robertson-Walker spacetimes as affine hypersurfaces

International Nuclear Information System (INIS)

Chen Bangyen

2007-01-01

Due to the growing interest in embeddings of spacetimes in higher dimensional spaces, we consider a special type of embedding. We prove that Robertson-Walker spacetimes can be embedded as centroaffine hypersurfaces and graph hypersurfaces in some affine spaces in such a way that the induced relative metrics are exactly the Lorentzian metrics on the Robertson-Walker spacetimes. Such realizations allow us to view Robertson-Walker spacetimes and their submanifolds as affine submanifolds in a natural way. Consequently, our realizations make it possible to apply the tools of affine differential geometry to study Robertson-Walker spacetimes and their submanifolds

USING MICROSCALE THERMOPHORESIS TO EASILY MEASURE BINDING AFFINITY

Directory of Open Access Journals (Sweden)

Dennis Breitsprecher*

2018-03-01

Full Text Available While it’s very common for biologists and chemists to test whether or not two molecules interact with each other, it’s much more useful to gather information on the nature of that interaction. How strong is it? How long will it last? What does that mean for its biological function? One way to answer these questions is to study affinity. Binding affinity is defined as the strength of the binding interaction between a single biomolecule to its binding partner, or ligand, and it can be quantifiably measured, providing information on whether or not molecules are interacting, as well as assigning a value to the affinity. When measuring binding affinity, there are several parameters to look at, but the dissociation constant (Kd, which defines the likelihood that an interaction between two molecules will break, is a very common measurement. The smaller the dissociation constant, the more tightly bound the ligand is, and the higher the affinity is between the two molecules.

The utility of affine variables and affine coherent states

International Nuclear Information System (INIS)

Klauder, John R

2012-01-01

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 appropriate. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Coherent states: mathematical and physical aspects’. (review)

Higher spins and Yangian symmetries

Energy Technology Data Exchange (ETDEWEB)

Gaberdiel, Matthias R. [Institut für Theoretische Physik, ETH Zurich, CH-8093 Zurich (Switzerland); Gopakumar, Rajesh [International Centre for Theoretical Sciences-TIFR, Survey No. 151, Shivakote, Hesaraghatta Hobli, Bengaluru North 560 089 (India); Li, Wei [CAS Key Laboratory of Theoretical Physics,Institute of Theoretical Physics, Chinese Academy of Sciences,100190 Beijing (China); Peng, Cheng [Department of Physics, Brown University, 182 Hope Street, Providence, RI 02912 (United States)

2017-04-26

The relation between the bosonic higher spin W{sub ∞}[λ] algebra, the affine Yangian of gl{sub 1}, and the SH{sup c} algebra is established in detail. For generic λ we find explicit expressions for the low-lying W{sub ∞}[λ] modes in terms of the affine Yangian generators, and deduce from this the precise identification between λ and the parameters of the affine Yangian. Furthermore, for the free field cases corresponding to λ=0 and λ=1 we give closed-form expressions for the affine Yangian generators in terms of the free fields. Interestingly, the relation between the W{sub ∞} modes and those of the affine Yangian is a non-local one, in general. We also establish the explicit dictionary between the affine Yangian and the SH{sup c} generators. Given that Yangian algebras are the hallmark of integrability, these identifications should pave the way towards uncovering the relation between the integrable and the higher spin symmetries.

Affinity Crystallography: A New Approach to Extracting High-Affinity Enzyme Inhibitors from Natural Extracts.

Science.gov (United States)

Aguda, Adeleke H; Lavallee, Vincent; Cheng, Ping; Bott, Tina M; Meimetis, Labros G; Law, Simon; Nguyen, Nham T; Williams, David E; Kaleta, Jadwiga; Villanueva, Ivan; Davies, Julian; Andersen, Raymond J; Brayer, Gary D; Brömme, Dieter

2016-08-26

Natural products are an important source of novel drug scaffolds. The highly variable and unpredictable timelines associated with isolating novel compounds and elucidating their structures have led to the demise of exploring natural product extract libraries in drug discovery programs. Here we introduce affinity crystallography as a new methodology that significantly shortens the time of the hit to active structure cycle in bioactive natural product discovery research. This affinity crystallography approach is illustrated by using semipure fractions of an actinomycetes culture extract to isolate and identify a cathepsin K inhibitor and to compare the outcome with the traditional assay-guided purification/structural analysis approach. The traditional approach resulted in the identification of the known inhibitor antipain (1) and its new but lower potency dehydration product 2, while the affinity crystallography approach led to the identification of a new high-affinity inhibitor named lichostatinal (3). The structure and potency of lichostatinal (3) was verified by total synthesis and kinetic characterization. To the best of our knowledge, this is the first example of isolating and characterizing a potent enzyme inhibitor from a partially purified crude natural product extract using a protein crystallographic approach.

Report: Affinity Chromatography.

Science.gov (United States)

Walters, Rodney R.

1985-01-01

Supports, affinity ligands, immobilization, elution methods, and a number of applications are among the topics considered in this discussion of affinity chromatography. An outline of the basic principles of affinity chromatography is included. (JN)

14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity.

Science.gov (United States)

Zádor, Ferenc; Balogh, Mihály; Váradi, András; Zádori, Zoltán S; Király, Kornél; Szűcs, Edina; Varga, Bence; Lázár, Bernadette; Hosztafi, Sándor; Riba, Pál; Benyhe, Sándor; Fürst, Susanna; Al-Khrasani, Mahmoud

2017-11-05

14-O-methyl (14-O-Me) group in morphine-6-O-sulfate (M6SU) or oxymorphone has been reported to be essential for enhanced affinity, potency and antinociceptive effect of these opioids. Herein we report on the pharmacological properties (potency, affinity and efficacy) of the new compound, 14-O-methylmorphine (14-O-MeM) in in vitro. Additionally, we also investigated the antinociceptive effect of the novel compound, as well as its inhibitory action on gastrointestinal transit in in vivo. The potency and efficacy of test compound were measured by [ 35 S]GTPγS binding, isolated mouse vas deferens (MVD) and rat vas deferens (RVD) assays. The affinity of 14-O-MeM for opioid receptors was assessed by radioligand binding and MVD assays. The antinociceptive and gastrointestinal effects of the novel compound were evaluated in the rat tail-flick test and charcoal meal test, respectively. Morphine, DAMGO, Ile 5,6 deltorphin II, deltorphin II and U-69593 were used as reference compounds. 14-O-MeM showed higher efficacy (E max ) and potency (EC 50 ) than morphine in MVD, RVD or [ 35 S]GTPγS binding. In addition, 14-O-MeM compared to morphine showed higher affinity for μ-opioid receptor (MOR). In vivo, in rat tail-flick test 14-O-MeM proved to be stronger antinociceptive agent than morphine after peripheral or central administration. Additionally, both compounds inhibited the gastrointestinal peristalsis. However, when the antinociceptive and antitransit doses for each test compound are compared, 14-O-MeM proved to have slightly more favorable pharmacological profile. Our results affirm that 14-O-MeM, an opioid of high efficacy and affinity for MOR can be considered as a novel analgesic agent of potential clinical value. Copyright © 2017 Elsevier B.V. All rights reserved.

Sperm cell purification from mock forensic swabs using SOMAmer™ affinity reagents.

Science.gov (United States)

Katilius, Evaldas; Carmel, Andrew B; Koss, Heidi; O'Connell, Dan; Smith, Breanna C; Sanders, Glenn M; LaBerge, Greggory S

2018-03-27

We have demonstrated a proof of concept with affinity-based purification of sperm cells from mock forensic samples using SOMAmer™ reagents, DNA-based affinity reagents developed by SomaLogic, Inc. SOMAmer reagents were selected in vitro using whole-cell SELEX to bind specifically with intact, detergent-treated sperm cells. Successful separation of sperm from epithelial cells and their debris was demonstrated using buccal swabs with added semen. Primarily male DNA profiles were generated from sperm cells eluted from the types of cotton swabs typically used for rape kit evidence collection. The quality of sperm DNA isolated from samples purified using SOMAmers is comparable to existing commercially available differential extraction-based methods at higher sperm concentrations. This purification method is simple, offers relatively rapid (forensic casework. Copyright © 2018. Published by Elsevier B.V.

Hirota's solitons in the affine and the conformal affine Toda models

International Nuclear Information System (INIS)

Aratyn, H.; Constantinidis, C.P.; Ferreira, L.A.; Gomes, J.F.; Zimerman, A.H.

1993-01-01

We use Hirota's method formulated as a recursive scheme to construct a complete set of soliton solutions for the affine Toda field theory based on an arbitrary Lie algebra. Our solutions include a new class of solitons connected with two different types of degeneracies encountered in Hirota's perturbation approach. We also derive an universal mass formula for all Hirota's solutions to the affine Toda model valid for all underlying Lie groups. Embedding of the affine Toda model in the conformal affine Toda model plays a crucial role in this analysis. (orig.)

Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo.

Science.gov (United States)

Roelofs, Anke J; Stewart, Charlotte A; Sun, Shuting; Błażewska, Katarzyna M; Kashemirov, Boris A; McKenna, Charles E; Russell, R Graham G; Rogers, Michael J; Lundy, Mark W; Ebetino, Frank H; Coxon, Fraser P

2012-04-01

Bisphosphonates are widely used antiresorptive drugs that bind to calcium. It has become evident that these drugs have differing affinities for bone mineral; however, it is unclear whether such differences affect their distribution on mineral surfaces. In this study, fluorescent conjugates of risedronate, and its lower-affinity analogues deoxy-risedronate and 3-PEHPC, were used to compare the localization of compounds with differing mineral affinities in vivo. Binding to dentine in vitro confirmed differences in mineral binding between compounds, which was influenced predominantly by the characteristics of the parent compound but also by the choice of fluorescent tag. In growing rats, all compounds preferentially bound to forming endocortical as opposed to resorbing periosteal surfaces in cortical bone, 1 day after administration. At resorbing surfaces, lower-affinity compounds showed preferential binding to resorption lacunae, whereas the highest-affinity compound showed more uniform labeling. At forming surfaces, penetration into the mineralizing osteoid was found to inversely correlate with mineral affinity. These differences in distribution at resorbing and forming surfaces were not observed at quiescent surfaces. Lower-affinity compounds also showed a relatively higher degree of labeling of osteocyte lacunar walls and labeled lacunae deeper within cortical bone, indicating increased penetration of the osteocyte canalicular network. Similar differences in mineralizing surface and osteocyte network penetration between high- and low-affinity compounds were evident 7 days after administration, with fluorescent conjugates at forming surfaces buried under a new layer of bone. Fluorescent compounds were incorporated into these areas of newly formed bone, indicating that "recycling" had occurred, albeit at very low levels. Taken together, these findings indicate that the bone mineral affinity of bisphosphonates is likely to influence their distribution within the

The solutions of affine and conformal affine Toda field theory

International Nuclear Information System (INIS)

Papadopoulos, G.; Spence, B.

1994-02-01

We give new formulations of the solutions of the field equations of the affine Toda and conformal affine Toda theories on a cylinder and two-dimensional Minkowski space-time. These solutions are parameterised in terms of initial data and the resulting covariant phase spaces are diffeomorphic to the Hamiltonian ones. We derive the fundamental Poisson brackets of the parameters of the solutions and give the general static solutions for the affine theory. (authors). 10 refs

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.

Lectin affinity electrophoresis.

Science.gov (United States)

Kobayashi, Yuka

2014-01-01

An interaction or a binding event typically changes the electrophoretic properties of a molecule. Affinity electrophoresis methods detect changes in the electrophoretic pattern of molecules (mainly macromolecules) that occur as a result of biospecific interactions or complex formation. Lectin affinity electrophoresis is a very effective method for the detection and analysis of trace amounts of glycobiological substances. It is particularly useful for isolating and separating the glycoisomers of target molecules. Here, we describe a sensitive technique for the detection of glycoproteins separated by agarose gel-lectin affinity electrophoresis that uses antibody-affinity blotting. The technique is tested using α-fetoprotein with lectin (Lens culinaris agglutinin and Phaseolus vulgaris agglutinin)-agarose gels.

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...

Affinity between information retrieval system and search topic

International Nuclear Information System (INIS)

Ebinuma, Yukio

1979-01-01

Ten search profiles are tested on the INIS system at the Japan Atomic Energy Research Institute. The results are plotted on recall-precision chart ranging from 100% recall to 100% precision. The curves are not purely systems-dependent nor search-dependent, and are determined substantially by the ''affinity'' between the system and the search topic. The curves are named ''Affinity curves of search topics with information retrieval systems'', and hence retrieval affinity factors are derived. They are obtained not only for individual search topics but also for averages in the system. By such a quantitative examination, the difference of affinity among search topics in a given system, that of the same search topic among various systems, and that of systems to the same group of search topics can be compared reasonably. (author)

Lp-dual affine surface area

Science.gov (United States)

Wei, Wang; Binwu, He

2008-12-01

According to the notion of Lp-affine surface area by Lutwak, in this paper, we introduce the concept of Lp-dual affine surface area. Further, we establish the affine isoperimetric inequality and the Blaschke-Santaló inequality for Lp-dual affine surface area. Besides, the dual Brunn-Minkowski inequality for Lp-dual affine surface area is presented.

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.

Myoglobin oxygen affinity in aquatic and terrestrial birds and mammals.

Science.gov (United States)

Wright, Traver J; Davis, Randall W

2015-07-01

Myoglobin (Mb) is an oxygen binding protein found in vertebrate skeletal muscle, where it facilitates intracellular transport and storage of oxygen. This protein has evolved to suit unique physiological needs in the muscle of diving vertebrates that express Mb at much greater concentrations than their terrestrial counterparts. In this study, we characterized Mb oxygen affinity (P50) from 25 species of aquatic and terrestrial birds and mammals. Among diving species, we tested for correlations between Mb P50 and routine dive duration. Across all species examined, Mb P50 ranged from 2.40 to 4.85 mmHg. The mean P50 of Mb from terrestrial ungulates was 3.72±0.15 mmHg (range 3.70-3.74 mmHg). The P50 of cetaceans was similar to terrestrial ungulates ranging from 3.54 to 3.82 mmHg, with the exception of the melon-headed whale, which had a significantly higher P50 of 4.85 mmHg. Among pinnipeds, the P50 ranged from 3.23 to 3.81 mmHg and showed a trend for higher oxygen affinity in species with longer dive durations. Among diving birds, the P50 ranged from 2.40 to 3.36 mmHg and also showed a trend of higher affinities in species with longer dive durations. In pinnipeds and birds, low Mb P50 was associated with species whose muscles are metabolically active under hypoxic conditions associated with aerobic dives. Given the broad range of potential globin oxygen affinities, Mb P50 from diverse vertebrate species appears constrained within a relatively narrow range. High Mb oxygen affinity within this range may be adaptive for some vertebrates that make prolonged dives. © 2015. Published by The Company of Biologists Ltd.

Continuous affine processes

DEFF Research Database (Denmark)

Buchardt, Kristian

2016-01-01

Affine processes possess the property that expectations of exponential affine transformations are given by a set of Riccati differential equations, which is the main feature of this popular class of processes. In this paper we generalise these results for expectations of more general transformati...

Protein-phosphotyrosine proteome profiling by superbinder-SH2 domain affinity purification mass spectrometry, sSH2-AP-MS.

Science.gov (United States)

Tong, Jiefei; Cao, Biyin; Martyn, Gregory D; Krieger, Jonathan R; Taylor, Paul; Yates, Bradley; Sidhu, Sachdev S; Li, Shawn S C; Mao, Xinliang; Moran, Michael F

2017-03-01

Recently, "superbinder" SH2 domain variants with three amino acid substitutions (sSH2) were reported to have 100-fold or greater affinity for protein-phosphotyrosine (pY) than natural SH2 domains. Here we report a protocol in which His-tagged Src sSH2 efficiently captures pY-peptides from protease-digested HeLa cell total protein extracts. Affinity purification of pY-peptides by this method shows little bias for pY-proximal amino acid sequences, comparable to that achieved by using antibodies to pY, but with equal or higher yield. Superbinder-SH2 affinity purification mass spectrometry (sSH2-AP-MS) therefore provides an efficient and economical approach for unbiased pY-directed phospho-proteome profiling without the use of antibodies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Affinity in electrophoresis.

Science.gov (United States)

Heegaard, Niels H H

2009-06-01

The journal Electrophoresis has greatly influenced my approaches to biomolecular affinity studies. The methods that I have chosen as my main tools to study interacting biomolecules--native gel and later capillary zone electrophoresis--have been the topic of numerous articles in Electrophoresis. Below, the role of the journal in the development and dissemination of these techniques and applications reviewed. Many exhaustive reviews on affinity electrophoresis and affinity CE have been published in the last few years and are not in any way replaced by the present deliberations that are focused on papers published by the journal.

The metric-affine gravitational theory as the gauge theory of the affine group

International Nuclear Information System (INIS)

Lord, E.A.

1978-01-01

The metric-affine gravitational theory is shown to be the gauge theory of the affine group, or equivalently, the gauge theory of the group GL(4,R) of tetrad deformations in a space-time with a locally Minkowskian metric. The identities of the metric-affine theory, and the relationship between them and those of general relativity and Sciama-Kibble theory, are derived. (Auth.)

An improved affine projection algorithm for active noise cancellation

Science.gov (United States)

Zhang, Congyan; Wang, Mingjiang; Han, Yufei; Sun, Yunzhuo

2017-08-01

Affine projection algorithm is a signal reuse algorithm, and it has a good convergence rate compared to other traditional adaptive filtering algorithm. There are two factors that affect the performance of the algorithm, which are step factor and the projection length. In the paper, we propose a new variable step size affine projection algorithm (VSS-APA). It dynamically changes the step size according to certain rules, so that it can get smaller steady-state error and faster convergence speed. Simulation results can prove that its performance is superior to the traditional affine projection algorithm and in the active noise control (ANC) applications, the new algorithm can get very good results.

Three Decades of Implementation Research in Higher Education: Limitations and Prospects of Theory Development

Science.gov (United States)

Kohoutek, Jan

2013-01-01

The article adopts a comparative approach to review three periods of theory development in research into higher education policy implementation. Given the conceptual affinity between Cerych and Sabatier's 1986 seminal study into higher education policy implementation and public policy implementation theory, the field of public policy is chosen for…

A Generalized Affine Isoperimetric Inequality

OpenAIRE

Chen, Wenxiong; Howard, Ralph; Lutwak, Erwin; Yang, Deane; Zhang, Gaoyong

2004-01-01

A purely analytic proof is given for an inequality that has as a direct consequence the two most important affine isoperimetric inequalities of plane convex geometry: The Blaschke-Santalo inequality and the affine isoperimetric inequality of affine differential geometry.

Binding Affinity of a Highly Sensitive Au/Ag/Au/Chitosan-Graphene Oxide Sensor Based on Direct Detection of Pb2+ and Hg2+ Ions

Directory of Open Access Journals (Sweden)

Nur Hasiba Kamaruddin

2017-10-01

Full Text Available The study of binding affinity is essential in surface plasmon resonance (SPR sensing because it allows researchers to quantify the affinity between the analyte and immobilised ligands of an SPR sensor. In this study, we demonstrate the derivation of the binding affinity constant, K, for Pb2+ and Hg2+ ions according to their SPR response using a gold/silver/gold/chitosan–graphene oxide (Au/Ag/Au/CS–GO sensor for the concentration range of 0.1–5 ppm. The higher affinity of Pb2+ to binding with the CS–GO sensor explains the outstanding sensitivity of 2.05 °ppm−1 against 1.66 °ppm−1 of Hg2+. The maximum signal-to-noise ratio (SNR upon detection of Pb2+ is 1.53, and exceeds the suggested logical criterion of an SNR. The Au/Ag/Au/CS–GO SPR sensor also exhibits excellent repeatability in Pb2+ due to the strong bond between its functional groups and this cation. The adsorption data of Pb2+ and Hg2+ on the CS–GO sensor fits well with the Langmuir isotherm model where the affinity constant, K, of Pb2+ and Hg2+ ions is computed. The affinity of Pb2+ ions to the Au/Ag/Au/CS–GO sensor is significantly higher than that of Hg2+ based on the value of K, 7 × 105 M−1 and 4 × 105 M−1, respectively. The higher shift in SPR angles due to Pb2+ and Hg2+ compared to Cr3+, Cu2+ and Zn2+ ions also reveals the greater affinity of the CS–GO SPR sensor to them, thus supporting the rationale for obtaining K for these two heavy metals. This study provides a better understanding on the sensing performance of such sensors in detecting heavy metal ions.

Lp-mixed affine surface area

Science.gov (United States)

Wang, Weidong; Leng, Gangsong

2007-11-01

According to the three notions of mixed affine surface area, Lp-affine surface area and Lp-mixed affine surface area proposed by Lutwak, in this article, we give the concept of ith Lp-mixed affine surface area such that the first and second notions of Lutwak are its special cases. Further, some Lutwak's results are extended associated with this concept. Besides, applying this concept, we establish an inequality for the volumes and dual quermassintegrals of a class of star bodies.

Supramolecular Affinity Chromatography for Methylation-Targeted Proteomics.

Science.gov (United States)

Garnett, Graham A E; Starke, Melissa J; Shaurya, Alok; Li, Janessa; Hof, Fraser

2016-04-05

Proteome-wide studies of post-translationally methylated species using mass spectrometry are complicated by high sample diversity, competition for ionization among peptides, and mass redundancies. Antibody-based enrichment has powered methylation proteomics until now, but the reliability, pan-specificity, polyclonal nature, and stability of the available pan-specific antibodies are problematic and do not provide a standard, reliable platform for investigators. We have invented an anionic supramolecular host that can form host-guest complexes selectively with methyllysine-containing peptides and used it to create a methylysine-affinity column. The column resolves peptides on the basis of methylation-a feat impossible with a comparable commercial cation-exchange column. A proteolyzed nuclear extract was separated on the methyl-affinity column prior to standard proteomics analysis. This experiment demonstrates that such chemical methyl-affinity columns are capable of enriching and improving the analysis of methyllysine residues from complex protein mixtures. We discuss the importance of this advance in the context of biomolecule-driven enrichment methods.

Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

Directory of Open Access Journals (Sweden)

Mora Xavier

2007-05-01

Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

Mapping Affinities in Academic Organizations

Directory of Open Access Journals (Sweden)

Dario Rodighiero

2018-02-01

Full Text Available Scholarly affinities are one of the most fundamental hidden dynamics that drive scientific development. Some affinities are actual, and consequently can be measured through classical academic metrics such as co-authoring. Other affinities are potential, and therefore do not leave visible traces in information systems; for instance, some peers may share interests without actually knowing it. This article illustrates the development of a map of affinities for academic collectives, designed to be relevant to three audiences: the management, the scholars themselves, and the external public. Our case study involves the School of Architecture, Civil and Environmental Engineering of EPFL, hereinafter ENAC. The school consists of around 1,000 scholars, 70 laboratories, and 3 institutes. The actual affinities are modeled using the data available from the information systems reporting publications, teaching, and advising scholars, whereas the potential affinities are addressed through text mining of the publications. The major challenge for designing such a map is to represent the multi-dimensionality and multi-scale nature of the information. The affinities are not limited to the computation of heterogeneous sources of information; they also apply at different scales. The map, thus, shows local affinities inside a given laboratory, as well as global affinities among laboratories. This article presents a graphical grammar to represent affinities. Its effectiveness is illustrated by two actualizations of the design proposal: an interactive online system in which the map can be parameterized, and a large-scale carpet of 250 square meters. In both cases, we discuss how the materiality influences the representation of data, in particular the way key questions could be appropriately addressed considering the three target audiences: the insights gained by the management and their consequences in terms of governance, the understanding of the scholars’ own

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…

Non-contact adhesion to self-affine surfaces: A theoretical model

Energy Technology Data Exchange (ETDEWEB)

Makeev, Maxim A., E-mail: makeev@umich.edu

2013-11-22

Strength of adhesion between materials is known to be strongly influenced by interface irregularities. In this work, I devise a perturbative approach to describe the effect of self-affine roughness on non-contact adhesive interactions. The hierarchy of the obtained analytical solutions is the following. First, analytical formulae are deduced to describe roughness corrections to the van der Waals interaction energies between a hemi-space adherend, bounded by a self-affine surface, and a point-like adherent. Second, the problem of two hemi-spaces, one of which has a planar surface, and the other is bounded by a self-affine surface, is solved analytically. In the latter case, a numerical analysis is performed to delineate the behavior of the roughness corrections as a function of the parameters, characterizing self-affine fractal surface roughness. The problem of two hemi-spaces, both bounded by self-affine fractal surfaces, is also addressed in this work. The model's predictions are compared with previously reported theoretical results and available experimental data.

Synthesis, modelling, and mu-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicycl.

Science.gov (United States)

Pinna, G A; Murineddu, G; Curzu, M M; Villa, S; Vianello, P; Borea, P A; Gessi, S; Toma, L; Colombo, D; Cignarella, G

2000-08-01

A series of N-3-arylpropenyl-N-9-propionyl-3,9-diazabicyclo[3.3.1]nonanes (1a-g) and of reverted N-3-propionyl-N-9-arylpropenyl isomers (2a-g), as homologues of the previously reported analgesic 3,8-diazabicyclo[3.2.1]octanes (I-II), were synthesized and evaluated for the binding affinity towards opioid receptor subtypes mu, delta and kappa. Compounds 1a-g and 2a-g exhibited a strong selective mu-affinity with Ki values in the nanomolar range, which favourably compared with those of I and II. In addition, contrary to the trend observed for DBO-I, II, the mu-affinity of series 2 is markedly higher than that of the isomeric series 1. This aspect was discussed on the basis of the conformational studies performed on DBN which allowed hypotheses on the mode of interaction of these compounds with the mu receptor.

Comparatives Korean and Mongolian Achievement In Higher Education

OpenAIRE

Uranchimeg Julia Agvaantseren; Park Sae Hoon

2013-01-01

The purpose of this paper is to introduce the transition of Korean higher education reform and to study of Korean and Mongolian experience and achievement in contemporary higher education. And also paper provides a description of the higher education in Mongolia in an effort to identify important financial issues and concern while comparing with Korean high education experience and tries to attract attention of policy makers for better alternative...

Preparation of Affinity Column Based on Zr4+ Ion for Phosphoproteins Isolation

International Nuclear Information System (INIS)

Lee, Seon Mi; Bae, In Ae; Park, Jung Hyen; Kim, Tae Dong; Choi, Seong Ho

2009-01-01

This paper has described about preparation of Zr 4+ affinity column based on the poly(styreneco- glycidyl methacrylate) prepared by emulsion polymerization of styrene and glycidyl methacrylate in order to isolate phosphopeptide. The Zr 4+ ions were introduced after the phophonation of an epoxy group on polymeric microspheres. The successful preparation of Zr 4+ -immobilized polymeric microsphere stationary phase was confirmed through Fourier transform infrared spectra, optical microscopy, scanning electron microscopy, X-ray photoelectron spectra and inductively coupled plasma-atomic emission spectrometer. The separation efficiency for Zr 4+ affinity column prepared by slurry packing was tested to phosphonated casein and dephosphonated casein. The resolution time (min) of the phosphonated casein was higher than that of dephosphated casein for Zr 4+ affinity polymeric microsphere by liquid chromatography. This Zr 4+ affinity column can be used for isolation of phosphonated casein from casein using liquid chromatography

Importance of Hypervariable Region 2 for Stability and Affinity of a Shark Single-Domain Antibody Specific for Ebola Virus Nucleoprotein.

Directory of Open Access Journals (Sweden)

George P Anderson

Full Text Available Single-domain antibodies derived from the unique New Antigen Receptor found in sharks have numerous potential applications, ranging from diagnostic reagents to therapeutics. Shark-derived single-domain antibodies possess the same characteristic ability to refold after heat denaturation found in single-domain antibodies derived from camelid heavy-chain-only antibodies. Recently, two shark derived single-domain antibodies specific for the nucleoprotein of Ebola virus were described. Our evaluation confirmed their high affinity for the nucleoprotein, but found their melting temperatures to be low relative to most single-domain antibodies. Our first approach towards improving their stability was grafting antigen-binding regions (complementarity determining regions of one of these single-domain antibodies onto a high melting temperature shark single-domain antibody. This resulted in two variants: one that displayed excellent affinity with a low melting temperature, while the other had poor affinity but a higher melting temperature. These new proteins, however, differed in only 3 amino acids within the complementarity determining region 2 sequence. In shark single-domain antibodies, the complementarity determining region 2 is often referred to as hypervariable region 2, as this segment of the antibody domain is truncated compared to the sequence in camelid single-domain antibodies and conventional heavy chain variable domains. To elucidate which of the three amino acids or combinations thereof were responsible for the affinity and stability we made the 6 double and single point mutants that covered the intermediates between these two clones. We found a single amino acid change that achieved a 10°C higher melting temperature while maintaining sub nM affinity. This research gives insights into the impact of the shark sdAb hypervariable 2 region on both stability and affinity.

Affine field theories

International Nuclear Information System (INIS)

Cadavid, A.C.

1989-01-01

The author constructs a non-Abelian field theory by gauging a Kac-Moody algebra, obtaining an infinite tower of interacting vector fields and associated ghosts, that obey slightly modified Feynman rules. She discusses the spontaneous symmetry breaking of such theory via the Higgs mechanism. If the Higgs particle lies in the Cartan subalgebra of the Kac-Moody algebra, the previously massless vectors acquire a mass spectrum that is linear in the Kac-Moody index and has additional fine structure depending on the associated Lie algebra. She proceeds to show that there is no obstacle in implementing the affine extension of supersymmetric Yang-Mills theories. The result is valid in four, six and ten space-time dimensions. Then the affine extension of supergravity is investigated. She discusses only the loop algebra since the affine extension of the super-Poincare algebra appears inconsistent. The construction of the affine supergravity theory is carried out by the group manifold method and leads to an action describing infinite towers of spin 2 and spin 3/2 fields that interact subject to the symmetries of the loop algebra. The equations of motion satisfy the usual consistency check. Finally, she postulates a theory in which both the vector and scalar fields lie in the loop algebra of SO(3). This theory has an expanded soliton sector, and corresponding to the original 't Hooft-Polyakov solitonic solutions she now finds an infinite family of exact, special solutions of the new equations. She also proposes a perturbation method for obtaining an arbitrary solution of those equations for each level of the affine index

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

OpenAIRE

Stewart, Rachel C.; Bansal, Prashant N.; Entezari, Vahid; Lusic, Hrvoje; Nazarian, Rosalynn M.; Snyder, Brian D.; Grinstaff, Mark W.

2013-01-01

The high affinity of a cationic iodinated contrast agent for cartilage provides better tissue visualization, easier segmentation, higher contrast-to-noise ratios, and longer usable imaging windows and requires a lower dose of injected contrast agent compared with an anionic contrast agent.

Specificity and affinity quantification of protein-protein interactions.

Science.gov (United States)

Yan, Zhiqiang; Guo, Liyong; Hu, Liang; Wang, Jin

2013-05-01

Most biological processes are mediated by the protein-protein interactions. Determination of the protein-protein structures and insight into their interactions are vital to understand the mechanisms of protein functions. Currently, compared with the isolated protein structures, only a small fraction of protein-protein structures are experimentally solved. Therefore, the computational docking methods play an increasing role in predicting the structures and interactions of protein-protein complexes. The scoring function of protein-protein interactions is the key responsible for the accuracy of the computational docking. Previous scoring functions were mostly developed by optimizing the binding affinity which determines the stability of the protein-protein complex, but they are often lack of the consideration of specificity which determines the discrimination of native protein-protein complex against competitive ones. We developed a scoring function (named as SPA-PP, specificity and affinity of the protein-protein interactions) by incorporating both the specificity and affinity into the optimization strategy. The testing results and comparisons with other scoring functions show that SPA-PP performs remarkably on both predictions of binding pose and binding affinity. Thus, SPA-PP is a promising quantification of protein-protein interactions, which can be implemented into the protein docking tools and applied for the predictions of protein-protein structure and affinity. The algorithm is implemented in C language, and the code can be downloaded from http://dl.dropbox.com/u/1865642/Optimization.cpp.

High affinity binding of [3H]cocaine to rat liver microsomes

International Nuclear Information System (INIS)

El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

1988-01-01

] 3 H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [ 3 H]cocaine binding. On the other hand, chronic administration of cocaine reduced [ 3 H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [ 3 H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [ 3 H]cocaine binding to liver with a different rank order of potency than their displacement of [ 3 H]cocaine binding to striatum. This high affinity [ 3 H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

Modifiers of hemoglobin/oxygen affinity as sensitizers of tumors to radiation

International Nuclear Information System (INIS)

Hirst, D.G.; Wood, P.J.

1987-01-01

A powerful mechanism in the control of oxygen delivery to tissues is the allosteric modification of hemoglobin. Increased or decreased release of oxygen can be achieved by altering the affinity of hemoglobin for oxygen. Several studies have shown that tumor radiosensitivity is dependent on this relationship. The authors studied affinity changes produced in two distinctly different ways. Tumor bearing mice were given isovolemic exchange blood transfusions with the blood from donor mice which had been exposed to abnormal oxygen tensions, leading to increased or slightly decreased levels of 2,3-diphosphoglycerate (2,3 DPG) in their blood. When the recipient mice were irradiated, those receiving the blood with higher 2,3 DPG levels showed greater tumor sensitivity to radiation. An alternative strategy is the use of drugs which directly alter hemoglobin/oxygen affinity. The authors studied three antihyperlipoproteinemia drugs, all of which have produced markedly reduced affinities in vivo. Preliminary data indicate that the radiosensitization produced by at least one of these compounds is less than would have been expected from the 2,3 DPG experiments

Quantifying high-affinity binding of hydrophobic ligands by isothermal titration calorimetry.

Science.gov (United States)

Krainer, Georg; Broecker, Jana; Vargas, Carolyn; Fanghänel, Jörg; Keller, Sandro

2012-12-18

A fast and reliable quantification of the binding thermodynamics of hydrophobic high-affinity ligands employing a new calorimetric competition experiment is described. Although isothermal titration calorimetry is the method of choice for a quantitative characterization of intermolecular interactions in solution, a reliable determination of a dissociation constant (K(D)) is typically limited to the range 100 μM > K(D) > 1 nM. Interactions displaying higher or lower K(D) values can be assessed indirectly, provided that a suitable competing ligand is available whose K(D) falls within the directly accessible affinity window. This established displacement assay, however, requires the high-affinity ligand to be soluble at high concentrations in aqueous buffer and, consequently, poses serious problems in the study of protein binding involving small-molecule ligands dissolved in organic solvents--a familiar case in many drug-discovery projects relying on compound libraries. The calorimetric competition assay introduced here overcomes this limitation, thus allowing for a detailed thermodynamic description of high-affinity receptor-ligand interactions involving poorly water-soluble compounds. Based on a single titration of receptor into a dilute mixture of the two competing ligands, this competition assay provides accurate and precise values for the dissociation constants and binding enthalpies of both high- and moderate-affinity ligands. We discuss the theoretical background underlying the approach, demonstrate its practical application to metal ion chelation and high-affinity protein-inhibitor interactions, and explore its potential and limitations with the aid of simulations and statistical analyses.

Binding affinities of anti-acetylcholine receptor autoantibodies in myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Bray, J.J.; Drachman, D.B.

1982-01-01

Antibodies directed against acetylcholine (ACh) receptors are present in the sera of nearly 90% of patients with myasthenia gravis (MG), and are involved in the pathogenesis of this autoimmune disease. However, the antibody titers measured by the standard radioimmunoassay correspond poorly with the clinical severity of the disease. To determine whether this disparity could be accounted for by differences in the binding affinities of anti-ACh receptor antibodies in different patients, we have measured the binding affinities of these autoantibodies in 15 sera from MG patients. The affinity constants (K/sub o/), as determined by Scatchard analysis, were all in the range of 10/sup 10/ M/sup -1/, comparable to the highest values reported in immunized animals. The affinity constants were truly representative of the population of autoantibodies detected by the radioimmunoassay, as shown by the remarkable linearity of the Scatchard plots (r/sup 2/>0.90) and the close correlation between the antibody titers determined by extrapolation of the Scatchard plots and by saturation analysis (r = 0.99; p < 0.001). There was only a 6-fold variation in affinity constants measured in this series of patients despite widely differing antibody titers and severity of the disease. Factors other than the titer and affinity of anti-ACh receptor antibodies may correlate better with the clinical manifestations of MG.

Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation.

Science.gov (United States)

Ma, Xiaoli; He, Jiawei; Yan, Jin; Wang, Qing; Li, Hui

2016-03-25

Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preparation of Affinity Column Based on Zr{sup 4+} Ion for Phosphoproteins Isolation

Energy Technology Data Exchange (ETDEWEB)

Lee, Seon Mi; Bae, In Ae; Park, Jung Hyen; Kim, Tae Dong; Choi, Seong Ho [Hannam University, Daejeon (Korea, Republic of)

2009-06-15

This paper has described about preparation of Zr{sup 4+} affinity column based on the poly(styreneco- glycidyl methacrylate) prepared by emulsion polymerization of styrene and glycidyl methacrylate in order to isolate phosphopeptide. The Zr{sup 4+} ions were introduced after the phophonation of an epoxy group on polymeric microspheres. The successful preparation of Zr{sup 4+}-immobilized polymeric microsphere stationary phase was confirmed through Fourier transform infrared spectra, optical microscopy, scanning electron microscopy, X-ray photoelectron spectra and inductively coupled plasma-atomic emission spectrometer. The separation efficiency for Zr{sup 4+} affinity column prepared by slurry packing was tested to phosphonated casein and dephosphonated casein. The resolution time (min) of the phosphonated casein was higher than that of dephosphated casein for Zr{sup 4+} affinity polymeric microsphere by liquid chromatography. This Zr{sup 4+} affinity column can be used for isolation of phosphonated casein from casein using liquid chromatography.

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.

2017 Guralp Affinity Digitizer Evaluation.

Energy Technology Data Exchange (ETDEWEB)

Merchant, Bion J.

2018-03-01

Sandia National Laboratories has tested and evaluated two Guralp Affinity digitizers. The Affinity digitizers are intended to record sensor output for seismic and infrasound monitoring applications. The purpose of this digitizer evaluation is to measure the performance characteristics in such areas as power consumption, input impedance, sensitivity, full scale, self- noise, dynamic range, system noise, response, passband, and timing. The Affinity digitizers are being evaluated for potential use in the International Monitoring System (IMS) of the Comprehensive Nuclear Test-Ban-Treaty Organization (CTBTO).

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

International Nuclear Information System (INIS)

Hu Naihong; Rosso, M.; Zhang Honglian

2006-12-01

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

Rational design of peptide affinity ligands for the purification of therapeutic enzymes.

Science.gov (United States)

Trasatti, John P; Woo, James; Ladiwala, Asif; Cramer, Steven; Karande, Pankaj

2018-04-25

Non-mAb biologics represent a growing class of therapeutics under clinical development. Although affinity chromatography is a potentially attractive approach for purification, the development of platform technologies, such as Protein A for mAbs, has been challenging due to the inherent chemical and structural diversity of these molecules. Here, we present our studies on the rapid development of peptide affinity ligands for the purification of biologics using a prototypical enzyme therapeutic in clinical use. Employing a suite of de novo rational and combinatorial design strategies we designed and screened a library of peptides on microarray platforms for their ability to bind to the target with high affinity and selectivity in cell culture fluid. Lead peptides were evaluated on resin in batch conditions and compared with a commercially available resin to evaluate their efficacy. Two lead candidates identified from microarray studies provided high binding capacity to the target while demonstrating high selectivity against culture contaminants and product variants compared to a commercial resin system. These findings provide a proof-of-concept for developing affinity peptide-based bioseparations processes for a target biologic. Peptide affinity ligand design and screening approaches presented in this work can also be easily translated to other biologics of interest. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

Role of T cell receptor affinity in the efficacy and specificity of adoptive T cell therapies

Directory of Open Access Journals (Sweden)

Jennifer D. Stone

2013-08-01

Full Text Available Over the last several years, there has been considerable progress in the treatment of cancer using gene modified adoptive T cell therapies. Two approaches have been used, one involving the introduction of a conventional alpha-beta T cell receptor (TCR against a pepMHC cancer antigen, and the second involving introduction of a chimeric antigen receptor (CAR consisting of a single-chain antibody as an Fv fragment (scFv linked to transmembrane and signaling domains. In this review, we focus on one aspect of TCR-mediated adoptive T cell therapies, the impact of the affinity of the alpha-beta TCR for the pepMHC cancer antigen on both efficacy and specificity. We discuss the advantages of higher affinity TCRs in mediating potent activity of CD4 T cells. This is balanced with the potential disadvantage of higher affinity TCRs in mediating greater self-reactivity against a wider range of structurally similar antigenic peptides, especially in synergy with the CD8 co-receptor. Both TCR affinity and target selection will influence potential safety issues. We suggest pre-clinical strategies that might be used to examine each TCR for possible on-target and off-target side effects due to self-reactivities, and to adjust TCR affinities accordingly.

Immobilizing affinity proteins to nitrocellulose: a toolbox for paper-based assay developers.

Science.gov (United States)

Holstein, Carly A; Chevalier, Aaron; Bennett, Steven; Anderson, Caitlin E; Keniston, Karen; Olsen, Cathryn; Li, Bing; Bales, Brian; Moore, David R; Fu, Elain; Baker, David; Yager, Paul

2016-02-01

To enable enhanced paper-based diagnostics with improved detection capabilities, new methods are needed to immobilize affinity reagents to porous substrates, especially for capture molecules other than IgG. To this end, we have developed and characterized three novel methods for immobilizing protein-based affinity reagents to nitrocellulose membranes. We have demonstrated these methods using recombinant affinity proteins for the influenza surface protein hemagglutinin, leveraging the customizability of these recombinant "flu binders" for the design of features for immobilization. The three approaches shown are: (1) covalent attachment of thiolated affinity protein to an epoxide-functionalized nitrocellulose membrane, (2) attachment of biotinylated affinity protein through a nitrocellulose-binding streptavidin anchor protein, and (3) fusion of affinity protein to a novel nitrocellulose-binding anchor protein for direct coupling and immobilization. We also characterized the use of direct adsorption for the flu binders, as a point of comparison and motivation for these novel methods. Finally, we demonstrated that these novel methods can provide improved performance to an influenza hemagglutinin assay, compared to a traditional antibody-based capture system. Taken together, this work advances the toolkit available for the development of next-generation paper-based diagnostics.

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

Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

International Nuclear Information System (INIS)

Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

2008-01-01

The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

Antisymmetric tensor generalizations of affine vector fields.

Science.gov (United States)

Houri, Tsuyoshi; Morisawa, Yoshiyuki; Tomoda, Kentaro

2016-02-01

Tensor generalizations of affine vector fields called symmetric and antisymmetric affine tensor fields are discussed as symmetry of spacetimes. We review the properties of the symmetric ones, which have been studied in earlier works, and investigate the properties of the antisymmetric ones, which are the main theme in this paper. It is shown that antisymmetric affine tensor fields are closely related to one-lower-rank antisymmetric tensor fields which are parallelly transported along geodesics. It is also shown that the number of linear independent rank- p antisymmetric affine tensor fields in n -dimensions is bounded by ( n + 1)!/ p !( n - p )!. We also derive the integrability conditions for antisymmetric affine tensor fields. Using the integrability conditions, we discuss the existence of antisymmetric affine tensor fields on various spacetimes.

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.

Higher Education in Greece Compared to Canada

Science.gov (United States)

Miliotis, Helen

2014-01-01

This paper compares and contrasts higher education in Canada and Greece. An overview of the systems in place is followed by an analysis centred on the triad of funding, access and quality. Similarities and differences are highlighted, and the current challenges and issues faced by both nations will be examined, especially in terms of world…

Dextran as a Generally Applicable Multivalent Scaffold for Improving Immunoglobulin-Binding Affinities of Peptide and Peptidomimetic Ligands

Science.gov (United States)

2015-01-01

Molecules able to bind the antigen-binding sites of antibodies are of interest in medicine and immunology. Since most antibodies are bivalent, higher affinity recognition can be achieved through avidity effects in which a construct containing two or more copies of the ligand engages both arms of the immunoglobulin simultaneously. This can be achieved routinely by immobilizing antibody ligands at high density on solid surfaces, such as ELISA plates, but there is surprisingly little literature on scaffolds that routinely support bivalent binding of antibody ligands in solution, particularly for the important case of human IgG antibodies. Here we show that the simple strategy of linking two antigens with a polyethylene glycol (PEG) spacer long enough to span the two arms of an antibody results in higher affinity binding in some, but not all, cases. However, we found that the creation of multimeric constructs in which several antibody ligands are displayed on a dextran polymer reliably provides much higher affinity binding than is observed with the monomer in all cases tested. Since these dextran conjugates are simple to construct, they provide a general and convenient strategy to transform modest affinity antibody ligands into high affinity probes. An additional advantage is that the antibody ligands occupy only a small number of the reactive sites on the dextran, so that molecular cargo can be attached easily, creating molecules capable of delivering this cargo to cells displaying antigen-specific receptors. PMID:25073654

Affine LIBOR Models with Multiple Curves

DEFF Research Database (Denmark)

Grbac, Zorana; Papapantoleon, Antonis; Schoenmakers, John

2015-01-01

are specified following the methodology of the affine LIBOR models and are driven by the wide and flexible class of affine processes. The affine property is preserved under forward measures, which allows us to derive Fourier pricing formulas for caps, swaptions, and basis swaptions. A model specification...... with dependent LIBOR rates is developed that allows for an efficient and accurate calibration to a system of caplet prices....

Affinity Programs and the Real Estate Brokerage Industry

OpenAIRE

G Stacy Sirmans; David A. Macpherson

2001-01-01

This study surveys active real estate brokers obtaining information on involvement in affinity programs and referral/relocation networks. Some results regarding affinity involvement are: (a) 13% of respondents reported affinity affilliations, 75% reported no affiliations, and 12% indicated plans to become involved within the next year; (b) about half having affinity affiliations were involved with 2-4 groups; (c) affinity relationships were most often with membership organizations, corporatio...

Higher fees paid to US physicians drive higher spending for physician services compared to other countries.

Science.gov (United States)

Laugesen, Miriam J; Glied, Sherry A

2011-09-01

Higher health care prices in the United States are a key reason that the nation's health spending is so much higher than that of other countries. Our study compared physicians' fees paid by public and private payers for primary care office visits and hip replacements in Australia, Canada, France, Germany, the United Kingdom, and the United States. We also compared physicians' incomes net of practice expenses, differences in financing the cost of medical education, and the relative contribution of payments per physician and of physician supply in the countries' national spending on physician services. Public and private payers paid somewhat higher fees to US primary care physicians for office visits (27 percent more for public, 70 percent more for private) and much higher fees to orthopedic physicians for hip replacements (70 percent more for public, 120 percent more for private) than public and private payers paid these physicians' counterparts in other countries. US primary care and orthopedic physicians also earned higher incomes ($186,582 and $442,450, respectively) than their foreign counterparts. We conclude that the higher fees, rather than factors such as higher practice costs, volume of services, or tuition expenses, were the main drivers of higher US spending, particularly in orthopedics.

Engineering of bispecific affinity proteins with high affinity for ERBB2 and adaptable binding to albumin.

Directory of Open Access Journals (Sweden)

Johan Nilvebrant

Full Text Available The epidermal growth factor receptor 2, ERBB2, is a well-validated target for cancer diagnostics and therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, and thereby require frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ERBB2-targeting with antibody-like pharmacokinetic properties in a small protein format, we have engineered bispecific ERBB2-binding proteins that are based on a small albumin-binding domain. Phage display selection against ERBB2 was used for identification of a lead candidate, followed by affinity maturation using second-generation libraries. Cell surface display and flow-cytometric sorting allowed stringent selection of top candidates from pools pre-enriched by phage display. Several affinity-matured molecules were shown to bind human ERBB2 with sub-nanomolar affinity while retaining the interaction with human serum albumin. Moreover, parallel selections against ERBB2 in the presence of human serum albumin identified several amino acid substitutions that dramatically modulate the albumin affinity, which could provide a convenient means to control the pharmacokinetics. The new affinity proteins competed for ERBB2-binding with the monoclonal antibody trastuzumab and recognized the native receptor on a human cancer cell line. Hence, high affinity tumor targeting and tunable albumin binding were combined in one small adaptable protein.

Alkali Metal Cation versus Proton and Methyl Cation Affinities: Structure and Bonding Mechanism.

Science.gov (United States)

Boughlala, Zakaria; Fonseca Guerra, Célia; Bickelhaupt, F Matthias

2016-06-01

We have analyzed the structure and bonding of gas-phase Cl-X and [HCl-X](+) complexes for X(+)= H(+), CH3 (+), Li(+), and Na(+), using relativistic density functional theory (DFT). We wish to establish a quantitative trend in affinities of the anionic and neutral Lewis bases Cl(-) and HCl for the various cations. The Cl-X bond becomes longer and weaker along X(+) = H(+), CH3 (+), Li(+), and Na(+). Our main purpose is to understand the heterolytic bonding mechanism behind the intrinsic (i.e., in the absence of solvent) alkali metal cation affinities (AMCA) and how this compares with and differs from those of the proton affinity (PA) and methyl cation affinity (MCA). Our analyses are based on Kohn-Sham molecular orbital (KS-MO) theory in combination with a quantitative energy decomposition analysis (EDA) that pinpoints the importance of the different features in the bonding mechanism. Orbital overlap appears to play an important role in determining the trend in cation affinities.

Using Affinity Diagrams to Evaluate Interactive Prototypes

DEFF Research Database (Denmark)

Lucero, Andrés

2015-01-01

our particular use of affinity diagramming in prototype evaluations. We reflect on a decade’s experience using affinity diagramming across a number of projects, both in industry and academia. Our affinity diagramming process in interaction design has been tailored and consists of four stages: creating...

Insights into structural features determining odorant affinities to honey bee odorant binding protein 14.

Science.gov (United States)

Schwaighofer, Andreas; Pechlaner, Maria; Oostenbrink, Chris; Kotlowski, Caroline; Araman, Can; Mastrogiacomo, Rosa; Pelosi, Paolo; Knoll, Wolfgang; Nowak, Christoph; Larisika, Melanie

2014-04-18

Molecular interactions between odorants and odorant binding proteins (OBPs) are of major importance for understanding the principles of selectivity of OBPs towards the wide range of semiochemicals. It is largely unknown on a structural basis, how an OBP binds and discriminates between odorant molecules. Here we examine this aspect in greater detail by comparing the C-minus OBP14 of the honey bee (Apis mellifera L.) to a mutant form of the protein that comprises the third disulfide bond lacking in C-minus OBPs. Affinities of structurally analogous odorants featuring an aromatic phenol group with different side chains were assessed based on changes of the thermal stability of the protein upon odorant binding monitored by circular dichroism spectroscopy. Our results indicate a tendency that odorants show higher affinity to the wild-type OBP suggesting that the introduced rigidity in the mutant protein has a negative effect on odorant binding. Furthermore, we show that OBP14 stability is very sensitive to the position and type of functional groups in the odorant. Copyright © 2014 Elsevier Inc. All rights reserved.

The Cutting Edge of Affinity Electrophoresis Technology.

Science.gov (United States)

Kinoshita, Eiji; Kinoshita-Kikuta, Emiko; Koike, Tohru

2015-03-18

Affinity electrophoresis is an important technique that is widely used to separate and analyze biomolecules in the fields of biology and medicine. Both quantitative and qualitative information can be gained through affinity electrophoresis. Affinity electrophoresis can be applied through a variety of strategies, such as mobility shift electrophoresis, charge shift electrophoresis or capillary affinity electrophoresis. These strategies are based on changes in the electrophoretic patterns of biological macromolecules that result from interactions or complex-formation processes that induce changes in the size or total charge of the molecules. Nucleic acid fragments can be characterized through their affinity to other molecules, for example transcriptional factor proteins. Hydrophobic membrane proteins can be identified by means of a shift in the mobility induced by a charged detergent. The various strategies have also been used in the estimation of association/disassociation constants. Some of these strategies have similarities to affinity chromatography, in that they use a probe or ligand immobilized on a supported matrix for electrophoresis. Such methods have recently contributed to profiling of major posttranslational modifications of proteins, such as glycosylation or phosphorylation. Here, we describe advances in analytical techniques involving affinity electrophoresis that have appeared during the last five years.

Single-step affinity purification for fungal proteomics.

Science.gov (United States)

Liu, Hui-Lin; Osmani, Aysha H; Ukil, Leena; Son, Sunghun; Markossian, Sarine; Shen, Kuo-Fang; Govindaraghavan, Meera; Varadaraj, Archana; Hashmi, Shahr B; De Souza, Colin P; Osmani, Stephen A

2010-05-01

A single-step protein affinity purification protocol using Aspergillus nidulans is described. Detailed protocols for cell breakage, affinity purification, and depending on the application, methods for protein release from affinity beads are provided. Examples defining the utility of the approaches, which should be widely applicable, are included.

The role of antibody affinity and titre in immunity to Schistosoma mansoni following vaccination with highly irradiated cercariae

International Nuclear Information System (INIS)

Vignali, D.A.A.; Devey, M.E.; Bickle, Q.D.; Taylor, M.G.

1990-01-01

Sera from rabbits and rats vaccinated with highly irradiated cercariae of Schistosoma mansoni (VRabS, VRatS) were found to be of substantially higher affinity than sera from CBA mice vaccinated four times (4 x CVMS), single sex sera (SSS) or chronic infection sera (CIS). In contrast, immunoprecipitation studies demonstrated that sera from vaccinated LA mice (LVMS) recognized 125 I-labelled schistosomular surface antigens more intensely than sera from vaccinated HA mice (HVMS). However, peritoneal macrophages from HA and LA mice in the presence of HVMS, LVMS or 4 x CVMS, and naive macrophages activated in vitro with interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) mediated comparable levels of schistosomula killing in vitro. The experiments described here provide evidence that the titre of antibody rather than its affinity may be a more critical factor in the development of optimal immunity to S. mansoni. (author)

Affinity of antibody secreted by a single cell

International Nuclear Information System (INIS)

Doran, D.M.

1978-01-01

It was the intention of this research to measure the affinity of antibody secreted by a single cell, and to describe the spectrum of affinities displayed in response to antigenic stimulation. The single cell secreting specific antibody was isolated by means of the hemolytic plaque assay. The amount of antibody secreted by the cell was to be measured through the use of a solid phase radioimmunoassay. The affinity of the antibody would be estimated by comparing the diameter of the plaque, and the amount of antibody secreted, with a mathematical theory of the formation of a plaque in agar. As a test system, a solid phase radioimmunoassay was developed for human serum albumin using antibody coupled to Sephadex. A sensitivity of 1 nanogram was attained with this assay. A solid phase radioimmunoassay for mouse immunoglobulin M was developed, using antibody coupled to Sepharose. The sensitivity attained with this assay was only on the order of 10 micrograms. The mouse immunoglobulin M radioimmunoassay was not sensitive enough to measure the amount of antibody secreted by a single cell. From a theoretical equation, the relationship between antibody affinity, plaque diameter and antibody secretion rate was calculated for the experimental conditions used in this research. By assuming a constant antibody secretion rate, an effective binding constant for the antibody was estimated from the average plaque diameters. This effective binding constant was observed to increase during the immune response

Connections between quantized affine algebras and superalgebras

International Nuclear Information System (INIS)

Zhang, R.B.

1992-08-01

Every affine superalgebra with a symmetrizable Cartan matrix is closely related to an ordinary affine algebra with the same Cartan matrix. It is shown that the quantum supergroup associated with the former is essentially isomorphic to the quantum group associated with the latter in an appropriate class of representations. At the classical level, each integrable irreducible highest weight representation of the affine superalgebra has a corresponding irreducible representation of the affine algebra, which has the same weight space decomposition. (author). 5 refs, 3 tabs

Affinity of Iresine herbstii and Brugmansia arborea extracts on different cerebral receptors.

Science.gov (United States)

Nencini, Cristina; Cavallo, Federica; Bruni, Giancarlo; Capasso, Anna; De Feo, Vincenzo; De Martino, Laura; Giorgi, Giorgio; Micheli, Lucia

2006-05-24

Iresine herbstii Hook. (Amaranthaceae) and Brugmansia arborea (L.) Lagerheim (Solanaceae) are used in the northern Peruvian Andes for magic-therapeutical purposes. The traditional healers use Iresine herbstii with the ritual aim to expel bad spirits from the body. Furthermore, Iresine herbstii was used in association with other plants, such as Trichocereus pachanoi Britt. et Rose, for divination, to diagnose diseases, and to take possession of another identity. Also, species of Brugmansia have been reported to be used during ritual practices for magical and curative purposes. Given the above evidence, the aim of the present study is to evaluate if the central effects of Iresine herbstii and Brugmansia arborea could be associated with interaction with SNC receptors. Two Iresine herbstii extracts (methanolic and aqueous) and one Brugmansia arborea aqueous extract were tested for in vitro affinity on 5-HT(1A), 5-HT(2A), 5-HT(2C), D1, D2, alpha(1), and alpha(2) receptors by radioligand binding assays. The biological materials for binding assay (cerebral cortex) were taken from male Sprague-Dawley rats. The extracts affinity for receptors is definite as inhibition percentage of radioligand/receptor binding and measured as the radioactivity of remaining complex radioligand/receptor. The data obtained for Iresine extracts have shown a low affinity for the 5-HT(1A) receptor and no affinity for 5-HT(2A) receptor. Otherwise the methanolic extract showed affinity for 5-HT(2C) receptor (IC(50): 34.78 microg/ml) and for D1 receptor (IC(50): 19.63 microg/ml), instead the Iresine aqueous extract displayed a lower affinity for D1 (48.3% at the maximum concentration tested) and a higher value of affinity for D2 receptors (IC(50): 32.08 microg/ml). The Brugmansia aqueous extract displayed affinity for D1 receptors (IC(50): 17.68 microg/ml), D2 receptors (IC(50): 15.95 microg/ml) and weak affinity for the serotoninergic receptors. None of the three extracts showed relevant affinity

A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent

Directory of Open Access Journals (Sweden)

Lykke Pedersen

2014-01-01

Full Text Available Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs.

Two distinct affinity binding sites for IL-1 on human cell lines

International Nuclear Information System (INIS)

Bensimon, C.; Wakasugi, N.; Tagaya, Y.; Takakura, K.; Yodoi, J.; Tursz, T.; Wakasugi, H.

1989-01-01

We used two human cell lines, NK-like YT-C3 and an EBV-containing B cell line, 3B6, as models to study the receptor(s) for IL-1. Two distinct types of saturable binding sites were found on both cell lines at 37 degrees C. Between 1 pM and 100 pM of 125I-IL-1-alpha concentration, saturable binding sites were detected on the YT-C3 cells with a K of 4 x 10(-11) M. The K found for the IL-1-alpha binding sites on 3B6 cells was 7.5 x 10(-11) M. An additional binding curve was detected above 100 pM on YT-C3 cells with a K of 7 x 10(-9) M and on 3B6 cells with a K of 5 x 10(-9) M. Scatchard plot analysis revealed 600 sites/cell with high affinity binding and 7000 sites/cell with low affinity for YT-C3 cells and 300 sites/cell with high affinity binding and 6000 sites/cell with low affinity for 3B6 cells. At 37 degrees C, the internalization of 125I-labeled IL-1 occurred via both high and low affinity IL-1R on both YT-C3 and 3B6 cells, whereas the rates of internalization for high affinity binding sites on YT-C3 cells were predominant in comparison to that of low affinity binding sites. In chemical cross-linking studies of 125 I-IL-1-alpha to 3B6 and YT-C3 cells, two protein bands were immunoprecipitated with Mr around 85 to 90 kDa leading to an estimation of the Mr of the IL-1R around 68 to 72 kDa. In similar experiments, the Mr found for the IL-1R expressed on the murine T cell line EL4 was slightly higher (around 80 kDa). Whether these distinct affinity binding sites are shared by a single molecule or by various chains remains to be elucidated

The Cutting Edge of Affinity Electrophoresis Technology

Science.gov (United States)

Kinoshita, Eiji; Kinoshita-Kikuta, Emiko; Koike, Tohru

2015-01-01

Affinity electrophoresis is an important technique that is widely used to separate and analyze biomolecules in the fields of biology and medicine. Both quantitative and qualitative information can be gained through affinity electrophoresis. Affinity electrophoresis can be applied through a variety of strategies, such as mobility shift electrophoresis, charge shift electrophoresis or capillary affinity electrophoresis. These strategies are based on changes in the electrophoretic patterns of biological macromolecules that result from interactions or complex-formation processes that induce changes in the size or total charge of the molecules. Nucleic acid fragments can be characterized through their affinity to other molecules, for example transcriptional factor proteins. Hydrophobic membrane proteins can be identified by means of a shift in the mobility induced by a charged detergent. The various strategies have also been used in the estimation of association/disassociation constants. Some of these strategies have similarities to affinity chromatography, in that they use a probe or ligand immobilized on a supported matrix for electrophoresis. Such methods have recently contributed to profiling of major posttranslational modifications of proteins, such as glycosylation or phosphorylation. Here, we describe advances in analytical techniques involving affinity electrophoresis that have appeared during the last five years. PMID:28248262

Affine Fullerene C60 in a GS-Quasigroup

Directory of Open Access Journals (Sweden)

Vladimir Volenec

2014-01-01

Full Text Available It will be shown that the affine fullerene C60, which is defined as an affine image of buckminsterfullerene C60, can be obtained only by means of the golden section. The concept of the affine fullerene C60 will be constructed in a general GS-quasigroup using the statements about the relationships between affine regular pentagons and affine regular hexagons. The geometrical interpretation of all discovered relations in a general GS-quasigroup will be given in the GS-quasigroup C(1/2(1+5.

Comparative Case Studies on Indonesian Higher Education Rankings

Science.gov (United States)

Kurniasih, Nuning; Hasyim, C.; Wulandari, A.; Setiawan, M. I.; Ahmar, A. S.

2018-01-01

The quality of the higher education is the result of a continuous process. There are many indicators that can be used to assess the quality of a higher education. The existence of different indicators makes the different result of university rankings. This research aims to find variables that can connect ranking indicators that are used by Indonesian Ministry of Research, Technology, and Higher Education with indicators that are used by international rankings by taking two kind of ranking systems i.e. Webometrics and 4icu. This research uses qualitative research method with comparative case studies approach. The result of the research shows that to bridge the indicators that are used by Indonesian Ministry or Research, Technology, and Higher Education with web-based ranking system like Webometrics and 4icu so that the Indonesian higher education institutions need to open access towards either scientific or non-scientific that are publicly used into web-based environment. One of the strategies that can be used to improve the openness and access towards scientific work of a university is by involving in open science and collaboration.

Screening for Natural Inhibitors of Topoisomerases I from Rhamnus davurica by Affinity Ultrafiltration and High-Performance Liquid Chromatography–Mass Spectrometry

Science.gov (United States)

Chen, Guilin; Guo, Mingquan

2017-01-01

Topoisomerase I (Topo I) catalyzes topological interconversion of duplex DNA during DNA replication and transcription, and has been deemed as important antineoplastic targets. In this study, the fraction R.d-60 from ethyl acetate extracts of Rhamnus davurica showed higher inhibitory rates against SGC-7901 and HT-29 compared with the R.d-30 fraction in vitro. However, the specific active components of R.d-60 fraction remain elusive. To this end, a method based on bio-affinity ultrafiltration and high performance liquid chromatography/electrospray mass spectrometry (HPLC- ESI-MS/MS) was developed to rapidly screen and identify the Topo I inhibitors in this fraction. The enrichment factors (EFs) were calculated to evaluate the binding affinities between the bioactive constituents and Topo I. As a result, eight ligands were identified and six of which with higher EFs showed more potential antitumor activity. Furthermore, antiproliferative assays in vitro (IC50 values) with two representative candidates (apigenin, quercetin) against SGC-7901, HT-29 and Hep G2 cells were conducted and further validated. Finally, the structure-activity relationships revealed that flavones contain a C2-C3 double bond of C ring exhibited higher bio-affinities to Topo I than those without it. This integrated method combining Topo I ultrafiltration with HPLC-MS/MS proved to be very efficient in rapid screening and identification of potential Topo I inhibitors from the complex extracts of medicinal plants, and could be further explored as a valuable high-throughput screening platform in the early drug discovery stage. PMID:28919906

Affinity Spaces and 21st Century Learning

Science.gov (United States)

Gee, James Paul

2017-01-01

This article discusses video games as "attractors" to "affinity spaces." It argues that affinity spaces are key sites today where people teach and learn 21st Century skills. While affinity spaces are proliferating on the Internet as interest-and-passion-driven sites devoted to a common set of endeavors, they are not new, just…

Structure of Greyhound hemoglobin: origin of high oxygen affinity.

Science.gov (United States)

Bhatt, Veer S; Zaldívar-López, Sara; Harris, David R; Couto, C Guillermo; Wang, Peng G; Palmer, Andre F

2011-05-01

This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.

Generalized Warburg impedance on realistic self-affine fractals ...

Indian Academy of Sciences (India)

Administrator

Generalized Warburg impedance on realistic self-affine fractals: Comparative study of statistically corrugated and isotropic roughness. RAJESH KUMAR and RAMA KANT. Journal of Chemical Sciences, Vol. 121, No. 5, September 2009, pp. 579–588. 1. ( ) c. L. R ω on page 582, column 2, para 2, after eq (8) should read as ...

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

Science.gov (United States)

Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

2011-01-01

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

On the structure of self-affine convex bodies

Energy Technology Data Exchange (ETDEWEB)

Voynov, A S [M. V. Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, Moscow (Russian Federation)

2013-08-31

We study the structure of convex bodies in R{sup d} that can be represented as a union of their affine images with no common interior points. Such bodies are called self-affine. Vallet's conjecture on the structure of self-affine bodies was proved for d = 2 by Richter in 2011. In the present paper we disprove the conjecture for all d≥3 and derive a detailed description of self-affine bodies in R{sup 3}. Also we consider the relation between properties of self-affine bodies and functional equations with a contraction of an argument. Bibliography: 10 titles.

A Novel Fast and Robust Binary Affine Invariant Descriptor for Image Matching

Directory of Open Access Journals (Sweden)

Xiujie Qu

2014-01-01

Full Text Available As the current binary descriptors have disadvantages of high computational complexity, no affine invariance, and the high false matching rate with viewpoint changes, a new binary affine invariant descriptor, called BAND, is proposed. Different from other descriptors, BAND has an irregular pattern, which is based on local affine invariant region surrounding a feature point, and it has five orientations, which are obtained by LBP effectively. Ultimately, a 256 bits binary string is computed by simple random sampling pattern. Experimental results demonstrate that BAND has a good matching result in the conditions of rotating, image zooming, noising, lighting, and small-scale perspective transformation. It has better matching performance compared with current mainstream descriptors, while it costs less time.

The role of antibody affinity and titre in immunity to Schistosoma mansoni following vaccination with highly irradiated cercariae

Energy Technology Data Exchange (ETDEWEB)

Vignali, D.A.A.; Devey, M.E.; Bickle, Q.D.; Taylor, M.G. (London School of Hygiene and Tropical Medicine (UK))

1990-02-01

Sera from rabbits and rats vaccinated with highly irradiated cercariae of Schistosoma mansoni (VRabS, VRatS) were found to be of substantially higher affinity than sera from CBA mice vaccinated four times (4 x CVMS), single sex sera (SSS) or chronic infection sera (CIS). In contrast, immunoprecipitation studies demonstrated that sera from vaccinated LA mice (LVMS) recognized {sup 125}I-labelled schistosomular surface antigens more intensely than sera from vaccinated HA mice (HVMS). However, peritoneal macrophages from HA and LA mice in the presence of HVMS, LVMS or 4 x CVMS, and naive macrophages activated in vitro with interferon-gamma (IFN-{gamma})/lipopolysaccharide (LPS) mediated comparable levels of schistosomula killing in vitro. The experiments described here provide evidence that the titre of antibody rather than its affinity may be a more critical factor in the development of optimal immunity to S. mansoni. (author).

Polynomials associated with equilibria of affine Toda-Sutherland systems

International Nuclear Information System (INIS)

Odake, S; Sasaki, R

2004-01-01

An affine Toda-Sutherland system is a quasi-exactly solvable multi-particle dynamics based on an affine simple root system. It is a 'cross' between two well-known integrable multi-particle dynamics, an affine Toda molecule (exponential potential, periodic nearest-neighbour interaction) and a Sutherland system (inverse sine-square interaction). Polynomials describing the equilibrium positions of affine Toda-Sutherland systems are determined for all affine simple root systems

Different endothelin receptor affinities in dog tissues

International Nuclear Information System (INIS)

Loeffler, B.M.L.; Loehrer, W.

1991-01-01

Endothelin (ET) is a long-lasting potent vasoconstrictor-peptide. Here the authors report different binding affinities of endothelin-1 (ET-1) to ET-receptors of various dog tissues. Crude microsomal fractions were prepared after homogenisation of dog tissues in 50 mM Tris/HCl, 20 mM MnCl2, 1 mM EDTA, pH 7.4 by differential centrifugation. Aliquots of microsomal fractions (70 micrograms of protein) were incubated at 25 degrees C for 180 min in the presence of 20 pM 125I-ET-1 and various concentrations of cold ET-1. Four different ET-1 receptor binding affinities were found: adrenals, cerebrum, liver, heart, skeletal muscle and stomach microsomal membranes contained high affinity binding sites (Kd 50 - 80 pM, Bmax 60 - 250 fmol/mg). In cerebellum and spleen medium affinity ET-1 receptors (Kd 350 pM, Bmax 880 and 1200 fmol/mg respectively) were present. In comparison lung and kidney microsomes contained a low affinity ET-1 receptor (Kd 800 and 880 pM, Bmax 1600 and 350 fmol/mg). Receptors of even lower affinity were present in heart, intestine and liver microsomes with Kd values of 3 - 6 nM

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...... Grassmann code of any level and compute its minimum distance. Further, we ameliorate the results by Beelen concerning the automorphism group of affine Grassmann codes. Finally, we prove that affine Grassmann codes and their duals have the property that they are linear codes generated by their minimum......-weight codewords. This provides a clean analogue of a corresponding result for generalized Reed-Muller codes....

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.

Development of an aptamer-based affinity purification method for vascular endothelial growth factor

Directory of Open Access Journals (Sweden)

Maren Lönne

2015-12-01

Full Text Available Since aptamers bind their targets with high affinity and specificity, they are promising alternative ligands in protein affinity purification. As aptamers are chemically synthesized oligonucleotides, they can be easily produced in large quantities regarding GMP conditions allowing their application in protein production for therapeutic purposes. Several advantages of aptamers compared to antibodies are described in general within this paper. Here, an aptamer directed against the human Vascular Endothelial Growth Factor (VEGF was used as affinity ligand for establishing a purification platform for VEGF in small scale. The aptamer was covalently immobilized on magnetic beads in a controlled orientation resulting in a functional active affinity matrix. Target binding was optimized by introduction of spacer molecules and variation of aptamer density. Further, salt-induced target elution was demonstrated as well as VEGF purification from a complex protein mixture proving the specificity of protein-aptamer binding.

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 id...

Student Engagement, Ideological Contest and Elective Affinity: The Zepke Thesis Reviewed

Science.gov (United States)

Trowler, Paul

2015-01-01

This paper takes up issues raised in two articles by Nick Zepke and portrayed here as "the Zepke thesis". This thesis argues that the literature on, interest in and practices around student engagement in higher education have an elective affinity with neo-liberal ideology. At one level this paper counters many of the assertions that…

Selection of imprinted nanoparticles by affinity chromatography.

Science.gov (United States)

Guerreiro, António R; Chianella, Iva; Piletska, Elena; Whitcombe, Michael J; Piletsky, Sergey A

2009-04-15

Soluble molecularly imprinted nanoparticles were synthesised via iniferter initiated polymerisation and separated by size via gel permeation chromatography. Subsequent fractionation of these particles by affinity chromatography allowed the separation of high affinity fractions from the mixture of nanoparticles. Fractions selected this way possess affinity similar to that of natural antibodies (K(d) 6.6x10(-8)) M and were also able to discriminate between related functional analogues of the template.

Craniomandibular morphology and phylogenetic affinities of panthera atrox

DEFF Research Database (Denmark)

Christiansen, Per; Harris, J.M.

2009-01-01

The great North American Pleistocene pantherine felid Panthera atrox has had a turbulent phylogenetic history, and has been claimed to show affinities to both the jaguar and the tiger; currently, it is most often regarded as a subspecies of the extant lion. The cranial, mandibular, and dental...... morphology of Panthera atrox was compared with those of extant lions, jaguars, and tigers using bivariate, multivariate, and shape analyses. Results indicate that the skull of Panthera atrox shows lion affinities, but also deviates from lions in numerous aspects. Mandibular morphology is more similar...... to jaguars and tigers and, as with cranial morphology, the mandible shows a number of traits not present among extant pantherines. Multivariate analyses grouped Panthera atrox separately from other pantherines. Panthera atrox was no lion, and cannot be assigned to any of the extant pantherines...

The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity.

Science.gov (United States)

Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier; Barman, Ishita; Strop, Pavel; Chin, Sherman Michael; Pham, Amber; Bolton, Gary; McDonough, Dan; Lindquist, Kevin; Pons, Jaume; Rajpal, Arvind

2015-01-01

The neonatal Fc receptor (FcRn) is expressed by cells of epithelial, endothelial and myeloid lineages and performs multiple roles in adaptive immunity. Characterizing the FcRn/IgG interaction is fundamental to designing therapeutic antibodies because IgGs with moderately increased binding affinities for FcRn exhibit superior serum half-lives and efficacy. It has been hypothesized that 2 FcRn molecules bind an IgG homodimer with disparate affinities, yet their affinity constants are inconsistent across the literature. Using surface plasmon resonance biosensor assays that eliminated confounding experimental artifacts, we present data supporting an alternate hypothesis: 2 FcRn molecules saturate an IgG homodimer with identical affinities at independent sites, consistent with the symmetrical arrangement of the FcRn/Fc complex observed in the crystal structure published by Burmeister et al. in 1994. We find that human FcRn binds human IgG1 with an equilibrium dissociation constant (KD) of 760 ± 60 nM (N = 14) at 25°C and pH 5.8, and shows less than 25% variation across the other human subtypes. Human IgG1 binds cynomolgus monkey FcRn with a 2-fold higher affinity than human FcRn, and binds both mouse and rat FcRn with a 10-fold higher affinity than human FcRn. FcRn/IgG interactions from multiple species show less than a 2-fold weaker affinity at 37°C than at 25°C and appear independent of an IgG's variable region. Our in vivo data in mouse and rat models demonstrate that both affinity and avidity influence an IgG's serum half-life, which should be considered when choosing animals, especially transgenic systems, as surrogates.

Contractions of affine spherical varieties

International Nuclear Information System (INIS)

Arzhantsev, I V

1999-01-01

The language of filtrations and contractions is used to describe the class of G-varieties obtainable as the total spaces of the construction of contraction applied to affine spherical varieties, which is well-known in invariant theory. These varieties are local models for arbitrary affine G-varieties of complexity 1 with a one-dimensional categorical quotient. As examples, reductive algebraic semigroups and three-dimensional SL 2 -varieties are considered

Food and value motivation: Linking consumer affinities to different types of food products.

Science.gov (United States)

de Boer, Joop; Schösler, Hanna

2016-08-01

This study uses the consumer affinity concept to examine the multiple motives that may shape consumers' relationships with food. The concept was applied in a study on four broad product types in the Netherlands, which cover a wide range of the market and may each appeal to consumers with different affinities towards foods. These product types may be denoted as 'conventional', 'efficient', 'gourmet' and 'pure'. A comparative analysis, based on Higgins' Regulatory Focus Theory, was performed to examine whether food-related value motivations could explain different consumer affinities for these product types. The affinities of consumers were measured by means of a non-verbal, visual presentation of four samples of food products in a nationwide survey (n = 742) among consumers who were all involved in food purchasing and/or cooking. The affinities found could be predicted fairly well from a number of self-descriptions relating to food and eating, which expressed different combinations of type of value motivation and involvement with food. The analysis demonstrated the contrasting role of high and low involvement as well as the potential complementarity of promotion- and prevention-focused value motivation. It is suggested that knowledge of the relationships between product types, consumer affinities and value motivation can help improve the effectiveness of interventions that seek to promote healthy and sustainable diets in developed countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Blood O2 affinity of a large polar elasmobranch, the Greenland shark Somniosus microcephalus

DEFF Research Database (Denmark)

Herbert, N.A.; Skov, Peter Vilhelm; Tirsgaard, B.

2017-01-01

The Greenland shark (Somniosus microcephalus. Bloch & Schneider 1801) is a polar elasmobranch that is hypothesised to possess a unique metabolic physiology due to its extreme large size, the cold waters it inhabits and its slow swimming lifestyle. Our results therefore provide the first insight...... into the metabolic physiology of this unique shark, with a focus on blood O2 affinity. An evaluation of blood O2 affinity at 2 °C using tonometry revealed a P50 of 11.7 mmHg at a PCO2 of 2.25 mmHg and a Bohr effect (binding sensitivity of blood to pH, ϕ = Δlog P50/ΔpH) of −0.26. A comparative evaluation of blood O2...... affinity across elasmobranch fishes suggests that S. microcephalus has a high blood O2 affinity (i.e., low P50) and a small Bohr effect but these are common traits in sluggish elasmobranch fishes, with little evidence for any relationship of blood O2 affinity to the low metabolic rates, low environmental...

Conformational destabilization of Immunoglobulin G increases the low pH-binding affinity with the Neonatal Fc Receptor

DEFF Research Database (Denmark)

Walters, Benjamin T; Jensen, Pernille Foged; Larraillet, Vincent

2016-01-01

Crystallographic evidence suggests that the pH-dependent affinity of IgG molecules for the neonatal Fc receptor (FcRn) receptor primarily arises from salt bridges involving IgG histidine residues, resulting in moderate affinity at mildly acidic conditions. However, this view does not explain the ......H-dependent affinity in IgG-FcRn interactions and exemplify the important and often ignored role of intrinsic conformational dynamics in a protein ligand, to dictate affinity for biologically important receptors.......Crystallographic evidence suggests that the pH-dependent affinity of IgG molecules for the neonatal Fc receptor (FcRn) receptor primarily arises from salt bridges involving IgG histidine residues, resulting in moderate affinity at mildly acidic conditions. However, this view does not explain...... the diversity in affinity found in IgG variants, such as the YTE mutant (M252Y,S254T,T256E), which increases affinity to FcRn by up to 10×. Here we compare hydrogen exchange measurements at pH 7.0 and pH 5.5 with and without FcRn bound with surface plasmon resonance estimates of dissociation constants and Fc...

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.

The high-affinity peptidoglycan binding domain of Pseudomonas phage endolysin KZ144

Energy Technology Data Exchange (ETDEWEB)

Briers, Yves [Division of Gene Technology, Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B-3001 Leuven (Belgium); Schmelcher, Mathias; Loessner, Martin J. [Institute of Food Science and Nutrition, ETH Zuerich, Schmelzbergstrasse 7, CH-8092 Zuerich (Switzerland); Hendrix, Jelle; Engelborghs, Yves [Laboratory of Biomolecular Dynamics, Department of Chemistry, Katholieke Universiteit Leuven, Celestijnenlaan 200G, B-3001 Leuven (Belgium); Volckaert, Guido [Division of Gene Technology, Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B-3001 Leuven (Belgium); Lavigne, Rob, E-mail: rob.lavigne@biw.kuleuven.be [Division of Gene Technology, Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B-3001 Leuven (Belgium)

2009-05-29

The binding affinity of the N-terminal peptidoglycan binding domain of endolysin KZ144 (PBD{sub KZ}), originating from Pseudomonas aeruginosa bacteriophage {phi}KZ, has been examined using a fusion protein of PBD{sub KZ} and green fluorescent protein (PBD{sub KZ}-GFP). A fluorescence recovery after photobleaching analysis of bound PBD{sub KZ}-GFP molecules showed less than 10% fluorescence recovery in the bleached area within 15 min. Surface plasmon resonance analysis confirmed this apparent high binding affinity revealing an equilibrium affinity constant of 2.95 x 10{sup 7} M{sup -1} for the PBD{sub KZ}-peptidoglycan interaction. This unique domain, which binds to the peptidoglycan of all tested Gram-negative species, was harnessed to improve the specific activity of the peptidoglycan hydrolase domain KMV36C. The chimeric peptidoglycan hydrolase (PBD{sub KZ}-KMV36C) exhibits a threefold higher specific activity than the native catalytic domain (KMV36C). These results demonstrate that the modular assembly of functional domains is a rational approach to improve the specific activity of endolysins from phages infecting Gram-negatives.

Development of a nonlinear model for the prediction of response times of glucose affinity sensors using concanavalin A and dextran and the development of a differential osmotic glucose affinity sensor

Science.gov (United States)

Reis, Louis G.

With the increasing prevalence of diabetes in the United States and worldwide, blood glucose monitoring must be accurate and reliable. Current enzymatic sensors have numerous disadvantages that make them unreliable and unfavorable among patients. Recent research in glucose affinity sensors correct some of the problems that enzymatic sensors experience. Dextran and concanavalin A are two of the more common components used in glucose affinity sensors. When these sensors were first explored, a model was derived to predict the response time of a glucose affinity sensor using concanavalin A and dextran. However, the model assumed the system was linear and fell short of calculating times representative of the response times determined through experimental tests with the sensors. In this work, a new model that uses the Stokes-Einstein Equation to demonstrate the nonlinear behavior of the glucose affinity assay was developed to predict the response times of similar glucose affinity sensors. In addition to the device tested by the original linear model, additional devices were identified and tested with the proposed model. The nonlinear model was designed to accommodate the many different variations between systems. The proposed model was able to accurately calculate response times for sensors using the concanavalin A-dextran affinity assay with respect to the experimentally reported times by the independent research groups. Parameter studies using the nonlinear model were able to identify possible setbacks that could compromise the response of thesystem. Specifically, the model showed that the improper use of asymmetrical membranes could increase the response time by as little as 20% or more as the device is miniaturized. The model also demonstrated that systems using the concanavalin Adextran assay would experience higher response times in the hypoglycemic range. This work attempted to replicate and improve an osmotic glucose affinity sensor. The system was designed to

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.

Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms.

Science.gov (United States)

Yuan, Fenghua; Qian, Liangyue; Zhao, Xinliang; Liu, Jesse Y; Song, Limin; D'Urso, Gennaro; Jain, Chaitanya; Zhang, Yanbin

2012-02-10

The Fanconi anemia complementation group A (FANCA) gene is one of 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. FANCA binds to both single-stranded (ssDNA) and double-stranded (dsDNA) DNAs; however, its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determined that the minimum number of nucleotides required for FANCA recognition is ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5'-flap or 5'-tail on DNA facilitates its interaction with FANCA. A patient-derived FANCA truncation mutant (Q772X) has diminished affinity for both DNA and RNA. In contrast, the complementing C-terminal fragment of Q772X, C772-1455, retains the differentiated nucleic acid-binding activity (RNA > ssDNA > dsDNA), indicating that the nucleic acid-binding domain of FANCA is located primarily at its C terminus, where most disease-causing mutations are found.

Fanconi Anemia Complementation Group A (FANCA) Protein Has Intrinsic Affinity for Nucleic Acids with Preference for Single-stranded Forms*

Science.gov (United States)

Yuan, Fenghua; Qian, Liangyue; Zhao, Xinliang; Liu, Jesse Y.; Song, Limin; D'Urso, Gennaro; Jain, Chaitanya; Zhang, Yanbin

2012-01-01

The Fanconi anemia complementation group A (FANCA) gene is one of 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. FANCA binds to both single-stranded (ssDNA) and double-stranded (dsDNA) DNAs; however, its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determined that the minimum number of nucleotides required for FANCA recognition is ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5′-flap or 5′-tail on DNA facilitates its interaction with FANCA. A patient-derived FANCA truncation mutant (Q772X) has diminished affinity for both DNA and RNA. In contrast, the complementing C-terminal fragment of Q772X, C772–1455, retains the differentiated nucleic acid-binding activity (RNA > ssDNA > dsDNA), indicating that the nucleic acid-binding domain of FANCA is located primarily at its C terminus, where most disease-causing mutations are found. PMID:22194614

New unitary affine-Virasoro constructions

International Nuclear Information System (INIS)

Halpern, M.B.; Kiritsis, E.; Obers, N.A.; Poratti, M.; Yamron, J.P.

1990-01-01

This paper reports on a quasi-systematic investigation of the Virasoro master equation. The space of all affine-Virasoro constructions is organized by K-conjugation into affine-Virasoro nests, and an estimate of the dimension of the space shows that most solutions await discovery. With consistent ansatze for the master equation, large classes of new unitary nests are constructed, including quadratic deformation nests with continuous conformal weights, and unitary irrational central charge nests, which may dominate unitary rational central charge on compact g

PHARMACEUTICAL AND BIOMEDICAL APPLICATIONS OF AFFINITY CHROMATOGRAPHY: RECENT TRENDS AND DEVELOPMENTS

Science.gov (United States)

Hage, David S.; Anguizola, Jeanethe A.; Bi, Cong; Li, Rong; Matsuda, Ryan; Papastavros, Efthimia; Pfaunmiller, Erika; Vargas, John; Zheng, Xiwei

2012-01-01

Affinity chromatography is a separation technique that has become increasingly important in work with biological samples and pharmaceutical agents. This method is based on the use of a biologically-related agent as a stationary phase to selectively retain analytes or to study biological interactions. This review discusses the basic principles behind affinity chromatography and examines recent developments that have occurred in the use of this method for biomedical and pharmaceutical analysis. Techniques based on traditional affinity supports are discussed, but an emphasis is placed on methods in which affinity columns are used as part of HPLC systems or in combination with other analytical methods. General formats for affinity chromatography that are considered include step elution schemes, weak affinity chromatography, affinity extraction and affinity depletion. Specific separation techniques that are examined include lectin affinity chromatography, boronate affinity chromatography, immunoaffinity chromatography, and immobilized metal ion affinity chromatography. Approaches for the study of biological interactions by affinity chromatography are also presented, such as the measurement of equilibrium constants, rate constants, or competition and displacement effects. In addition, related developments in the use of immobilized enzyme reactors, molecularly imprinted polymers, dye ligands and aptamers are briefly considered. PMID:22305083

The Emergent Terrains of "Higher Education Regionalism": How and Why Higher Education Is an Interesting Case for Comparative Regionalism

Science.gov (United States)

Chou, Meng-Hsuan; Ravinet, Pauline

2016-01-01

The introduction of regional political initiatives in the higher education sector symbolizes one of the many aspects of the changing global higher education landscape. Remarkably, these processes have generally escaped comparative scrutiny by scholars researching higher education policy cooperation or regional integration. In this article, we…

Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bear Ursus arctos.

Science.gov (United States)

Revsbech, Inge G; Malte, Hans; Fröbert, Ole; Evans, Alina; Blanc, Stéphane; Josefsson, Johan; Fago, Angela

2013-01-01

During winter hibernation, brown bears (Ursus arctos) reduce basal O(2) consumption rate to ∼25% compared with the active state, while body temperature decreases moderately (to ∼30°C), suggesting a temperature-independent component in their metabolic depression. To establish whether changes in O(2) consumption during hibernation correlate with changes in blood O(2) affinity, we took blood samples from the same six individuals of hibernating and nonhibernating free-ranging brown bears during winter and summer, respectively. A single hemoglobin (Hb) component was detected in all samples, indicating no switch in Hb synthesis. O(2) binding curves measured on red blood cell lysates at 30°C and 37°C showed a less temperature-sensitive O(2) affinity than in other vertebrates. Furthermore, hemolysates from hibernating bears consistently showed lower cooperativity and higher O(2) affinity than their summer counterparts, regardless of the temperature. We found that this increase in O(2) affinity was associated with a significant decrease in the red cell Hb-cofactor 2,3-diphosphoglycerate (DPG) during hibernation to approximately half of the summer value. Experiments performed on purified Hb, to which DPG had been added to match summer and winter levels, confirmed that the low DPG content was the cause of the left shift in the Hb-O(2) equilibrium curve during hibernation. Levels of plasma lactate indicated that glycolysis is not upregulated during hibernation and that metabolism is essentially aerobic. Calculations show that the increase in Hb-O(2) affinity and decrease in cooperativity resulting from decreased red cell DPG may be crucial in maintaining a fairly constant tissue oxygen tension during hibernation in vivo.

Advancement in Higher Education: The Role of Marketing in Building Philanthropic Giving

Science.gov (United States)

McAlexander, James H.; Koenig, Harold F.; DuFault, Beth

2014-01-01

This paper empirically explores ways in which marketers of higher education can contribute to the important task of cultivating alumni philanthropy. Advancement professionals understand that philanthropy is influenced by wealth and affinity. As marketers, we anticipate that our contribution resides with investments in building affinity. Using…

A novel lentiviral scFv display library for rapid optimization and selection of high affinity antibodies.

Science.gov (United States)

Qudsia, Sehar; Merugu, Siva B; Mangukiya, Hitesh B; Hema, Negi; Wu, Zhenghua; Li, Dawei

2018-04-30

Antibody display libraries have become a popular technique to screen monoclonal antibodies for therapeutic purposes. An important aspect of display technology is to generate an optimization library by changing antibody affinity to antigen through mutagenesis and screening the high affinity antibody. In this study, we report a novel lentivirus display based optimization library antibody in which Agtuzumab scFv is displayed on cell membrane of HEK-293T cells. To generate an optimization library, hotspot mutagenesis was performed to achieve diverse antibody library. Based on sequence analysis of randomly selected clones, library size was estimated approximately to be 1.6 × 10 6 . Lentivirus display vector was used to display scFv antibody on cell surface and flow cytometery was performed to check the antibody affinity to antigen. Membrane bound scFv antibodies were then converted to secreted antibody through cre/loxP recombination. One of the mutant clones, M8 showed higher affinity to antigen in flow cytometery analysis. Further characterization of cellular and secreted scFv through western blot showed that antibody affinity was increased by three fold after mutagenesis. This study shows successful construction of a novel antibody library and suggests that hotspot mutagenesis could prove a useful and rapid optimization tool to generate similar libraries with various degree of antigen affinity. Copyright © 2018 Elsevier Inc. All rights reserved.

Two amino acid residues confer different binding affinities of Abelson family kinase SRC homology 2 domains for phosphorylated cortactin.

Science.gov (United States)

Gifford, Stacey M; Liu, Weizhi; Mader, Christopher C; Halo, Tiffany L; Machida, Kazuya; Boggon, Titus J; Koleske, Anthony J

2014-07-11

The closely related Abl family kinases, Arg and Abl, play important non-redundant roles in the regulation of cell morphogenesis and motility. Despite similar N-terminal sequences, Arg and Abl interact with different substrates and binding partners with varying affinities. This selectivity may be due to slight differences in amino acid sequence leading to differential interactions with target proteins. We report that the Arg Src homology (SH) 2 domain binds two specific phosphotyrosines on cortactin, a known Abl/Arg substrate, with over 10-fold higher affinity than the Abl SH2 domain. We show that this significant affinity difference is due to the substitution of arginine 161 and serine 187 in Abl to leucine 207 and threonine 233 in Arg, respectively. We constructed Abl SH2 domains with R161L and S187T mutations alone and in combination and find that these substitutions are sufficient to convert the low affinity Abl SH2 domain to a higher affinity "Arg-like" SH2 domain in binding to a phospho-cortactin peptide. We crystallized the Arg SH2 domain for structural comparison to existing crystal structures of the Abl SH2 domain. We show that these two residues are important determinants of Arg and Abl SH2 domain binding specificity. Finally, we expressed Arg containing an "Abl-like" low affinity mutant Arg SH2 domain (L207R/T233S) and find that this mutant, although properly localized to the cell periphery, does not support wild type levels of cell edge protrusion. Together, these observations indicate that these two amino acid positions confer different binding affinities and cellular functions on the distinct Abl family kinases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Braided affine geometry and q-analogs of wave operators

International Nuclear Information System (INIS)

Gurevich, Dimitri; Saponov, Pavel

2009-01-01

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 U q (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)

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

Affine stochastic mortality

NARCIS (Netherlands)

Schrager, D.F.

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

Importance of Accurate Charges in Binding Affinity Calculations: A Case of Neuraminidase Series

Energy Technology Data Exchange (ETDEWEB)

Park, Kichul; Kyun, Nack Sung; Cho, Art E. [Korea Univ., Sejong (Korea, Republic of)

2013-02-15

It has been shown that calculating atomic charges using quantum mechanical level theory greatly improves the accuracy of docking. A protocol was developed and shown to be effective. That this protocol works is just a manifestation of the fact that electrostatic interactions are important in protein-ligand binding. In order to investigate how the same protocol helps in prediction of binding affinities, we took a series of known cocrystal structures of influenza neuraminidase inhibitors with the receptor and performed docking with Glide SP, Glide XP, and QPLD, the last being a workflow that incorporates QM/MM calculations to replace the fixed atomic charges of force fields with quantum mechanically recalculated ones at a given docking pose, and predicted the binding affinities of each cocrystal. The correlation with experimental binding affinities considerably improved with QPLD compared to Glide SP/XP yielding r{sup 2} = 0.83. The results suggest that for binding sites, such as that of neuraminidase, which are laden with hydrophilic residues, protocols such as QPLD which utilizes QM-based atomic charges can better predict the binding affinities.

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

Science.gov (United States)

Wiesler, Simone C; Weinzierl, Robert O J

2015-01-01

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

Studies on the tumor and organ affinity of /sup 201/Tl

Energy Technology Data Exchange (ETDEWEB)

Mori, H; Ando, I; Takeuchi, T [Kanazawa Univ. (Japan). School of Medicine; Ando, A; Hiraki, T

1980-01-01

In order to evaluate the tumor and organ affinity of /sup 201/Tl, using the Yoshida sarcoma bearing rats, the distribution of /sup 201/Tl/sup +/ in tissues and tumor was examined and compared to /sup 22/Na/sup +/, /sup 42/K/sup +/, /sup 86/Rb/sup +/, /sup 134/Cs/sup +/, and /sup 67/Ga-citrate. /sup 201/Tl/sup +/ showed almost same organ accumulation and kinetics as /sup 42/K/sup +/, /sup 86/Rb/sup +/, /sup 134/Cs, whereas /sup 201/Tl/sup +/ and /sup 22/Na/sup +/ had completely different organ distribution. These results suggest that organ affinity of /sup 201/Tl/sup +/ might be related to active transport, namely Na/sup +/-K/sup +/-ATPase pump mechanism as well as blood flow. However, it appeared to be taken into account the other factors such as different accumulation and clearance rate due to different substrates of organs. Kidney accumulation rate of /sup 201/Tl/sup +/ was much higher than /sup 42/K/sup +/, /sup 86/Rb/sup +/, /sup 134/Cs/sup +/ and about 10 times as /sup 42/K/sup +/. Macroautoradiograms of rat kidneys showed that /sup 201/Tl/sup +/ exhibited an initial high accumulation in the cortex and appeared in the outer cortex, as the cortex cleared of radioactivity. /sup 201/Tl might be interchangeable with K/sup +/ in the tubular system, reabsorbed with more affinity and cleared more slowly than K/sup +/. The tumor accumulation /sup 201/Tl/sup +/ might be related to Na/sup +/-K/sup +/-ATPase pump mechanism as well as other organs. However, in terms of tumor accumulation and concentration ratio to other organs, /sup 201/Tl/sup +/ was inferior to /sup 67/Ga-citrate, although the tumor to blood ratio was identical to that of /sup 67/Ga-citrate. Since /sup 201/Tl/sup + + +/ showed almost same distribution as /sup 201/Tl/sup +/, /sup 201/Tl/sup + + +/ might change into /sup 201/Tl/sup +/ in vivo.

Dynamics of Open Systems with Affine Maps

International Nuclear Information System (INIS)

Zhang Da-Jian; Liu Chong-Long; Tong Dian-Min

2015-01-01

Many quantum systems of interest are initially correlated with their environments and the reduced dynamics of open systems are an interesting while challenging topic. Affine maps, as an extension of completely positive maps, are a useful tool to describe the reduced dynamics of open systems with initial correlations. However, it is unclear what kind of initial state shares an affine map. In this study, we give a sufficient condition of initial states, in which the reduced dynamics can always be described by an affine map. Our result shows that if the initial states of the combined system constitute a convex set, and if the correspondence between the initial states of the open system and those of the combined system, defined by taking the partial trace, is a bijection, then the reduced dynamics of the open system can be described by an affine map. (paper)

Single-Step Affinity Purification for Fungal Proteomics ▿ †

OpenAIRE

Liu, Hui-Lin; Osmani, Aysha H.; Ukil, Leena; Son, Sunghun; Markossian, Sarine; Shen, Kuo-Fang; Govindaraghavan, Meera; Varadaraj, Archana; Hashmi, Shahr B.; De Souza, Colin P.; Osmani, Stephen A.

2010-01-01

A single-step protein affinity purification protocol using Aspergillus nidulans is described. Detailed protocols for cell breakage, affinity purification, and depending on the application, methods for protein release from affinity beads are provided. Examples defining the utility of the approaches, which should be widely applicable, are included.

The Structure of Affine Buildings

CERN Document Server

Weiss, Richard M

2009-01-01

In The Structure of Affine Buildings, Richard Weiss gives a detailed presentation of the complete proof of the classification of Bruhat-Tits buildings first completed by Jacques Tits in 1986. The book includes numerous results about automorphisms, completions, and residues of these buildings. It also includes tables correlating the results in the locally finite case with the results of Tits's classification of absolutely simple algebraic groups defined over a local field. A companion to Weiss's The Structure of Spherical Buildings, The Structure of Affine Buildings is organized around the clas

Spectral affinity in protein networks.

Science.gov (United States)

Voevodski, Konstantin; Teng, Shang-Hua; Xia, Yu

2009-11-29

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. 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. 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 quickly find nodes closest to a queried vertex in any protein

Multiprocessor Real-Time Scheduling with Hierarchical Processor Affinities

OpenAIRE

Bonifaci , Vincenzo; Brandenburg , Björn; D'Angelo , Gianlorenzo; Marchetti-Spaccamela , Alberto

2016-01-01

International audience; Many multiprocessor real-time operating systems offer the possibility to restrict the migrations of any task to a specified subset of processors by setting affinity masks. A notion of " strong arbitrary processor affinity scheduling " (strong APA scheduling) has been proposed; this notion avoids schedulability losses due to overly simple implementations of processor affinities. Due to potential overheads, strong APA has not been implemented so far in a real-time operat...

Higher spin black holes with soft hair

Energy Technology Data Exchange (ETDEWEB)

Grumiller, Daniel [Institute for Theoretical Physics, TU Wien,Wiedner Hauptstrasse 8-10/136, Vienna, A-1040 (Austria); Pérez, Alfredo [Centro de Estudios Científicos (CECs),Av. Arturo Prat 514, Valdivia (Chile); Prohazka, Stefan [Institute for Theoretical Physics, TU Wien,Wiedner Hauptstrasse 8-10/136, Vienna, A-1040 (Austria); Tempo, David; Troncoso, Ricardo [Centro de Estudios Científicos (CECs),Av. Arturo Prat 514, Valdivia (Chile)

2016-10-21

We construct a new set of boundary conditions for higher spin gravity, inspired by a recent “soft Heisenberg hair”-proposal for General Relativity on three-dimensional Anti-de Sitter space. The asymptotic symmetry algebra consists of a set of affine û(1) current algebras. Its associated canonical charges generate higher spin soft hair. We focus first on the spin-3 case and then extend some of our main results to spin-N, many of which resemble the spin-2 results: the generators of the asymptotic W{sub 3} algebra naturally emerge from composite operators of the û(1) charges through a twisted Sugawara construction; our boundary conditions ensure regularity of the Euclidean solutions space independently of the values of the charges; solutions, which we call “higher spin black flowers”, are stationary but not necessarily spherically symmetric. Finally, we derive the entropy of higher spin black flowers, and find that for the branch that is continuously connected to the BTZ black hole, it depends only on the affine purely gravitational zero modes. Using our map to W-algebra currents we recover well-known expressions for higher spin entropy. We also address higher spin black flowers in the metric formalism and achieve full consistency with previous results.

Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding

KAUST Repository

Di Palma, Francesco; Tramontano, Anna

2017-01-01

The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.

Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding

KAUST Repository

Di Palma, Francesco

2017-08-03

The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.

Interest Rates with Long Memory: A Generalized Affine Term-Structure Model

DEFF Research Database (Denmark)

Osterrieder, Daniela

.S. government bonds, we model the time series of the state vector by means of a co-fractional vector autoregressive model. The implication is that yields of all maturities exhibit nonstationary, yet mean-reverting, long-memory behavior of the order d ≈ 0.87. The long-run dynamics of the state vector are driven......We propose a model for the term structure of interest rates that is a generalization of the discrete-time, Gaussian, affine yield-curve model. Compared to standard affine models, our model allows for general linear dynamics in the vector of state variables. In an application to real yields of U...... forecasts that outperform several benchmark models, especially at long forecasting horizons....

Modeling the self-affine structure and optimization conditions of city systems using the idea from fractals

International Nuclear Information System (INIS)

Chen Yanguang; Lin Jingyi

2009-01-01

This paper demonstrates self-affine fractal structure of city systems by means of theoretical and empirical analyses. A Cobb-Douglas-type function (C-D function) of city systems is derived from a general urban response equation, and the partial scaling exponent of the C-D function proved to be the fractal dimension reflecting the self-affine features of city systems. As a case, the self-affine fractal model is applied to the city of Zhengzhou, China, and the result is satisfying. A fractal parameter equation indicative of structural optimization conditions is then obtained from the C-D function. The equation suggests that priority should be given to the development of the urban element with a lower fractal dimension, or a higher partial scaling exponent, for utility maximization. Moreover, the fractal dimensions of different urban elements tend to become equivalent to each other in the long term. Accordingly, it is self-similar fractals rather than self-affine fractals that represent the optimal structure of city systems under ideal conditions.

Affine fractal functions as bases of continuous funtions | Navascues ...

African Journals Online (AJOL)

The objective of the present paper is the study of affine transformations of the plane, which provide self-affine curves as attractors. The properties of these curves depend decisively of the coefficients of the system of affinities involved. The corresponding functions are continuous on a compact interval. If the scale factors are ...

Antibody Affinity Maturation in Fishes—Our Current Understanding

Directory of Open Access Journals (Sweden)

Brad G. Magor

2015-07-01

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

Thermokinetic model of borosilicate glass dissolution: contextual affinity

International Nuclear Information System (INIS)

Advocat, T.; Vernaz, E.; Crovisier, J.L.; Fritz, B.

1989-01-01

Short and long-term geochemical interactions of R7T7 nuclear glass with water at 100 0 C were simulated with the DISSOL thermokinetic computer code. Both the dissolved glass quantity and the resulting water composition, saturation states and mineral quantities produced were calculated as a function of time. The rate equation used in the simulation was first proposed by Aagaard and Helgeson. It simulates a gradually diminishing dissolution rate as the reaction affinity diminishes. The best agreement with 1-year experimental data was obtained with a reaction affinity calculated from silica activity (Grambow's hypothesis) rather than taking into account the activity of all the glass components as proposed by Jantzen and Plodinec. The concept of residual affinity was introduced by Grambow to express the fact that the glass dissolution rate does not cease. We prefer to replace the term residual affinity by contextual affinity, which expresses the influence on the dissolution rate of three factors: the solution chemistry, the metastability of SiO 2 (m), and the possible precipitation of certain aluminosilicates such as zeolites. 19 refs

Affinity Strings: Enterprise Data for Resource Recommendations

Directory of Open Access Journals (Sweden)

Shane Nackerud

2008-12-01

Full Text Available The University of Minnesota Libraries have created a MyLibrary portal, with databases and e-journals targeted to users, based on their affiliations. The University's enterprise authentication system provides an "affinity string", now used to personalize the MyLibrary portal. This affinity string automates discovery of a user's relationship to the University--describing a user's academic department and degree program or position at the University. Affinity strings also provide the Libraries with an anonymized view of resource usage, allowing data collection that respects users' privacy and lays the groundwork for automated recommendation of relevant resources based on the practices and habits of their peers.

Compound immobilization and drug-affinity chromatography.

Science.gov (United States)

Rix, Uwe; Gridling, Manuela; Superti-Furga, Giulio

2012-01-01

Bioactive small molecules act through modulating a yet unpredictable number of targets. It is therefore of critical importance to define the cellular target proteins of a compound as an entry point to understanding its mechanism of action. Often, this can be achieved in a direct fashion by chemical proteomics. As with any affinity chromatography, immobilization of the bait to a solid support is one of the earliest and most crucial steps in the process. Interfering with structural features that are important for identification of a target protein will be detrimental to binding affinity. Also, many molecules are sensitive to heat or to certain chemicals, such as acid or base, and might be destroyed during the process of immobilization, which therefore needs to be not only efficient, but also mild. The subsequent affinity chromatography step needs to preserve molecular and conformational integrity of both bait compound and proteins in order to result in the desired specific enrichment while ensuring a high level of compatibility with downstream analysis by mass spectrometry. Thus, the right choice of detergent, buffer, and protease inhibitors is also essential. This chapter describes a widely applicable procedure for the immobilization of small molecule drugs and for drug-affinity chromatography with subsequent protein identification by mass spectrometry.

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.

Affine coherent states and Toeplitz operators

Science.gov (United States)

Hutníková, Mária; Hutník, Ondrej

2012-06-01

We study a parameterized family of Toeplitz operators in the context of affine coherent states based on the Calderón reproducing formula (= resolution of unity on L_2( {R})) and the specific admissible wavelets (= affine coherent states in L_2( {R})) related to Laguerre functions. Symbols of such Calderón-Toeplitz operators as individual coordinates of the affine group (= upper half-plane with the hyperbolic geometry) are considered. In this case, a certain class of pseudo-differential operators, their properties and their operator algebras are investigated. As a result of this study, the Fredholm symbol algebras of the Calderón-Toeplitz operator algebras for these particular cases of symbols are described. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Coherent states: mathematical and physical aspects’.

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.

Affinity for Poetry and Aesthetic Appreciation of Joyful and Sad Poems.

Science.gov (United States)

Kraxenberger, Maria; Menninghaus, Winfried

2016-01-01

Artworks with sad and affectively negative content have repeatedly been reported to elicit positive aesthetic appreciation. This topic has received much attention both in the history of poetics and aesthetics as well as in recent studies on sad films and sad music. However, poetry and aesthetic evaluations of joyful and sad poetry have received only little attention in empirical studies to date. We collected beauty and liking ratings for 24 sad and 24 joyful poems from 128 participants. Following previous studies, we computed an integrated measure for overall aesthetic appreciation based on the beauty and liking ratings to test for differences in appreciation between joyful and sad poems. Further, we tested whether readers' judgments are related to their affinity for poetry. Results show that sad poems are rated significantly higher for aesthetic appreciation than joyful poems, and that aesthetic appreciation is influenced by the participants' affinity for poetry.

Simulating the influence of plasma protein on measured receptor affinity in biochemical assays reveals the utility of Schild analysis for estimating compound affinity for plasma proteins.

Science.gov (United States)

Blakeley, D; Sykes, D A; Ensor, P; Bertran, E; Aston, P J; Charlton, S J

2015-11-01

Plasma protein binding (PPB) influences the free fraction of drug available to bind to its target and is therefore an important consideration in drug discovery. While traditional methods for assessing PPB (e.g. rapid equilibrium dialysis) are suitable for comparing compounds with relatively weak PPB, they are not able to accurately discriminate between highly bound compounds (typically >99.5%). The aim of the present work was to use mathematical modelling to explore the potential utility of receptor binding and cellular functional assays to estimate the affinity of compounds for plasma proteins. Plasma proteins are routinely added to in vitro assays, so a secondary goal was to investigate the effect of plasma proteins on observed ligand-receptor interactions. Using the principle of conservation of mass and the law of mass action, a cubic equation was derived describing the ligand-receptor complex [LR] in the presence of plasma protein at equilibrium. The model demonstrates the profound influence of PPB on in vitro assays and identifies the utility of Schild analysis, which is usually applied to determine receptor-antagonist affinities, for calculating affinity at plasma proteins (termed KP ). We have also extended this analysis to functional effects using operational modelling and demonstrate that these approaches can also be applied to cell-based assay systems. These mathematical models can potentially be used in conjunction with experimental data to estimate drug-plasma protein affinities in the earliest phases of drug discovery programmes. © 2015 The British Pharmacological Society.

High-Affinity Accumulation of Chloroquine by Mouse Erythrocytes Infected with Plasmodium berghei

Science.gov (United States)

Fitch, Coy D.; Yunis, Norman G.; Chevli, Rekha; Gonzalez, Yolanda

1974-01-01

Washed erythrocytes infected with chloroquine-susceptible (CS) or with chloroquine-resistant (CR) P. berghei were used in model systems in vitro to study the accumulation of chloroquine with high affinity. The CS model could achieve distribution ratios (chloroquine in cells: chloroquine in medium) of 100 in the absence of substrate. 200—300 in the presence of 10 mM pyruvate or lactate, and over 600 in the presence of 1 mM glucose or glycerol. In comparable studies of the CR model, the distribution ratios were 100 in the absence of substrate and 300 or less in the presence of glucose or glycerol. The presence of lactate stimulated chloroquine accumulation in the CR model, whereas the presence of pyruvate did not. Lactate production from glucose and glycerol was undiminished in the CR model, and ATP concentrations were higher than in the CS model. Cold, iodoacetate, 2,4-dinitrophenol, or decreasing pH inhibited chloroquine accumulation in both models. These findings demonstrate substrate involvement in the accumulation of chloroquine with high affinity. In studies of the CS model, certain compounds competitively inhibited chloroquine accumulation, while others did not. This finding is attributable to a specific receptor that imposes structural constraints on the process of accumulation. For chloroquine analogues, the position and length of the side chain, the terminal nitrogen atom of the side chain, and the nitrogen atom in the quinoline ring are important determinants of binding to this receptor. PMID:4600044

Large self-affine fractality in $\\pi^{+}p$ and $K^{+}p$ collisions at 250 GeV/c

CERN Document Server

Agababian, N M

1996-01-01

Taking into account the anisotropy of phase space in multiparticle production, a self-affine analysis of factorial moments was carried out on the NA22 data for $\\pi^{+}p$ and $K^{+}p$ collisions at 250 GeV/$c$. Within the transverse plane, the Hurst exponents measuring the anisotropy are consistent with unit value (i.e. no anisotropy). They are, however, only half that value when the longitudinal direction is compared to the transverse ones. Fractality, indeed, turns out to be self-affine rather than self-similar in multiparticle production. In three-dimensional phase space, power-law scaling is observed to be better realized in self-affine than in self-similar analysis.

Higher spin currents in orthogonal Wolf space

International Nuclear Information System (INIS)

Ahn, Changhyun; Paeng, Jinsub

2015-01-01

For the N=4 superconformal coset theory by ((SO(N+4))/(SO(N)×SU(2)))×U(1) (that contains an orthogonal Wolf space) with N = 4, the N=2 WZW affine current algebra is obtained. The 16 generators (or 11 generators) of the large N=4 linear (or nonlinear) superconformal algebra are described by these WZW affine currents explicitly. Along the line of large N=4 holography, the extra 16 currents with spins (2,(5/2),(5/2),3), ((5/2),3,3,(7/2)), ((5/2),3,3,(7/2)), and (3,(7/2),(7/2),4) are obtained in terms of the WZW affine currents. The lowest spin of this N=4 multiplet is two rather than one, which is for a unitary Wolf space. The operator product expansions between the above 11 currents and these extra 16 higher spin currents are found explicitly. (paper)

Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens

International Nuclear Information System (INIS)

Shyu, Conrad; Cavileer, Timothy D.; Nagler, James J.; Ytreberg, F. Marty

2011-01-01

Environmental estrogens have been the subject of intense research due to their documented detrimental effects on the health of fish and wildlife and their potential to negatively impact humans. A complete understanding of how these compounds affect health is complicated because environmental estrogens are a structurally heterogeneous group of compounds. In this work, computational molecular dynamics simulations were utilized to predict the binding affinity of different compounds using rainbow trout (Oncorhynchus mykiss) estrogen receptors (ERs) as a model. Specifically, this study presents a comparison of the binding affinity of the natural ligand estradiol-17β to the four rainbow trout ER isoforms with that of three known environmental estrogens 17α-ethinylestradiol, bisphenol A, and raloxifene. Two additional compounds, atrazine and testosterone, that are known to be very weak or non-binders to ERs were tested. The binding affinity of these compounds to the human ERα subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17β, bisphenol A binds less strongly to all four receptors, 17α-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the α subtype only. The results also show that atrazine and testosterone are weak or non-binders to the ERs. All of the results are in excellent qualitative agreement with the known in vivo estrogenicity of these compounds in the rainbow trout and other fishes. Computational estimation of binding affinities could be a valuable tool for predicting the impact of environmental estrogens in fish and other animals.

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.

Affine.m—Mathematica package for computations in representation theory of finite-dimensional and affine Lie algebras

Science.gov (United States)

Nazarov, Anton

2012-11-01

In this paper we present Affine.m-a program for computations in representation theory of finite-dimensional and affine Lie algebras and describe implemented algorithms. The algorithms are based on the properties of weights and Weyl symmetry. Computation of weight multiplicities in irreducible and Verma modules, branching of representations and tensor product decomposition are the most important problems for us. These problems have numerous applications in physics and we provide some examples of these applications. The program is implemented in the popular computer algebra system Mathematica and works with finite-dimensional and affine Lie algebras. Catalogue identifier: AENA_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENB_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, UK Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 24 844 No. of bytes in distributed program, including test data, etc.: 1 045 908 Distribution format: tar.gz Programming language: Mathematica. Computer: i386-i686, x86_64. Operating system: Linux, Windows, Mac OS, Solaris. RAM: 5-500 Mb Classification: 4.2, 5. Nature of problem: Representation theory of finite-dimensional Lie algebras has many applications in different branches of physics, including elementary particle physics, molecular physics, nuclear physics. Representations of affine Lie algebras appear in string theories and two-dimensional conformal field theory used for the description of critical phenomena in two-dimensional systems. Also Lie symmetries play a major role in a study of quantum integrable systems. Solution method: We work with weights and roots of finite-dimensional and affine Lie algebras and use Weyl symmetry extensively. Central problems which are the computations of weight multiplicities, branching and fusion coefficients are solved using one general recurrent

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

Quantitative relationship between antibody affinity and antibody avidity

International Nuclear Information System (INIS)

Griswold, W.R.

1987-01-01

The relationship between antibody avidity, measured by the dissociation of the antigen-antibody bond in antigen excess, and antibody affinity was studied. Complexes of radiolabelled antigen and antibody of known affinity were prepared in vitro and allowed to stand for seven days to reach equilibrium. Then nonlabelled antigen in one hundred fold excess was added to dissociate the complexes. After an appropriate incubation the fraction of antigen bound to antibody was measured by the ammonium sulfate precipitation method. The dissociation index was the fraction bound in the experimental sample divided by the fraction bound in the control. The correlation coefficient between the dissociation index and the antibody binding constant was 0.92 for early dissociation and 0.98 for late dissociation. The regression equation relating the binding constant to the dissociation index was K = 6.4(DI) + 6.25, where DI is the late dissociation index and K is the logarithm to the base 10 of the binding constant. There is a high correlation between avidity and affinity of antibody. Antibody affinity can be estimated from avidity data. The stability of antigen-antibody complexes can be predicted from antibody affinity

Thermokinetic model of borosilicate glass dissolution: Contextual affinity

International Nuclear Information System (INIS)

Advocat, T.; Vernaz, E.; Crovisier, J.L.; Fritz, B.

1990-01-01

Short and long-term geochemical interactions of R7T7 nuclear glass with water at 100C were simulated with the DISSOL thermokinetic computer code. Both the dissolved glass quantity and the resulting water composition, saturation states and mineral quantities produced were calculated as a function of time. The rate equation used in the simulation was first proposed by Aagaard and Hegelson: v = k + · S · a( H + ) -n · (1 - e -(A/RT) ). It simulates a gradually diminishing dissolution rate as the reaction affinity diminishes. The best agreement with 1-year experimental data was obtained with a reaction affinity calculated from silica activity (Grambow's hypothesis) rather than taking into account the activity of all the glass components as proposed by Jantzen and Plodinec. The concept of residual affinity was introduced by Grambow to express the fact that the glass dissolution rate does not cease. The authors prefer to replace the term residual affinity by contextual affinity, which expresses the influence on the dissolution rate of three factors: the solution chemistry, the metastability of SiO 2 (m), and the possible precipitation of certain aluminosilicates such as zeolites

Binding affinity and decontamination of dermal decontamination gel to model chemical warfare agent simulants.

Science.gov (United States)

Cao, Yachao; Elmahdy, Akram; Zhu, Hanjiang; Hui, Xiaoying; Maibach, Howard

2018-05-01

Six chemical warfare agent simulants (trimethyl phosphate, dimethyl adipate, 2-chloroethyl methyl sulfide, diethyl adipate, chloroethyl phenyl sulfide and diethyl sebacate) were studied in in vitro human skin to explore relationship between dermal penetration/absorption and the mechanisms of simulant partitioning between stratum corneum (SC) and water as well as between dermal decontamination gel (DDGel) and water. Both binding affinity to and decontamination of simulants using DDGel were studied. Partition coefficients of six simulants between SC and water (Log P SC/w ) and between DDGel and water (Log P DDGel/w ) were determined. Results showed that DDGel has a similar or higher binding affinity to each simulant compared to SC. The relationship between Log P octanol/water and Log P SC/w as well as between Log P octanol/water and Log P DDGel/w demonstrated that partition coefficient of simulants correlated to their lipophilicity or hydrophilicity. Decontamination efficiency results with DDGel for these simulants were consistent with binding affinity results. Amounts of percentage dose of chemicals in DDGel of trimethyl phosphate, dimethyl adipate, 2-chloroethyl methyl sulfide, diethyl adipate, chloroethyl phenyl sulfide and diethyl sebacate were determined to be 61.15, 85.67, 75.91, 53.53, 89.89 and 76.58, with corresponding amounts absorbed in skin of 0.96, 0.65, 1.68, 0.72, 0.57 and 1.38, respectively. In vitro skin decontamination experiments coupled with a dermal absorption study demonstrated that DDGel can efficiently remove chemicals from skin surface, back-extract from the SC, and significantly reduced chemical penetration into skin or systemic absorption for all six simulants tested. Therefore, DDGel offers a great potential as a NextGen skin Decon platform technology for both military and civilian use. Copyright © 2018 John Wiley & Sons, Ltd.

Metal-loaded SBA-16-like silica – Correlation between basicity and affinity towards hydrogen

International Nuclear Information System (INIS)

Ouargli-Saker, R.; Bouazizi, N.; Boukoussa, B.; Barrimo, Diana; Paola-Nunes-Beltrao, Ana; Azzouz, A.

2017-01-01

Highlights: • Metal dispersion in longitudinal channels confers adsorption properties to SBA-16. • Both Fe"0-NPs and Cu"0-NPs seem to be responsible of this effect. • Effect of the repetitive adsorption-desorption cycles on CO_2 and water sorption. • Hydrogen storage on the functionalized materials. - Abstract: Nanoparticles of Cu"o (CuNPs) and Fe"o (FeNPs) were dispersed in SBA-16-like silica, resulting metal-loaded materials (Cu-SBA-16 and Fe-SBA-16) with improved affinity towards hydrogen. Electron microscopy and X-ray diffraction showed that MNP dispersion occurs mainly inside SBA-16 channels. MNP incorporation was found to confer affinity to the silica surface, since higher CO_2 retention capacity (CRC) was registered Cu/SBA-16 and Fe/SBA-16. This was accompanied by a significant improvement of the affinity towards hydrogen, as supported by hydrogen adsorption tests. This was explained in terms of strong hydrogen interaction with MNP and lattice oxygen atoms. The results reported herein open new prospects for SBA-16 as potential adsorbents for hydrogen storage.

Metal-loaded SBA-16-like silica – Correlation between basicity and affinity towards hydrogen

Energy Technology Data Exchange (ETDEWEB)

Ouargli-Saker, R. [Department of Materials Engineering, University of Science and Technology, El M’naouer, BP 1505, Oran (Algeria); Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Bouazizi, N. [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Unité de recherche, Electrochimie, Matériaux et Environnement, Faculté des Sciences de Gabès, Université de Gabès, Cité Erriadh, 6072 Gabès (Tunisia); Boukoussa, B. [Department of Materials Engineering, University of Science and Technology, El M’naouer, BP 1505, Oran (Algeria); Lqamb, Laboratório de Química Analítica Ambiental, Faculdade de Química, Pontifícia Universidade Católica do Rio Grande do Sul (Brazil); Barrimo, Diana [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Paola-Nunes-Beltrao, Ana [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Laboratory of Materials Chemistry L.C.M, University of Oran1 Ahmed Ben Bella, BP 1524, El-Mnaouer, 31000 Oran (Algeria); Azzouz, A., E-mail: azzouz.a@uqam.ca [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada)

2017-07-31

Highlights: • Metal dispersion in longitudinal channels confers adsorption properties to SBA-16. • Both Fe{sup 0}-NPs and Cu{sup 0}-NPs seem to be responsible of this effect. • Effect of the repetitive adsorption-desorption cycles on CO{sub 2} and water sorption. • Hydrogen storage on the functionalized materials. - Abstract: Nanoparticles of Cu{sup o} (CuNPs) and Fe{sup o} (FeNPs) were dispersed in SBA-16-like silica, resulting metal-loaded materials (Cu-SBA-16 and Fe-SBA-16) with improved affinity towards hydrogen. Electron microscopy and X-ray diffraction showed that MNP dispersion occurs mainly inside SBA-16 channels. MNP incorporation was found to confer affinity to the silica surface, since higher CO{sub 2} retention capacity (CRC) was registered Cu/SBA-16 and Fe/SBA-16. This was accompanied by a significant improvement of the affinity towards hydrogen, as supported by hydrogen adsorption tests. This was explained in terms of strong hydrogen interaction with MNP and lattice oxygen atoms. The results reported herein open new prospects for SBA-16 as potential adsorbents for hydrogen storage.

Peptide Binding to HLA Class I Molecules: Homogenous, High-Throughput Screening, and Affinity Assays

DEFF Research Database (Denmark)

Harndahl, Mikkel; Justesen, Sune Frederik Lamdahl; Lamberth, Kasper

2009-01-01

, better signal-to-background ratios, and a higher capacity. They also describe an efficient approach to screen peptides for binding to HLA molecules. For the occasional user, this will serve as a robust, simple peptide-HLA binding assay. For the more dedicated user, it can easily be performed in a high-throughput...... the luminescent oxygen channeling immunoassay technology (abbreviated LOCI and commercialized as AlphaScreen (TM)). Compared with an enzyme-linked immunosorbent assay-based peptide-HLA class I binding assay, the LOCI assay yields virtually identical affinity measurements, although having a broader dynamic range...... screening mode using standard liquid handling robotics and 384-well plates. We have successfully applied this assay to more than 60 different HLA molecules, leading to more than 2 million measurements. (Journal of Biomolecular Screening 2009: 173-180)...

Calculation of protein-ligand binding affinities.

Science.gov (United States)

Gilson, Michael K; Zhou, Huan-Xiang

2007-01-01

Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

Investigation of molybdenum-crosslinker interfaces for affinity based electrochemical biosensing applications

Science.gov (United States)

Kamakoti, Vikramshankar; Shanmugam, Nandhinee Radha; Tanak, Ambalika Sanjeev; Jagannath, Badrinath; Prasad, Shalini

2018-04-01

Molybdenum (Mo) has been investigated for implementation as an electrode material for affinity based biosensing towards devloping flexibe electronic biosensors. Treatment of the native oxide of molybdenum was investigated through two surface treatment strategies namely thiol and carbodiimide crosslinking methods. The binding interaction between cross-linker molecules and Mo electrode surface has been characterized using Fourier Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and optical microscopy. The efficacy of treatment of Mo with its native oxide using carbodiimide cross linking methodology was established. The carbodiimide cross-linking chemistry was found to possess better surface coverage and binding affinity with Molybdenum electrode surface when compared to thiol cross-linking chemistry.Electrochemical characterization of Mo electrode using Electrochemical Impedance Spectroscopy (EIS) and Cyclic Voltametry (CV) techniques was performed to evaluate the effect of ionic properties of solution buffer on the Mo electrode's performance. Affinity based biosensing of C-Reactive Protein (CRP) has been demonstrated on a flexible nanoporous polymeric substrate with detection threshold of 100 pg/ml in synthetic urine buffer medium. The biosensor has been evaluated to be developed as a dipstick based point of care device for detection of biomarkers in urine.

ASIFT: An Algorithm for Fully Affine Invariant Comparison

Directory of Open Access Journals (Sweden)

Guoshen Yu

2011-02-01

Full Text Available If a physical object has a smooth or piecewise smooth boundary, its images obtained by cameras in varying positions undergo smooth apparent deformations. These deformations are locally well approximated by affine transforms of the image plane. In consequence the solid object recognition problem has often been led back to the computation of affine invariant image local features. The similarity invariance (invariance to translation, rotation, and zoom is dealt with rigorously by the SIFT method The method illustrated and demonstrated in this work, Affine-SIFT (ASIFT, simulates a set of sample views of the initial images, obtainable by varying the two camera axis orientation parameters, namely the latitude and the longitude angles, which are not treated by the SIFT method. Then it applies the SIFT method itself to all images thus generated. Thus, ASIFT covers effectively all six parameters of the affine transform.

Applications of Affine and Weyl geometry

CERN Document Server

García-Río, Eduardo; Nikcevic, Stana

2013-01-01

Pseudo-Riemannian geometry is, to a large extent, the study of the Levi-Civita connection, which is the unique torsion-free connection compatible with the metric structure. There are, however, other affine connections which arise in different contexts, such as conformal geometry, contact structures, Weyl structures, and almost Hermitian geometry. In this book, we reverse this point of view and instead associate an auxiliary pseudo-Riemannian structure of neutral signature to certain affine connections and use this correspondence to study both geometries. We examine Walker structures, Riemannia

Theoretical determination of proton affinity differences in zeolites

NARCIS (Netherlands)

Kramer, G.J.; Santen, van R.A.

1993-01-01

An important factor in zeolite catalysis is the proton affinity, i.e., the energy required to remove a proton from the zeolite lattice. Differences in proton affinity are expected to influence the catalytic activity of acid sites, making the catalytically active sites inhomogeneous (within one

Pseudo-affinity chromatography of rumen microbial cellulase on ...

African Journals Online (AJOL)

Pseudo-affinity chromatography of rumen microbial cellulase on Sepharose- Cibacron Blue F3GA. ... African Journal of Biotechnology ... Pseudo affinity adsorption of bioproducts on Sepharose-cibacron blue F3-GA was subjected to rumen microbial enzyme evaluation through batch binding and column chromatography of ...

High-affinity small molecule-phospholipid complex formation: binding of siramesine to phosphatidicacid

DEFF Research Database (Denmark)

Khandelia, Himanshu

2008-01-01

, comparable to the affinities for the binding of small molecule ligands to proteins, was measured for phosphatidic acid (PA, mole fraction of XPA ) 0.2 in phosphatidylcholine vesicles), yielding a molecular partition coefficient of 240 ( 80 × 106. An MD simulation on the siramesine:PA interaction...

Methyl Cation Affinities of Neutral and Anionic Maingroup-Element Hydrides: Trends Across the Periodic Table and Correlation with Proton Affinities

NARCIS (Netherlands)

Mulder, R. Joshua; Guerra, Celia Fonseca; Bickelhaupt, F. Matthias

2010-01-01

We have computed the methyl cation affinities in the gas phase of archetypal anionic and neutral bases across the periodic table using ZORA-relativistic density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. The main purpose of this work is to provide the methyl cation affinities (and

Enhanced bacterial affinity of PVDF membrane: its application as improved sea water sampling tool for environmental monitoring.

Science.gov (United States)

Kumar, Sweta Binod; Sharnagat, Preeti; Manna, Paramita; Bhattacharya, Amit; Haldar, Soumya

2017-02-01

Isolation of diversified bacteria from seawater is a major challenge in the field of environmental microbiology. In the present study, an attempt has been made to select specific membrane with improved property of attaching diversified bacteria. Initially, different concentrations (15, 18, and 20% W/W) of polysulfone (PSF) were used to check their affinity for the attachment of selected gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria. Among these, 20% W/W PSF showed maximum attachment. Therefore, membrane prepared with other materials such as polyvinylidene fluoride (PVDF) and polyether sulfone (PES) were used with the same concentration (20% W/W) to check their improved bacterial attachment property. Comparative study of bacterial attachment on three different membranes revealed that PVDF possessed the highest affinity towards both the groups of bacteria. This property was confirmed by different analytical methods viz. contact angle, atomic force microscopy, zeta potential, and flux study and further validated with seawater samples collected from seven sites of western coast and Lakshadweep island of India, using Biolog EcoPlate™. All the samples showed that bacterial richness and diversity was high in PVDF membrane in comparison to surrounding seawater samples. Interestingly, affinity for more diversified bacteria was reported to be higher in water sample with less turbidity and low bacteria load. This finding can facilitate the development of PVDF (20% W/W) membrane as a simple, cheap, and less labor intensive environmental sampling tool for the isolation of diversified bacteria from seawater sample wih different physiochemical properties. Graphical abstract ᅟ.

Mathematical analysis of frontal affinity chromatography in particle and membrane configurations.

Science.gov (United States)

Tejeda-Mansir, A; Montesinos, R M; Guzmán, R

2001-10-30

The scaleup and optimization of large-scale affinity-chromatographic operations in the recovery, separation and purification of biochemical components is of major industrial importance. The development of mathematical models to describe affinity-chromatographic processes, and the use of these models in computer programs to predict column performance is an engineering approach that can help to attain these bioprocess engineering tasks successfully. Most affinity-chromatographic separations are operated in the frontal mode, using fixed-bed columns. Purely diffusive and perfusion particles and membrane-based affinity chromatography are among the main commercially available technologies for these separations. For a particular application, a basic understanding of the main similarities and differences between particle and membrane frontal affinity chromatography and how these characteristics are reflected in the transport models is of fundamental relevance. This review presents the basic theoretical considerations used in the development of particle and membrane affinity chromatography models that can be applied in the design and operation of large-scale affinity separations in fixed-bed columns. A transport model for column affinity chromatography that considers column dispersion, particle internal convection, external film resistance, finite kinetic rate, plus macropore and micropore resistances is analyzed as a framework for exploring further the mathematical analysis. Such models provide a general realistic description of almost all practical systems. Specific mathematical models that take into account geometric considerations and transport effects have been developed for both particle and membrane affinity chromatography systems. Some of the most common simplified models, based on linear driving-force (LDF) and equilibrium assumptions, are emphasized. Analytical solutions of the corresponding simplified dimensionless affinity models are presented. Particular

Generalized Warburg impedance on realistic self-affine fractals ...

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... We analyse the problem of impedance for a diffusion controlled charge transfer process across an irregular interface. These interfacial irregularities are characterized as two class of random fractals: (i) a statistically isotropic self-affine fractals and (ii) a statistically corrugated self-affine fractals.

Weak affinity chromatography for evaluation of stereoisomers in early drug discovery.

Science.gov (United States)

Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Svensson, Susanne; Ohlson, Sten; Isaksson, Roland

2013-07-01

In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.

Generalized Warburg impedance on realistic self-affine fractals

Indian Academy of Sciences (India)

We analyse the problem of impedance for a diffusion controlled charge transfer process across an irregular interface. These interfacial irregularities are characterized as two class of random fractals: (i) a statistically isotropic self-affine fractals and (ii) a statistically corrugated self-affine fractals. The information about the ...

Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model

Directory of Open Access Journals (Sweden)

Mittelmann Hans D

2010-01-01

Full Text Available Abstract Background The binding of peptide fragments of extracellular peptides to class II MHC is a crucial event in the adaptive immune response. Each MHC allotype generally binds a distinct subset of peptides and the enormous number of possible peptide epitopes prevents their complete experimental characterization. Computational methods can utilize the limited experimental data to predict the binding affinities of peptides to class II MHC. Results We have developed the Regularized Thermodynamic Average, or RTA, method for predicting the affinities of peptides binding to class II MHC. RTA accounts for all possible peptide binding conformations using a thermodynamic average and includes a parameter constraint for regularization to improve accuracy on novel data. RTA was shown to achieve higher accuracy, as measured by AUC, than SMM-align on the same data for all 17 MHC allotypes examined. RTA also gave the highest accuracy on all but three allotypes when compared with results from 9 different prediction methods applied to the same data. In addition, the method correctly predicted the peptide binding register of 17 out of 18 peptide-MHC complexes. Finally, we found that suboptimal peptide binding registers, which are often ignored in other prediction methods, made significant contributions of at least 50% of the total binding energy for approximately 20% of the peptides. Conclusions The RTA method accurately predicts peptide binding affinities to class II MHC and accounts for multiple peptide binding registers while reducing overfitting through regularization. The method has potential applications in vaccine design and in understanding autoimmune disorders. A web server implementing the RTA prediction method is available at http://bordnerlab.org/RTA/.

Affine pairings on ARM

NARCIS (Netherlands)

Acar, T.; Lauter, K.; Naehrig, M.; Shumow, D.

2011-01-01

Pairings on elliptic curves are being used in an increasing number of cryptographic applications on many different devices and platforms, but few performance numbers for cryptographic pairings have been reported on embedded and mobile devices. In this paper we give performance numbers for affine and

Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections.

Science.gov (United States)

Yoshimi, T; Kawabata, S; Taira, S; Okuno, A; Mikawa, R; Murayama, S; Tanaka, K; Takikawa, O

2015-11-07

A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of small molecules. Candidate molecules showing specific affinity for the tissue section are identified by imaging mass spectrometry (IMS). As an example application, we screened over a thousand compounds against Alzheimer's disease (AD) brain tissue and identified several compounds with high affinity for AD brain sections containing tau deposits compared to age-matched controls. It should also be possible to use AIMS to isolate chemical compounds with affinity for tissue structures or components that have been extensively modified by events such as oxidation, phosphorylation, acetylation, aggregation, racemization or truncation, for example, due to aging. It may also be applicable to biomarker screening programs.

New polymer-supported ion-complexing agents: Design, preparation and metal ion affinities of immobilized ligands

International Nuclear Information System (INIS)

Alexandratos, Spiro D.

2007-01-01

Polymer-supported reagents are comprised of crosslinked polymer networks that have been modified with ligands capable of selective metal ion complexation. Applications of these polymers are in environmental remediation, ion chromatography, sensor technology, and hydrometallurgy. Bifunctional polymers with diphosphonate/sulfonate ligands have a high selectivity for actinide ions. The distribution coefficient for the uranyl ion from 1 M nitric acid is 70,000, compared to 900 for the monophosphonate/sulfonate polymer and 200 for the sulfonic acid ion-exchange resin. A bifunctional trihexyl/triethylammonium polymer has a high affinity and selectivity for pertechnetate and perchlorate anions from groundwater. In one example, its distribution coefficient for perchlorate ions in the presence of competing anions is 3,300,000, compared to 203,180 for a commercially available anion-exchange resin. Polystyrene modified with N-methyl-D-glucamine ligands is capable of selectively complexing arsenate from groundwater. It complexes 99% of the arsenate present in a solution of 100 mg/L arsenate with 560 mg/L sulfate ions. Its selectivity is retained even in the presence of 400 mg/L phosphate. There is no affinity for arsenate above pH 9, allowing for the polymer to be regenerated with moderate alkali solution. In studies aimed at developing a Hg(II)-selective resin, simple amine resins were found to have a high Hg(II) affinity and that affinity is dependent upon the solution pH and the counterion

Modeling the binding affinity of structurally diverse industrial chemicals to carbon using the artificial intelligence approaches.

Science.gov (United States)

Gupta, Shikha; Basant, Nikita; Rai, Premanjali; Singh, Kunwar P

2015-11-01

Binding affinity of chemical to carbon is an important characteristic as it finds vast industrial applications. Experimental determination of the adsorption capacity of diverse chemicals onto carbon is both time and resource intensive, and development of computational approaches has widely been advocated. In this study, artificial intelligence (AI)-based ten different qualitative and quantitative structure-property relationship (QSPR) models (MLPN, RBFN, PNN/GRNN, CCN, SVM, GEP, GMDH, SDT, DTF, DTB) were established for the prediction of the adsorption capacity of structurally diverse chemicals to activated carbon following the OECD guidelines. Structural diversity of the chemicals and nonlinear dependence in the data were evaluated using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. The generalization and prediction abilities of the constructed models were established through rigorous internal and external validation procedures performed employing a wide series of statistical checks. In complete dataset, the qualitative models rendered classification accuracies between 97.04 and 99.93%, while the quantitative models yielded correlation (R(2)) values of 0.877-0.977 between the measured and the predicted endpoint values. The quantitative prediction accuracies for the higher molecular weight (MW) compounds (class 4) were relatively better than those for the low MW compounds. Both in the qualitative and quantitative models, the Polarizability was the most influential descriptor. Structural alerts responsible for the extreme adsorption behavior of the compounds were identified. Higher number of carbon and presence of higher halogens in a molecule rendered higher binding affinity. Proposed QSPR models performed well and outperformed the previous reports. A relatively better performance of the ensemble learning models (DTF, DTB) may be attributed to the strengths of the bagging and boosting algorithms which enhance the predictive accuracies. The

Structural Insight inot the low Affinity Between Thermotoga maritima CheA and CheB Compared to their Escherichia coli/Salmonella typhimurium Counterparts

Energy Technology Data Exchange (ETDEWEB)

S Park; B Crane

2011-12-31

CheA-mediated CheB phosphorylation and the subsequent CheB-mediated demethylation of the chemoreceptors are important steps required for the bacterial chemotactic adaptation response. Although Escherichia coli CheB has been reported to interact with CheA competitively against CheY, we have observed that Thermotoga maritima CheB has no detectable CheA-binding. By determining the CheY-like domain crystal structure of T. maritima CheB, and comparing against the T. maritima CheY and Salmonella typhimurium CheB structures, we propose that the two consecutive glutamates in the {beta}4/{alpha}4 loop of T. maritima CheB that is absent in T. maritima CheY and in E. coli/S. typhimurium CheB may be one factor contributing to the low CheA affinity.

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.

Characterization of self-affinity in the global regime

Science.gov (United States)

Neimark, Alexander V.

1994-11-01

Methods for characterization of self-affine surfaces and measurements of their roughness exponents H are developed. It is shown that for smoothed surfaces, which underwent particular coarse graining or averaging of the small-scale fluctuations, the excess surface area Sex and the mean square root radius of curvature ac are related by two distinct asymptotic power laws if ac is well below or well above a certain crossover scale acr. In the local regime of self-affinity, when acSex~(ac/acr)-(1-H). In the global regime of self-affinity, when ac>>acr, Sex~(ac/acr)-2(1-H)/(2-H). The former scaling relationship is consistent with the well known definition of local fractal dimensions dloc=dtop+1-H. The latter scaling relationship offers alternatives for characterization of self-affinity over large scales by means of excess dimensions defined as dex=dtop+2(1-H)/(2-H) and can be used for determination of roughness exponents from the measurements provided in the global regime. The thermodynamic method of fractal analysis, proposed earlier for self-similar surfaces (A.V. Neimark, Pis'ma Zh. Eksp. Teor. Fiz. 51, 535 (1990) [JETP Lett. 51, 607 (1990)]; Physica A 191, 258 (1992)), is extended for self-affine surfaces for determination of fractal dimensions and roughness exponents from adsorption and capillary experimental data.

Irreversible blockade of the high and low affinity (3H) naloxone binding sites by C-6 derivatives of morphinane-6-ones

International Nuclear Information System (INIS)

Krizsan, D.; Varga, E.; Benyhe, S.; Szucs, M.; Borsodi, A.; Hosztafi, S.

1991-01-01

C-6 derivatives-hydrazones, phenylhydrazones, dinitrophenylhydrazones, oximes and semicarbazones - of morphinane-6-ones were synthesized and their binding characteristics were studied on rat brain membranes. The dihydromorphinone and oxymorphone derivatives compete for the ( 3 H)naloxone binding sites with high affinity, while the dihydrocodeinone and oxycodone derivatives are less potent. The affinity of the new compounds is decreased for the delta sites as compared to the parent ligands. The ligands bearing bulky substituents also bind with low affinity to the kappa sites. The modification decreased the Na + -index of compounds indicating their mixed agonist-antagonist character. The dihydromorphinone derivatives are all capable to block irreversibly the high affinity binding site of ( 3 H)naloxone, whereas the dihydrocodeinone derivatives block irreversibly the low affinity site. A possible mechanism for the inhibition is suggested

Femtomolar Ln(III) affinity in peptide-based ligands containing unnatural chelating amino acids.

Science.gov (United States)

Niedźwiecka, Agnieszka; Cisnetti, Federico; Lebrun, Colette; Delangle, Pascale

2012-05-07

The incorporation of unnatural chelating amino acids in short peptide sequences leads to lanthanide-binding peptides with a higher stability than sequences built exclusively from natural residues. In particular, the hexadentate peptide P(22), which incorporates two unnatural amino acids Ada(2) with aminodiacetate chelating arms, showed picomolar affinity for Tb(3+). To design peptides with higher denticity, expected to show higher affinity for Ln(3+), we synthesized the novel unnatural amino acid Ed3a(2) which carries an ethylenediamine triacetate side-chain and affords a pentadentate coordination site. The synthesis of the derivative Fmoc-Ed3a(2)(tBu)(3)-OH, with appropriate protecting groups for direct use in the solid phase peptide synthesis (Fmoc strategy), is described. The two high denticity peptides P(HD2) (Ac-Trp-Ed3a(2)-Pro-Gly-Ada(2)-Gly-NH(2)) and P(HD5) (Ac-Trp-Ada(2)-Pro-Gly-Ed3a(2)-Gly-NH(2)) led to octadentate Tb(3+) complexes with femtomolar stability in water. The position of the high denticity amino acid Ed3a(2) in the hexapeptide sequence appears to be critical for the control of the metal complex speciation. Whereas P(HD5) promotes the formation of polymetallic species in excess of Ln(3+), P(HD2) forms exclusively the mononuclear complex. The octadentate coordination of Tb(3+) by both P(HD) leads to total dehydration of the metal ion in the mononuclear complexes with long luminescence lifetimes (>2 ms). Hence, we demonstrated that unnatural amino acids carrying polyaminocarboxylate side-chains are interesting building blocks to design high affinity Ln-binding peptides. In particular the novel peptide P(HD2) forms a unique octadentate Tb(3+) complex with femtomolar stability in water and an improvement of the luminescence properties with respect to the trisaquo TbP(22) complex by a factor of 4.

The serotonin transporter: Examination of the changes in transporter affinity induced by ligand binding

International Nuclear Information System (INIS)

Humphreys, C.J.

1989-01-01

The plasmalemmal serotonin transporter uses transmembrane gradients of Na + , Cl - and K + to accumulate serotonin within blood platelets. Transport is competitively inhibited by the antidepressant imipramine. Like serotonin transport, imipramine binding requires Na + . Unlike serotonin, however, imipramine does not appear to be transported. To gain insight into the mechanism of serotonin transport the author have analyzed the influences of Na + and Cl - , the two ions cotransported with serotonin, on both serotonin transport and the interaction of imipramine and other antidepressant drugs with the plasmalemmal serotonin transporter of human platelets. Additionally, the author have synthesized, purified and characterized the binding of 2-iodoimipramine to the serotonin transporter. Finally, the author have conducted a preliminary study of the inhibition of serotonin transport and imipramine binding produced by dicyclohexylcarbodiimide. My results reveal many instances of positive heterotropic cooperativity in ligand binding to the serotonin transporter. Na + binding enhances the transporters affinity for imipramine and several other antidepressant drugs, and also increases the affinity for Cl - . Cl - enhances the transporters affinity for imipramine, as well as for Na + . At concentrations in the range of its K M for transport serotonin is a competitive inhibitor of imipramine binding. At much higher concentrations, however, serotonin also inhibits imipramines dissociation rate constant. This latter effect which is Na + -independent and species specific, is apparently produced by serotonin binding at a second, low affinity site on, or near, the transporter complex. Iodoimipramine competitively inhibit both [ 3 H]imipramine binding and [ 3 H]serotonin transport

Methyl cation affinities of neutral and anionic maingroup-element hydrides: trends across the periodic table and correlation with proton affinities.

Science.gov (United States)

Mulder, R Joshua; Guerra, Célia Fonseca; Bickelhaupt, F Matthias

2010-07-22

We have computed the methyl cation affinities in the gas phase of archetypal anionic and neutral bases across the periodic table using ZORA-relativistic density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. The main purpose of this work is to provide the methyl cation affinities (and corresponding entropies) at 298 K of all anionic (XH(n-1)(-)) and neutral bases (XH(n)) constituted by maingroup-element hydrides of groups 14-17 and the noble gases (i.e., group 18) along the periods 2-6. The cation affinity of the bases decreases from H(+) to CH(3)(+). To understand this trend, we have carried out quantitative bond energy decomposition analyses (EDA). Quantitative correlations are established between the MCA and PA values.

QUALITY ASSURANCE SYSTEMS IN POLISH AND UKRAINIAN HIGHER EDUCATION. A COMPARATIVE ANALYSIS

Directory of Open Access Journals (Sweden)

Marta Tutko

2015-02-01

Full Text Available The article deals with the progress made to develop external and internal quality assurance systems in Polish and Ukrainian higher education in the European Higher Education Area background. The focus of the paper is on the extent to which quality assurance systems in these countries are following the Standards and Guidelines for Quality Assurance in the European Higher Education Area. Furthermore, internal and external quality assur-ance in the European context is presented in the article. The authors of the article also conducted a comparative analysis of quality assurance systems in Polish and Ukrainian higher education.

DAYA ANTIBAKTERI EKSTRAK ETANOL DAUN SENGGANI (Melastoma affine D. Don

Directory of Open Access Journals (Sweden)

Ika Trisharyanti Dian Kusumowati

2014-08-01

Full Text Available Melastoma affine D. Don had some activities such as anthelmintic, antibacteria, antiinfiammation, antifungal, and antitumor. The aims of this research was determine antibacteria activity of ethanolic extract of Melastoma affine D. Don. The antimicrobial activity was tested by solid dilution method to get Minimum Inhibition Concentration (MIC. The compounds in Melastoma affine D. Don was analyzed by tube test method and Thin Layer Chromatography (TLC with chloroform : methanol : formic acid (8,5:1,5:0,5 as mobile phase and silica gel GF254 as stationary phase. The result showed ethanolic extract of Melastoma affine D. Don contains alkaloid, polyphenol, fiavonoid, saponin, and essential oil. The MIC of Senggani against Staphylococcus aureus was 2% and 3% against Escherichia coli and the extract could not inhibit Staphylococcus aureus and Escherichia coli multiresistant until concentration 7% extract ethanol. Keywords: Melastoma affine D. Don, Staphylococcus aureus, Escherichia coli

Affine analogues of the Sasaki-Shchepetilov connection

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Maria Robaszewska

2016-07-01

Full Text Available For two-dimensional manifold M with locally symmetric connection ∇ and with ∇-parallel volume element vol one can construct a flat connection on the vector bundle TM⊕E, where E is a trivial bundle. The metrizable case, when M is a Riemannian manifold of constant curvature, together with its higher dimension generalizations, was studied by A.V. Shchepetilov [J. Phys. A: 36 (2003, 3893-3898]. This paper deals with the case of non-metrizable locally symmetric connection. Two flat connections on TM⊕(R⨯M and two on TM⊕(R2⨯M are constructed. It is shown that two of those connections - one from each pair - may be identified with the standard flat connection in RN, after suitable local affine embedding of (M,∇ into RN.

Modeling DNA affinity landscape through two-round support vector regression with weighted degree kernels

KAUST Repository

Wang, Xiaolei

2014-12-12

Background: A quantitative understanding of interactions between transcription factors (TFs) and their DNA binding sites is key to the rational design of gene regulatory networks. Recent advances in high-throughput technologies have enabled high-resolution measurements of protein-DNA binding affinity. Importantly, such experiments revealed the complex nature of TF-DNA interactions, whereby the effects of nucleotide changes on the binding affinity were observed to be context dependent. A systematic method to give high-quality estimates of such complex affinity landscapes is, thus, essential to the control of gene expression and the advance of synthetic biology. Results: Here, we propose a two-round prediction method that is based on support vector regression (SVR) with weighted degree (WD) kernels. In the first round, a WD kernel with shifts and mismatches is used with SVR to detect the importance of subsequences with different lengths at different positions. The subsequences identified as important in the first round are then fed into a second WD kernel to fit the experimentally measured affinities. To our knowledge, this is the first attempt to increase the accuracy of the affinity prediction by applying two rounds of string kernels and by identifying a small number of crucial k-mers. The proposed method was tested by predicting the binding affinity landscape of Gcn4p in Saccharomyces cerevisiae using datasets from HiTS-FLIP. Our method explicitly identified important subsequences and showed significant performance improvements when compared with other state-of-the-art methods. Based on the identified important subsequences, we discovered two surprisingly stable 10-mers and one sensitive 10-mer which were not reported before. Further test on four other TFs in S. cerevisiae demonstrated the generality of our method. Conclusion: We proposed in this paper a two-round method to quantitatively model the DNA binding affinity landscape. Since the ability to modify

Growth and mortality of larval Myctophum affine (Myctophidae, Teleostei).

Science.gov (United States)

Namiki, C; Katsuragawa, M; Zani-Teixeira, M L

2015-04-01

The growth and mortality rates of Myctophum affine larvae were analysed based on samples collected during the austral summer and winter of 2002 from south-eastern Brazilian waters. The larvae ranged in size from 2·75 to 14·00 mm standard length (L(S)). Daily increment counts from 82 sagittal otoliths showed that the age of M. affine ranged from 2 to 28 days. Three models were applied to estimate the growth rate: linear regression, exponential model and Laird-Gompertz model. The exponential model best fitted the data, and L(0) values from exponential and Laird-Gompertz models were close to the smallest larva reported in the literature (c. 2·5 mm L(S)). The average growth rate (0·33 mm day(-1)) was intermediate among lanternfishes. The mortality rate (12%) during the larval period was below average compared with other marine fish species but similar to some epipelagic fishes that occur in the area. © 2015 The Fisheries Society of the British Isles.

Computation of piecewise affine terminal cost functions for model predictive control

NARCIS (Netherlands)

Brunner, F.D.; Lazar, M.; Allgöwer, F.; Fränzle, Martin; Lygeros, John

2014-01-01

This paper proposes a method for the construction of piecewise affine terminal cost functions for model predictive control (MPC). The terminal cost function is constructed on a predefined partition by solving a linear program for a given piecewise affine system, a stabilizing piecewise affine

Investigations into the binding affinities of different human 5-HT4 receptor splice variants.

Science.gov (United States)

Irving, Helen R; Tochon-Danguy, Nathalie; Chinkwo, Kenneth A; Li, Jian G; Grabbe, Carmen; Shapiro, Marina; Pouton, Colin W; Coupar, Ian M

2010-01-01

This study examined whether the drug-receptor-binding sites of 5 selected human 5-HT(4) receptor splice variants [h5-HT4(a), h5-HT4(b), h5-HT4(c), h5-HT4(d) and h5-HT4(g)] display preferential affinities towards agonists. The agonists selected on the basis of chemical diversity and clinical relevance were: 5-HT4 benzamides, renzapride, zacopride and prucalopride; the benzimidazolones, DAU 6236 and BIMU 1; the aromatic ketone, RS67333, and the indole carbazimidamide tegaserod. The rank order of affinities ranging across the splice variants was: tegaserod (pKi: 7.38-7.91) > or = Y-36912 (pKi: 7.03-7.85) = BIMU 1 (pKi: 6.92-7.78) > or = DAU 6236 (pKi: 6.79-7.99) > or = 5-HT (pKi: 5.82-7.29) > or = 5-MeOT (pKi: 5.64-6.83) > or = renzapride (pKi: 4.85-5.56). We obtained affinity values for the 5-HT4(b), (d) and (g) variants for RS67333 (pKi: 7:48-8.29), prucalopride (pKi: 6.86-7.37) and zacopride (pKi: 5.88-7.0). These results indicate that the ligands interact with the same conserved site in each splice variant. Some splice variants have a higher affinity for certain agonists and the direction of selectivity followed a common trend of lowest affinity at the (d) variant. However, this trend was not evident in functional experiments. Our findings suggest that it may be possible to design splice variant selective ligands, which may be of relevance for experimental drugs but may be difficult to develop clinically. 2010 S. Karger AG, Basel.

Affinity Labeling of Membrane Receptors Using Tissue-Penetrating Radiations

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Franklin C. Wong

2013-01-01

Full Text Available Photoaffinity labeling, a useful in vivo biochemical tool, is limited when applied in vivo because of the poor tissue penetration by ultraviolet (UV photons. This study investigates affinity labeling using tissue-penetrating radiation to overcome the tissue attenuation and irreversibly label membrane receptor proteins. Using X-ray (115 kVp at low doses (<50 cGy or Rad, specific and irreversible binding was found on striatal dopamine transporters with 3 photoaffinity ligands for dopamine transporters, to different extents. Upon X-ray exposure (115 kVp, RTI-38 and RTI-78 ligands showed irreversible and specific binding to the dopamine transporter similar to those seen with UV exposure under other conditions. Similarly, gamma rays at higher energy (662 keV also affect irreversible binding of photoreactive ligands to peripheral benzodiazepine receptors (by PK14105 and to the dopamine (D2 membrane receptors (by azidoclebopride, respectively. This study reports that X-ray and gamma rays induced affinity labeling of membrane receptors in a manner similar to UV with photoreactive ligands of the dopamine transporter, D2 dopamine receptor (D2R, and peripheral benzodiazepine receptor (PBDZR. It may provide specific noninvasive irreversible block or stimulation of a receptor using tissue-penetrating radiation targeting selected anatomic sites.

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

Exploring Girls' Science Affinities Through an Informal Science Education Program

Science.gov (United States)

Todd, Brandy; Zvoch, Keith

2017-10-01

This study examines science interests, efficacy, attitudes, and identity—referred to as affinities, in the context of an informal science outreach program for girls. A mixed methods design was used to explore girls' science affinities before, during, and after participation in a cohort-based summer science camp. Multivariate analysis of survey data revealed that girls' science affinities varied as a function of the joint relationship between family background and number of years in the program, with girls from more affluent families predicted to increase affinities over time and girls from lower income families to experience initial gains in affinities that diminish over time. Qualitative examination of girls' perspectives on gender and science efficacy, attitudes toward science, and elements of science identities revealed a complex interplay of gendered stereotypes of science and girls' personal desires to prove themselves knowledgeable and competent scientists. Implications for the best practice in fostering science engagement and identities in middle school-aged girls are discussed.

Characteristics of the interaction of calcium with casein submicelles as determined by analytical affinity chromatography

International Nuclear Information System (INIS)

Jang, H.D.; Swaisgood, H.E.

1990-01-01

Interaction of calcium with casein submicelles was investigated in CaCl2 and calcium phosphate buffers and with synthetic milk salt solutions using the technique of analytical affinity chromatography. Micelles that had been prepared by size exclusion chromatography with glycerolpropyl controlled-pore glass from fresh raw skim milk that had never been cooled, were dialyzed at room temperature against calcium-free imidazole buffer, pH 6.7. Resulting submicelles were covalently immobilized on succinamidopropyl controlled-pore glass (300-nm pore size). Using 45Ca to monitor the elution retardation, the affinity of free Ca2+ and calcium salt species was determined at temperatures of 20 to 40 degrees C and pH 6.0 to 7.5. Increasing the pH in this range or increasing the temperature strengthened the binding of calcium to submicelles, similar to previous observations with individual caseins. However, the enthalpy change obtained from the temperature dependence was considerably greater than that reported for alpha s1- and beta-caseins. Furthermore, the elution profiles for 45Ca in milk salt solutions were decidedly different from those in CaCl2 or calcium phosphate buffers and the affinities were also greater. For example, at pH 6.7 and 30 degrees C the average dissociation constant for the submicelle-calcium complex is 0.074 mM for CaCl2 and calcium phosphate buffers, vs 0.016 mM for the milk salt solution. The asymmetric frontal boundaries and higher average affinities observed with milk salts may be due to binding of calcium salts with greater affinity in addition to the binding of free Ca2+ in these solutions

Affinity chromatography with pseudobiospecific ligands on high-performance supports for purification of proteins of biotechnological interest

Directory of Open Access Journals (Sweden)

N.B. Iannucci

2003-03-01

Full Text Available High-performance affinity matrices were obtained by attaching pseudobiospecific ligands to hollow-fibre membranes. The neutral protease contained in FlavourzymeTM was purified to homogeneity with Yellow 4R-HE affinity hollow-fibre membranes. Immobilisation of Red HE-3B allowed purification of a milk-clotting enzyme obtained by solid-state culture of Mucor bacilliformis. Copper immobilisation through iminodiacetic acid allowed fractionation of Biocon Bioconcentrated PlusTM to separate the pectinesterase-containing fraction. The productivity of the developed processes - 1900, 94 and 750 U/ml.min, respectively - was 10- to 15-fold higher than that achieved with the same ligands immobilised on agarose-based soft gels, mainly due to the shortening of the purification processes.

Exact S-matrices for dn+1(2) affine Toda solitons and their bound states

International Nuclear Information System (INIS)

Gandenberger, G.M.; MacKay, N.J.

1995-01-01

We conjecture an exact S-matrix for the scattering of solitons in d n+1 (2) affine Toda field theory in terms of the R-matrix of the quantum group U q (c n (1) ). From this we construct the scattering amplitudes for all scalar bound states (breathers) of the theory. This S-matrix conjecture is justified by detailed examination of its pole structure. We show that a breather-particle identification holds by comparing the S-matrix elements for the lowest breathers with the S-matrix for the quantum particles in real affine Toda field theory, and discuss the implications for various forms of duality. (orig.)

Determining the binding affinity of therapeutic monoclonal antibodies towards their native unpurified antigens in human serum.

Directory of Open Access Journals (Sweden)

Christine Bee

Full Text Available Monoclonal antibodies (mAbs are a growing segment of therapeutics, yet their in vitro characterization remains challenging. While it is essential that a therapeutic mAb recognizes the native, physiologically occurring epitope, the generation and selection of mAbs often rely on the use of purified recombinant versions of the antigen that may display non-native epitopes. Here, we present a method to measure both, the binding affinity of a therapeutic mAb towards its native unpurified antigen in human serum, and the antigen's endogenous concentration, by combining the kinetic exclusion assay and Biacore's calibration free concentration analysis. To illustrate the broad utility of our method, we studied a panel of mAbs raised against three disparate soluble antigens that are abundant in the serum of healthy donors: proprotein convertase subtilisin/kexin type 9 (PCSK9, progranulin (PGRN, and fatty acid binding protein (FABP4. We also determined the affinity of each mAb towards its purified recombinant antigen and assessed whether the interactions were pH-dependent. Of the six mAbs studied, three did not appear to discriminate between the serum and recombinant forms of the antigen; one mAb bound serum antigen with a higher affinity than recombinant antigen; and two mAbs displayed a different affinity for serum antigen that could be explained by a pH-dependent interaction. Our results highlight the importance of taking pH into account when measuring the affinities of mAbs towards their serum antigens, since the pH of serum samples becomes increasingly alkaline upon aerobic handling.

Affine pairings on ARM

NARCIS (Netherlands)

Acar, T.; Lauter, K.; Naehrig, M.; Shumow, D.; Abdalla, M.; Lange, T.

2013-01-01

We report on relative performance numbers for affine and projective pairings on a dual-core Cortex A9 ARM processor. Using a fast inversion in the base field and doing inversion in extension fields by using the norm map to reduce to inversions in smaller fields, we find a very low ratio of

Affine planes, ternary rings, and examples of non-Desarguesian planes

OpenAIRE

Ivanov, Nikolai V.

2016-01-01

The paper is devoted to a detailed self-contained exposition of a part of the theory of affine planes leading to a construction of affine (or, equivalently, projective) planes not satisfying the Desarques axiom. It is intended to complement the introductory expositions of the theory of affine and projective planes. A novelty of our exposition is a new notation for the ternary operation in a ternary ring, much more suggestive than the standard one.

Fermionic construction of vertex operators for twisted affine algebras

International Nuclear Information System (INIS)

Frappat, L.; Sorba, P.; Sciarrino, A.

1988-03-01

We construct vertex operator representations of the twisted affine algebras in terms of fermionic (or parafermionic in some cases) elementary fields. The folding method applied to the extended Dynkin diagrams of the affine algebras allows us to determine explicitly these fermionic fields as vertex operators

Excited state electron affinity calculations for aluminum

Science.gov (United States)

Hussein, Adnan Yousif

2017-08-01

Excited states of negative aluminum ion are reviewed, and calculations of electron affinities of the states (3s^23p^2)^1D and (3s3p^3){^5}{S}° relative to the (3s^23p)^2P° and (3s3p^2)^4P respectively of the neutral aluminum atom are reported in the framework of nonrelativistic configuration interaction (CI) method. A priori selected CI (SCI) with truncation energy error (Bunge in J Chem Phys 125:014107, 2006) and CI by parts (Bunge and Carbó-Dorca in J Chem Phys 125:014108, 2006) are used to approximate the valence nonrelativistic energy. Systematic studies of convergence of electron affinity with respect to the CI excitation level are reported. The calculated value of the electron affinity for ^1D state is 78.675(3) meV. Detailed Calculations on the ^5S°c state reveals that is 1216.8166(3) meV below the ^4P state.

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 ...

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.

Affine-projective field laws

International Nuclear Information System (INIS)

Murphy, G.L.

1975-01-01

The general topic of geometric unified field theories is discussed in the first section. Some reasons are given for pursuing such theories, and some criticisms are considered. The second section develops the fundamental equations of a purely affine theory which is invariant under projective transformations of the affine connection. This theory is a generalization of that of Schrodinger. Possible identifications for the space-time metric are considered in Sec. III. Sections IV and V deal with the limits of pure gravitation and electrodynamics. In the symmetric limit, Einstein's vacuum equations with cosmological term are recovered. The theory also contains a generalized electrodynamic set of equations which is very similar to the Born-Infeld set. In the weak-field approximation, a finite mass must be attributed to the photon. The problem of motion for charges is discussed here, and it is argued that criticisms of unified field theories because of a supposed inability to produce the Lorentz force law are probably not justified. Three more speculative sections deal with possible explanations of nuclear forces, the spin-torsion relation, and particle structure

PRINCIPLES OF AFFINITY-BASED BIOSENSORS

Science.gov (United States)

Despite the amount of resources that have been invested by national and international academic, government, and commercial sectors to develop affinity-based biosensor products, little obvious success has been realized through commercialization of these devices for specific applic...

Polynomial Primal-Dual Cone Affine Scaling for Semidefinite Programming

NARCIS (Netherlands)

A.B. Berkelaar (Arjan); J.F. Sturm; S. Zhang (Shuzhong)

1996-01-01

textabstractIn this paper we generalize the primal--dual cone affine scaling algorithm of Sturm and Zhang to semidefinite programming. We show in this paper that the underlying ideas of the cone affine scaling algorithm can be naturely applied to semidefinite programming, resulting in a new

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

Role of β/δ101Gln in Regulating the Effect of Temperature and Allosteric Effectors on Oxygen Affinity in Woolly Mammoth Hemoglobin†

Science.gov (United States)

Yuan, Yue; Byrd, Catherine; Shen, Tong-Jian; Simplaceanu, Virgil; Tam, Tsuey Chyi S.; Ho, Chien

2013-01-01

The oxygen affinity of woolly mammoth hemoglobin (rHb WM) is less affected by temperature change than that of Asian elephant hemoglobin (rHb AE) or human adult hemoglobin (Hb A). We report here a biochemical-biophysical study of Hb A, rHb AE, rHb WM and three rHb WM mutants with amino acid substitutions at β/δ101 (β/δ101Gln→Glu, Lys, or Asp) plus a double and a triple mutant, designed to clarify the role of the β/δ101 residue. The β/δ101Gln residue is important for responding to allosteric effectors, such as phosphate, inositol hexaphosphate (IHP), and chloride. The rHb WM mutants studied generally have higher affinity for oxygen under various conditions of pH, temperature, and salt concentration, and in the presence or absence of organic phosphate, than do rHb WM, rHb AE and Hb A. Titrations for the O2 affinity of these mutant rHbs as a function of chloride concentration indicate a lower heterotopic effect of this anion due to the replacement of β/δ101Gln in rHb WM. The alkaline Bohr effect of rHb WM and its mutants is reduced by 20–50% compared to that of Hb A and is independent of changes in temperature, in contrast to what has been observed in the hemoglobins of most mammalian species, including human. The results of our study on the temperature dependence of the O2 affinity of rHb WM and its mutant rHbs illustrate the important role of β/δ101Gln in regulating the functional properties of these hemoglobins. PMID:24228693

Detection-Guided Fast Affine Projection Channel Estimator for Speech Applications

Directory of Open Access Journals (Sweden)

Yan Wu Jennifer

2007-04-01

Full Text Available In various adaptive estimation applications, such as acoustic echo cancellation within teleconferencing systems, the input signal is a highly correlated speech. This, in general, leads to extremely slow convergence of the NLMS adaptive FIR estimator. As a result, for such applications, the affine projection algorithm (APA or the low-complexity version, the fast affine projection (FAP algorithm, is commonly employed instead of the NLMS algorithm. In such applications, the signal propagation channel may have a relatively low-dimensional impulse response structure, that is, the number m of active or significant taps within the (discrete-time modelled channel impulse response is much less than the overall tap length n of the channel impulse response. For such cases, we investigate the inclusion of an active-parameter detection-guided concept within the fast affine projection FIR channel estimator. Simulation results indicate that the proposed detection-guided fast affine projection channel estimator has improved convergence speed and has lead to better steady-state performance than the standard fast affine projection channel estimator, especially in the important case of highly correlated speech input signals.

Self-affinity in the dengue fever time series

Science.gov (United States)

Azevedo, S. M.; Saba, H.; Miranda, J. G. V.; Filho, A. S. Nascimento; Moret, M. A.

2016-06-01

Dengue is a complex public health problem that is common in tropical and subtropical regions. This disease has risen substantially in the last three decades, and the physical symptoms depict the self-affine behavior of the occurrences of reported dengue cases in Bahia, Brazil. This study uses detrended fluctuation analysis (DFA) to verify the scale behavior in a time series of dengue cases and to evaluate the long-range correlations that are characterized by the power law α exponent for different cities in Bahia, Brazil. The scaling exponent (α) presents different long-range correlations, i.e. uncorrelated, anti-persistent, persistent and diffusive behaviors. The long-range correlations highlight the complex behavior of the time series of this disease. The findings show that there are two distinct types of scale behavior. In the first behavior, the time series presents a persistent α exponent for a one-month period. For large periods, the time series signal approaches subdiffusive behavior. The hypothesis of the long-range correlations in the time series of the occurrences of reported dengue cases was validated. The observed self-affinity is useful as a forecasting tool for future periods through extrapolation of the α exponent behavior. This complex system has a higher predictability in a relatively short time (approximately one month), and it suggests a new tool in epidemiological control strategies. However, predictions for large periods using DFA are hidden by the subdiffusive behavior.

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

Affine Toda equations and solutions in the homogeneous grading

Czech Academy of Sciences Publication Activity Database

Zuevsky, Alexander

2018-01-01

Roč. 542, April 1 (2018), s. 149-161 ISSN 0024-3795 Institutional support: RVO:67985840 Keywords : affine Lie gebras * affine Toda modes * solitons Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.973, year: 2016 https://www.sciencedirect.com/science/article/pii/S0024379517302100

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...... charged metal ions such as Fe3+, Ga3+, Al3+, Zr4+, and Ti4+ has made it possible to enrich phosphorylated peptides from peptide samples. However, the selectivity of most of the metal ions is limited, when working with highly complex samples, e.g., whole-cell extracts, resulting in contamination from...

Satake diagrams of affine Kac-Moody algebras

Energy Technology Data Exchange (ETDEWEB)

Tripathy, L K [S B R Government Womens' College, Berhampur, Orissa 760 001 (India); Pati, K C [Department of Physics, Khallikote College, Berhampur, Orissa 760 001 (India)

2006-02-10

Satake diagrams of affine Kac-Moody algebras (untwisted and twisted) are obtained from their Dynkin diagrams. These diagrams give a classification of restricted root systems associated with these algebras. In the case of simple Lie algebras, these root systems and Satake diagrams correspond to symmetric spaces which have recently found many physical applications in quantum integrable systems, quantum transport problems, random matrix theories etc. We hope these types of root systems may have similar applications in theoretical physics in future and may correspond to symmetric spaces analogue of affine Kac-Moody algebras if they exist.

Supervised machine learning techniques to predict binding affinity. A study for cyclin-dependent kinase 2.

Science.gov (United States)

de Ávila, Maurício Boff; Xavier, Mariana Morrone; Pintro, Val Oliveira; de Azevedo, Walter Filgueira

2017-12-09

Here we report the development of a machine-learning model to predict binding affinity based on the crystallographic structures of protein-ligand complexes. We used an ensemble of crystallographic structures (resolution better than 1.5 Å resolution) for which half-maximal inhibitory concentration (IC 50 ) data is available. Polynomial scoring functions were built using as explanatory variables the energy terms present in the MolDock and PLANTS scoring functions. Prediction performance was tested and the supervised machine learning models showed improvement in the prediction power, when compared with PLANTS and MolDock scoring functions. In addition, the machine-learning model was applied to predict binding affinity of CDK2, which showed a better performance when compared with AutoDock4, AutoDock Vina, MolDock, and PLANTS scores. Copyright © 2017 Elsevier Inc. All rights reserved.

Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

International Nuclear Information System (INIS)

Di Paolo, T.; Falardeau, P.

1987-01-01

The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p 3 H]-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-[β-γ-imino]triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables

An Inverse Relationship Links Temperature and Substrate Apparent Affinity in the Ion-Coupled Cotransporters rGAT1 and KAAT1

Directory of Open Access Journals (Sweden)

Antonio Peres

2012-11-01

Full Text Available The effects of temperature on the operation of two ion-coupled cotransporters of the SLC6A family, namely rat GAT1 (SLC6A1 and KAAT1 (SLC6A19 from Manduca sexta, have been studied by electrophysiological means in Xenopus laevis oocytes expressing these proteins. The maximal transport-associated current (Imax and the apparent substrate affinity (K05 were measured. In addition to the expected increase in transport rate (Q10 = 3–6, both transporters showed greater K05 values (i.e., a decrease in apparent affinity at higher temperatures. The transport efficiency, estimated as Imax/K05, increased at negative potentials in both transporters, but did not show statistically significant differences with temperature. The observation that the apparent substrate affinity is inversely related to the transport rate suggests a kinetic regulation of this parameter. Furthermore, the present results indicate that the affinities estimated at room temperature for mammalian cotransporters may not be simply extrapolated to their physiological operating conditions.

Set-Membership Proportionate Affine Projection Algorithms

Directory of Open Access Journals (Sweden)

Stefan Werner

2007-01-01

Full Text Available Proportionate adaptive filters can improve the convergence speed for the identification of sparse systems as compared to their conventional counterparts. In this paper, the idea of proportionate adaptation is combined with the framework of set-membership filtering (SMF in an attempt to derive novel computationally efficient algorithms. The resulting algorithms attain an attractive faster converge for both situations of sparse and dispersive channels while decreasing the average computational complexity due to the data discerning feature of the SMF approach. In addition, we propose a rule that allows us to automatically adjust the number of past data pairs employed in the update. This leads to a set-membership proportionate affine projection algorithm (SM-PAPA having a variable data-reuse factor allowing a significant reduction in the overall complexity when compared with a fixed data-reuse factor. Reduced-complexity implementations of the proposed algorithms are also considered that reduce the dimensions of the matrix inversions involved in the update. Simulations show good results in terms of reduced number of updates, speed of convergence, and final mean-squared error.

Alkali Metal Cation Affinities of Anionic Main Group-Element Hydrides Across the Periodic Table.

Science.gov (United States)

Boughlala, Zakaria; Fonseca Guerra, Célia; Bickelhaupt, F Matthias

2017-10-05

We have carried out an extensive exploration of gas-phase alkali metal cation affinities (AMCA) of archetypal anionic bases across the periodic system using relativistic density functional theory at ZORA-BP86/QZ4P//ZORA-BP86/TZ2P. AMCA values of all bases were computed for the lithium, sodium, potassium, rubidium and cesium cations and compared with the corresponding proton affinities (PA). One purpose of this work is to provide an intrinsically consistent set of values of the 298 K AMCAs of all anionic (XH n-1 - ) constituted by main group-element hydrides of groups 14-17 along the periods 2-6. In particular, we wish to establish the trend in affinity for a cation as the latter varies from proton to, and along, the alkali cations. Our main purpose is to understand these trends in terms of the underlying bonding mechanism using Kohn-Sham molecular orbital theory together with a quantitative bond energy decomposition analyses (EDA). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

ODE/IM correspondence and Bethe ansatz for affine Toda field equations

Directory of Open Access Journals (Sweden)

Katsushi Ito

2015-07-01

Full Text Available We study the linear problem associated with modified affine Toda field equation for the Langlands dual gˆ∨, where gˆ is an untwisted affine Lie algebra. The connection coefficients for the asymptotic solutions of the linear problem are found to correspond to the Q-functions for g-type quantum integrable models. The ψ-system for the solutions associated with the fundamental representations of g leads to Bethe ansatz equations associated with the affine Lie algebra gˆ. We also study the A2r(2 affine Toda field equation in massless limit in detail and find its Bethe ansatz equations as well as T–Q relations.

Mutational analysis of affinity and selectivity of kringle-tetranectin interaction. Grafting novel kringle affinity ontp the trtranectin lectin scaffold

DEFF Research Database (Denmark)

Graversen, Jonas Heilskov; Jacobsen, C; Sigurskjold, B W

2000-01-01

-type lectin-like domain of tetranectin, involving Lys-148, Glu-150, and Asp-165, which mediates calcium-sensitive binding to plasminogen kringle 4. Here, we investigate the effect of conservative substitutions of these and a neighboring amino acid residue. Substitution of Thr-149 in tetranectin...... with a tyrosine residue considerably increases the affinity for plasminogen kringle 4, and, in addition, confers affinity for plasminogen kringle 2. As shown by isothermal titration calorimetry analysis, this new interaction is stronger than the binding of wild-type tetranectin to plasminogen kringle 4...

Mycobacterium tuberculosis nucleoid-associated DNA-binding protein H-NS binds with high-affinity to the Holliday junction and inhibits strand exchange promoted by RecA protein.

Science.gov (United States)

Sharadamma, N; Harshavardhana, Y; Singh, Pawan; Muniyappa, K

2010-06-01

A number of studies have shown that the structure and composition of bacterial nucleoid influences many a processes related to DNA metabolism. The nucleoid-associated proteins modulate not only the DNA conformation but also regulate the DNA metabolic processes such as replication, recombination, repair and transcription. Understanding of how these processes occur in the context of Mycobacterium tuberculosis nucleoid is of considerable medical importance because the nucleoid structure may be constantly remodeled in response to environmental signals and/or growth conditions. Many studies have concluded that Escherichia coli H-NS binds to DNA in a sequence-independent manner, with a preference for A-/T-rich tracts in curved DNA; however, recent studies have identified the existence of medium- and low-affinity binding sites in the vicinity of the curved DNA. Here, we show that the M. tuberculosis H-NS protein binds in a more structure-specific manner to DNA replication and repair intermediates, but displays lower affinity for double-stranded DNA with relatively higher GC content. Notably, M. tuberculosis H-NS was able to bind Holliday junction (HJ), the central recombination intermediate, with substantially higher affinity and inhibited the three-strand exchange promoted by its cognate RecA. Likewise, E. coli H-NS was able to bind the HJ and suppress DNA strand exchange promoted by E. coli RecA, although much less efficiently compared to M. tuberculosis H-NS. Our results provide new insights into a previously unrecognized function of H-NS protein, with implications for blocking the genome integration of horizontally transferred genes by homologous and/or homeologous recombination.

Higher holonomies: comparing two constructions

DEFF Research Database (Denmark)

Schaetz, Florian; Arias Abad, Camilo

2015-01-01

, there are the higher holonomies associated with flat superconnections as studied by Igusa [7], Block–Smith [3] and Arias Abad–Schätz [1]. We first explain how by truncating the latter construction one obtains examples of the former. Then we prove that the two-dimensional holonomies provided by the two approaches...

Integrable deformations of affine Toda theories and duality

International Nuclear Information System (INIS)

Fateev, V.A.

1996-01-01

We introduce and study five series of one-parameter families of two-dimensional integrable quantum field theories. These theories have a Lagrangian description in terms of the massive Thirring model coupled with non-simply laced affine Toda theories. Perturbative calculations, analysis of the factorized scattering theory and the Bethe ansatz technique are used to show that these field theories possess the dual representation available for the perturbative analysis in the strong coupling limit. The dual theory can be formulated as the non-linear sigma model with Witten's Euclidean black hole metric (complex sinh-Gordon theory) coupled with non-simply laced affine Toda theories. Lie algebras associated with these ''dual'' Toda theories belong to the dual series of affine algebras but have a smaller rank. The exact relation between coupling constants in the dual theories is conjectured. (orig.)

PANDA: Protein function prediction using domain architecture and affinity propagation.

Science.gov (United States)

Wang, Zheng; Zhao, Chenguang; Wang, Yiheng; Sun, Zheng; Wang, Nan

2018-02-22

We developed PANDA (Propagation of Affinity and Domain Architecture) to predict protein functions in the format of Gene Ontology (GO) terms. PANDA at first executes profile-profile alignment algorithm to search against PfamA, KOG, COG, and SwissProt databases, and then launches PSI-BLAST against UniProt for homologue search. PANDA integrates a domain architecture inference algorithm based on the Bayesian statistics that calculates the probability of having a GO term. All the candidate GO terms are pooled and filtered based on Z-score. After that, the remaining GO terms are clustered using an affinity propagation algorithm based on the GO directed acyclic graph, followed by a second round of filtering on the clusters of GO terms. We benchmarked the performance of all the baseline predictors PANDA integrates and also for every pooling and filtering step of PANDA. It can be found that PANDA achieves better performances in terms of area under the curve for precision and recall compared to the baseline predictors. PANDA can be accessed from http://dna.cs.miami.edu/PANDA/ .

2D Affine and Projective Shape Analysis.

Science.gov (United States)

Bryner, Darshan; Klassen, Eric; Huiling Le; Srivastava, Anuj

2014-05-01

Current techniques for shape analysis tend to seek invariance to similarity transformations (rotation, translation, and scale), but certain imaging situations require invariance to larger groups, such as affine or projective groups. Here we present a general Riemannian framework for shape analysis of planar objects where metrics and related quantities are invariant to affine and projective groups. Highlighting two possibilities for representing object boundaries-ordered points (or landmarks) and parameterized curves-we study different combinations of these representations (points and curves) and transformations (affine and projective). Specifically, we provide solutions to three out of four situations and develop algorithms for computing geodesics and intrinsic sample statistics, leading up to Gaussian-type statistical models, and classifying test shapes using such models learned from training data. In the case of parameterized curves, we also achieve the desired goal of invariance to re-parameterizations. The geodesics are constructed by particularizing the path-straightening algorithm to geometries of current manifolds and are used, in turn, to compute shape statistics and Gaussian-type shape models. We demonstrate these ideas using a number of examples from shape and activity recognition.

Local uncontrollability for affine control systems with jumps

Science.gov (United States)

Treanţă, Savin

2017-09-01

This paper investigates affine control systems with jumps for which the ideal If(g1, …, gm) generated by the drift vector field f in the Lie algebra L(f, g1, …, gm) can be imbedded as a kernel of a linear first-order partial differential equation. It will lead us to uncontrollable affine control systems with jumps for which the corresponding reachable sets are included in explicitly described differentiable manifolds.

Phosphatidylserine and Phosphatidylethanolamine Bind to Protein Z Cooperatively and with Equal Affinity.

Directory of Open Access Journals (Sweden)

Tanusree Sengupta

Full Text Available Protein Z (PZ is an anticoagulant that binds with high affinity to Protein Z-dependent protease inhibitor (ZPI and accelerates the rate of ZPI-mediated inhibition of factor Xa (fXa by more than 1000-fold in the presence of Ca2+ and phospholipids. PZ promotion of the ZPI-fXa interaction results from the anchoring of the Gla domain of PZ onto phospholipid surfaces and positioning the bound ZPI in close proximity to the Gla-anchored fXa, forming a ternary complex of PZ/ZPI/fXa. Although interaction of PZ with phospholipid membrane appears to be absolutely crucial for its cofactor activity, little is known about the binding of different phospholipids to PZ. The present study was conceived to understand the interaction of different phospholipids with PZ. Experiments with both soluble lipids and model membranes revealed that PZ binds to phosphatidylserine (PS and phosphatidylethanolamine (PE with equal affinity (Kd~48 μM; further, PS and PE bound to PZ synergistically. Equilibrium dialysis experiments revealed two lipid-binding sites for both PS and PE. PZ binds with weaker affinity to other phospholipids, e.g., phosphatidic acid, phosphatidylglycerol, phosphatidylcholine and binding of these lipids is not synergistic with respect to PS. Both PS and PE -containing membranes supported the formation of a fXa-PZ complex. PZ protection of fXa from antithrombin inhibition were also shown to be comparable in presence of both PS: PC and PE: PC membranes. These findings are particularly important and intriguing since they suggest a special affinity of PZ, in vivo, towards activated platelets, the primary membrane involved in blood coagulation process.

An {Mathematical expression} iteration bound primal-dual cone affine scaling algorithm for linear programmingiteration bound primal-dual cone affine scaling algorithm for linear programming

NARCIS (Netherlands)

J.F. Sturm; J. Zhang (Shuzhong)

1996-01-01

textabstractIn this paper we introduce a primal-dual affine scaling method. The method uses a search-direction obtained by minimizing the duality gap over a linearly transformed conic section. This direction neither coincides with known primal-dual affine scaling directions (Jansen et al., 1993;

Characterization of a high affinity cocaine binding site in rat brain

International Nuclear Information System (INIS)

Calligaro, D.; Eldefrawi, M.

1986-01-01

Binding of [ 3 H]cocaine to synaptic membranes from whole rat brain was reversible and saturable. Nonlinear regression analysis of binding isotherms indicated two binding affinities: one with k/sub d/ = 16 nM, B/sub max/ = 0.65 pmoles/mg protein and the other with K/sub d/ = 660 nM, B/sub max/ = 5.1 pmoles/mg protein. The high-affinity binding of [ 3 H]cocaine was sensitive to the actions of trypsin and chymotrypsin but not carboxypeptidase, and was eliminated by exposure of the membranes to 95 0 C for 5 min. Specific binding at 2 nM was higher at pH 8.8 than at pH 7.0. Binding of [ 3 H]cocaine (15 nM) was inhibited by increasing concentrations of Na + ions. Several cocaine analogues, neurotransmitter uptake inhibitors and local anesthetics displaced specific [ 3 H]cocaine binding at 2 nM with various potencies. The cocaine analogue (-)-norcocaine was the most potent (IC 50 = 10 nM), while the local anesthetic tetracaine was the least potent in inhibiting [ 3 H]cocaine binding. Several biogenic amine uptake inhibitors, including tricyclic antidepressants and phencyclidine, had IC 50 values below μM concentrations

The topological entropy of iterated piecewise affine maps is uncomputable

Directory of Open Access Journals (Sweden)

Pascal Koiran

2001-12-01

Full Text Available We show that it is impossible to compute (or even to approximate the topological entropy of a continuous piecewise affine function in dimension four. The same result holds for saturated linear functions in unbounded dimension. We ask whether the topological entropy of a piecewise affine function is always a computable real number, and conversely whether every non-negative computable real number can be obtained as the topological entropy of a piecewise affine function. It seems that these two questions are also open for cellular automata.

Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux

NARCIS (Netherlands)

Bosdriesz, Evert; Wortel, Meike T.; Haanstra, Jurgen R.; Wagner, Marijke J.; De La Torre Cortés, Pilar; Teusink, Bas

2018-01-01

Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains unclear,

Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux

NARCIS (Netherlands)

Bosdriesz, Evert; Wortel, M.T.; Haanstra, Jurgen R.; Wagner, Marijke J.; De La Torre, P.; Teusink, Bas

2018-01-01

Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains

Discipline-Specific Compared to Generic Training of Teachers in Higher Education.

Science.gov (United States)

Silva-Fletcher, Ayona; May, Stephen A

A recurrent theme arising in the higher education sector is the suitability and effectiveness of generic versus discipline-specific training of university teachers, who are often recruited based on their disciplinary specialties to become teachers in higher education. We compared two groups of participants who had undergone training using a generic post-graduate certificate in higher education (PGCertGeneric) versus a discipline-specific course in veterinary education (PGCertVetEd). The study was conducted using a survey that allowed comparison of participants who completed PGCertGeneric (n=21) with PGCertVetEd (n=22). Results indicated that participants from both PGCertGeneric and PGCertVetEd considered teaching to be satisfying and important to their careers, valued the teaching observation component of the course, and identified similar training needs. However, the participants of the PGCertVetEd felt that the course made them better teachers, valued the relevance of the components taught, understood course design better, were encouraged to do further courses/reading in teaching and learning, changed their teaching as a result of the course, and were less stressed about teaching as compared to the PGCertGeneric participants (p<.05). It is likely that the PGCertVetEd, which was designed and developed by veterinarians with a wider understanding of the veterinary sector, helped the participants perceive the training course as suited to their needs.

Antibody affinity maturation

DEFF Research Database (Denmark)

Skjødt, Mette Louise

Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...... laboratory conditions. A particular emphasis was put on using molecular techniques in conjunction with microenvironmental measurements (O2, pH, irradiance), a combination that is rarely found but provides a much more detailed understanding of “cause and effect” in complex natural systems...

Accessibility of higher education: the right to higher education in comparative approach

OpenAIRE

Pūraitė, Aurelija

2011-01-01

At present there is an unprecedented demand for and a great diversification in higher education, as well as an increased awareness of its vital importance for socio-cultural and economic development. The complexity of the right to education is especially at issue while discussing the right to higher education, which on a national level is non-compulsory, even though the number of people who have acquired higher education during the second half of the twentieth century has tripled. Therefore t...

Higher genus partition functions of meromorphic conformal field theories

International Nuclear Information System (INIS)

Gaberdiel, Matthias R.; Volpato, Roberto

2009-01-01

It is shown that the higher genus vacuum amplitudes of a meromorphic conformal field theory determine the affine symmetry of the theory uniquely, and we give arguments that suggest that also the representation content with respect to this affine symmetry is specified, up to automorphisms of the finite Lie algebra. We illustrate our findings with the self-dual theories at c = 16 and c = 24; in particular, we give an elementary argument that shows that the vacuum amplitudes of the E 8 x E 8 theory and the Spin(32)/Z 2 theory differ at genus g = 5. The fact that the discrepancy only arises at rather high genus is a consequence of the modular properties of higher genus amplitudes at small central charges. In fact, we show that for c ≤ 24 the genus one partition function specifies already the partition functions up to g ≤ 4 uniquely. Finally we explain how our results generalise to non-meromorphic conformal field theories.

Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to intercellular adhesion molecule 1.

Science.gov (United States)

Muro, Silvia; Dziubla, Thomas; Qiu, Weining; Leferovich, John; Cui, Xiumin; Berk, Erik; Muzykantov, Vladimir R

2006-06-01

Targeting of diagnostic and therapeutic agents to endothelial cells (ECs) provides an avenue to improve treatment of many maladies. For example, intercellular adhesion molecule 1 (ICAM-1), a constitutive endothelial cell adhesion molecule up-regulated in many diseases, is a good determinant for endothelial targeting of therapeutic enzymes and polymer nanocarriers (PNCs) conjugated with anti-ICAM (anti-ICAM/PNCs). However, intrinsic and extrinsic factors that control targeting of anti-ICAM/PNCs to ECs (e.g., anti-ICAM affinity and PNC valency and flow) have not been defined. In this study we tested in vitro and in vivo parameters of targeting to ECs of anti-ICAM/PNCs consisting of either prototype polystyrene or biodegradable poly(lactic-coglycolic) acid polymers (approximately 200 nm diameter spheres carrying approximately 200 anti-ICAM molecules). Anti-ICAM/PNCs, but not control IgG/PNCs 1) rapidly (t1/2 approximately 5 min) and specifically bound to tumor necrosis factor-activated ECs in a dose-dependent manner (Bmax approximately 350 PNC/cell) at both static and physiological shear stress conditions and 2) bound to ECs and accumulated in the pulmonary vasculature after i.v. injection in mice. Anti-ICAM/PNCs displayed markedly higher EC affinity versus naked anti-ICAM (Kd approximately 80 pM versus approximately 8 nM) in cell culture and, probably because of this factor, higher value (185.3 +/- 24.2 versus 50.5 +/- 1.5% injected dose/g) and selectivity (lung/blood ratio 81.0 +/- 10.9 versus 2.1 +/- 0.02, in part due to faster blood clearance) of pulmonary targeting. These results 1) show that reformatting monomolecular anti-ICAM into high-affinity multivalent PNCs boosts their vascular immuno-targeting, which withstands physiological hydrodynamics and 2) support potential anti-ICAM/PNCs utility for medical applications.

Side-by-Side Comparison of Commonly Used Biomolecules That Differ in Size and Affinity on Tumor Uptake and Internalization

Science.gov (United States)

Leelawattanachai, Jeerapond; Kwon, Keon-Woo; Michael, Praveesuda; Ting, Richard; Kim, Ju-Young; Jin, Moonsoo M.

2015-01-01

The ability to use a systemically injected agent to image tumor is influenced by tumor characteristics such as permeability and vascularity, and the size, shape, and affinity of the imaging agent. In this study, six different imaging biomolecules, with or without specificity to tumor, were examined for tumor uptake and internalization at the whole body, ex-vivo tissue, and cellular levels: antibodies, antibody fragments (Fab), serum albumin, and streptavidin. The time of peak tumor uptake was dependent solely on the size of molecules, suggesting that molecular size is the major factor that influences tumor uptake by its effect on systemic clearance and diffusion into tumor. Affinity to tumor antigen failed to augment tumor uptake of Fab above non-specific accumulation, which suggests that Fab fragments of typical monoclonal antibodies may fall below an affinity threshold for use as molecular imaging agents. Despite abundant localization into the tumor, albumin and streptavidin were not found on cell surface or inside cells. By comparing biomolecules differing in size and affinity, our study highlights that while pharmacokinetics are a dominant factor in tumor uptake for biomolecules, affinity to tumor antigen is required for tumor binding and internalization. PMID:25901755

Affinity biosensors: techniques and protocols

National Research Council Canada - National Science Library

Rogers, Kim R; Mulchandani, Ashok

1998-01-01

..., and government to begin or expand their biosensors research. This volume, Methods in Biotechnology vol. 7: Affinity Biosensors: Techniques and Protocols, describes a variety of classical and emerging transduction technologies that have been interfaced to bioaffinity elements (e.g., antibodies and receptors). Some of the reas...

Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

Energy Technology Data Exchange (ETDEWEB)

Di Paolo, T.; Falardeau, P.

1987-08-31

The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p < 0.001). Competition for (/sup 3/H)-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-(..beta..-..gamma..-imino)triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables.

The affine quantum gravity programme

CERN Document Server

Klauder, J R

2002-01-01

The central principle of affine quantum gravity is securing and maintaining the strict positivity of the matrix left brace g-hat sub a sub b (x)right brace 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 sti...

Tumor affinity of radiolabeled peanut agglutinin compared with that of Ga-67 citrate in animal models

International Nuclear Information System (INIS)

Yokoyama, K.; Aburano, T.; Watanabe, N.; Kawabata, S.; Ishida, H.; Mukai, K.; Tonami, N.; Hisada, K.

1985-01-01

Peanut agglutinin (PNA) binds avidly to the immunodominant group of the tumor associated T antigen. The purpose of this study was to evaluate oncodiagnostic potential of radiolabeled PNA in animal models. PNA was labeled with I-125 or I-131 by Iodogen and also with In-111 by cyclic DTPA anhydride. The biological activity of PNA was examined by a hemaglutination titer with a photometer before and after labeling. Animal tumor models used were Lewis Lung Cancer(LLC), B-16 Melanotic Melanoma(MM), Yoshida Sarcoma(YS), Ehrlich Ascites Tumor(EAT and Hepatoma AH109A(HAH). Inflammatory tissue induced by turpentine oil was used as an abscess model. Serial scintigraphic images were obtained following IV injections of 100 μCi of I-131 or In-111-DTPA-PNA. The tumor affinity of Ga-67 citrate was studied to compare that of radiolabeled PNA. Tissue biodistribution was studied in EAT bearing mice. All of these tumor models except HAH were clearly visible by radiolabeled PNA without subtraction techniques. In the models of LLC and EAT, PNA showed the better accumulation into the tumor tissue than Ga-67 citrate. In YS and MM, PNA represented almost the same accumulation as Ga-67 citrate. The localization of PNA into abscess tissue wasn't found although Ga-67 citrate markedly accumulated into abscess tissue as well as tumor tissue. The clearance of PNA from tumor was slower than those from any other organs. Tumor to muscle ratio was 5.1 at 48hrs. and tumor to blood ratio increased with time to 2.3 at 96hrs. These results suggested that radiolabeled PNA may have a potential in the detection of tumor

Affinity resins as new tools for identifying target proteins of ascorbic acid.

Science.gov (United States)

Iwaoka, Yuji; Nishino, Kohei; Ishikawa, Takahiro; Ito, Hideyuki; Sawa, Yoshihiro; Tai, Akihiro

2018-02-12

l-Ascorbic acid (AA) has diverse physiological functions, but little is known about the functional mechanisms of AA. In this study, we synthesized two types of affinity resin on which AA is immobilized in a stable form to identify new AA-targeted proteins, which can provide important clues for elucidating unknown functional mechanisms of AA. To our knowledge, an affinity resin on which AA as a ligand is immobilized has not been prepared, because AA is very unstable and rapidly degraded in an aqueous solution. By using the affinity resins, cytochrome c (cyt c) was identified as an AA-targeted protein, and we showed that oxidized cyt c exhibits specific affinity for AA. These results suggest that two kinds of AA-affinity resin can be powerful tools to identify new target proteins of AA.

Synthesis, Biodistribution and In vitro Evaluation of Brain Permeable High Affinity Type 2 Cannabinoid Receptor Agonists [11C]MA2 and [18F]MA3.

Science.gov (United States)

Ahamed, Muneer; van Veghel, Daisy; Ullmer, Christoph; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy M

2016-01-01

The type 2 cannabinoid receptor (CB2) is a member of the endocannabinoid system and is known for its important role in (neuro)inflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([ 11 C]MA2) and a fluorine-18 ([ 18 F]MA3) labeled analog of a highly potent N -arylamide oxadiazole CB2 agonist (EC 50 = 0.015 nM). MA2 and MA3 behaved as potent CB2 agonist (EC 50 : 3 nM and 0.1 nM, respectively) and their in vitro binding affinity for h CB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group) was found to have higher binding affinity and EC 50 values when compared to the originally reported trifluoromethyl analog 12 . [ 11 C]MA2 and [ 18 F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [ 11 C]MA2 and [ 18 F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However, in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted.

In Defence of International Comparative Studies. on the Analytical and Explanatory Power of the Nation State in International Comparative Higher Education Research

Science.gov (United States)

Kosmützky, Anna

2015-01-01

Higher education is undergoing a process of globalization and new realities of a globalized higher education world are emerging. Globalization also has a profound impact on higher education research. Global and transnational topics are theoretically and empirically elaborated and seem on the rise, whereas the international comparative outlook…

Membrane Affinity of Platensimycin and Its Dialkylamine Analogs

Directory of Open Access Journals (Sweden)

Ian Rowe

2015-08-01

Full Text Available Membrane permeability is a desired property in drug design, but there have been difficulties in quantifying the direct drug partitioning into native membranes. Platensimycin (PL is a new promising antibiotic whose biosynthetic production is costly. Six dialkylamine analogs of PL were synthesized with identical pharmacophores but different side chains; five of them were found inactive. To address the possibility that their activity is limited by the permeation step, we calculated polarity, measured surface activity and the ability to insert into the phospholipid monolayers. The partitioning of PL and the analogs into the cytoplasmic membrane of E. coli was assessed by activation curve shifts of a re-engineered mechanosensitive channel, MscS, in patch-clamp experiments. Despite predicted differences in polarity, the affinities to lipid monolayers and native membranes were comparable for most of the analogs. For PL and the di-myrtenyl analog QD-11, both carrying bulky sidechains, the affinity for the native membrane was lower than for monolayers (half-membranes, signifying that intercalation must overcome the lateral pressure of the bilayer. We conclude that the biological activity among the studied PL analogs is unlikely to be limited by their membrane permeability. We also discuss the capacity of endogenous tension-activated channels to detect asymmetric partitioning of exogenous substances into the native bacterial membrane and the different contributions to the thermodynamic force which drives permeation.

Online identification of continuous bimodal and trimodal piecewise affine systems

NARCIS (Netherlands)

Le, Q.T.; van den Boom, A.J.J.; Baldi, S.; Rantzer, Anders; Bagterp Jørgensen, John; Stoustrup, Jakob

2016-01-01

This paper investigates the identification of continuous piecewise affine systems in state space form with jointly unknown partition and subsystem matrices. The partition of the system is generated by the so-called centers. By representing continuous piecewise affine systems in the max-form and

Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

Energy Technology Data Exchange (ETDEWEB)

Ross, Ryan D. [Rush University Medical Center, Department of Anatomy and Cell Biology (United States); Cole, Lisa E.; Roeder, Ryan K., E-mail: rroeder@nd.edu [University of Notre Dame, Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program (United States)

2012-10-15

Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate (l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

Gender Inequalities and Higher Music Education: Comparing the UK and Sweden

Science.gov (United States)

de Boise, Sam

2018-01-01

Whilst the impact of gender inequalities has been studied in relation to music education, especially in the UK, relatively little has been written about their impact on higher music education (HME). This article compares data on HME programs and courses, in the UK and Sweden, from 2010 to 2014. It looks at similarities and differences in the…

Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype

DEFF Research Database (Denmark)

Jorgensen, Rasmus; Martini, Lene; Schwartz, Thue W

2005-01-01

To dissect the interaction between beta-arrestin ((beta)arr) and family B G protein-coupled receptors, we constructed fusion proteins between the glucagon-like peptide 1 receptor and (beta)arr2. The fusion constructs had an increase in apparent affinity selectively for glucagon, suggesting...... that (beta)arr2 interaction locks the receptor in a high-affinity conformation, which can be explored by some, but not all, ligands. The fusion constructs adopted a signaling phenotype governed by the tethered (beta)arr2 with an attenuated G protein-mediated cAMP signal and a higher maximal internalization...... of that which has previously been characterized for family A G protein-coupled receptors, suggesting similarities in the effect of (beta)arr interaction between family A and B receptors also at the molecular level....

[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.

Fluorescence and computational studies of thymidine phosphorylase affinity toward lipidated 5-FU derivatives

Science.gov (United States)

Lettieri, R.; D'Abramo, M.; Stella, L.; La Bella, A.; Leonelli, F.; Giansanti, L.; Venanzi, M.; Gatto, E.

2018-04-01

Thymidine phosphorylase (TP) is an enzyme that is up-regulated in a wide variety of solid tumors, including breast and colorectal cancers. It is involved in tumor growth and metastasis, for this reason it is one of the key enzyme to be inhibited, in an attempt to prevent tumor proliferation. However, it also plays an active role in cancer treatment, through its contribution in the conversion of the anti-cancer drug 5-fluorouracil (5-FU) to an irreversible inhibitor of thymidylate synthase (TS), responsible of the inhibition of the DNA synthesis. In this work, the intrinsic TP fluorescence has been investigated for the first time and exploited to study TP binding affinity for the unsubstituted 5-FU and for two 5-FU derivatives, designed to expose this molecule on liposomal membranes. These molecules were obtained by functionalizing the nitrogen atom with a chain consisting of six (1) or seven (2) units of glycol, linked to an alkyl moiety of 12 carbon atoms. Derivatives (1) and (2) exhibited an affinity for TP in the micromolar range, 10 times higher than the parent compound, irrespective of the length of the polyoxyethylenic spacer. This high affinity was maintained also when the compounds were anchored in liposomal membranes. Experimental results were supported by molecular dynamics simulations and docking calculations, supporting a feasible application of the designed supramolecular lipid structure in selective targeting of TP, to be potentially used as a drug delivery system or sensor device.

Biochemical method for fast affinity diagnosis in grape-vine transplantation

International Nuclear Information System (INIS)

Lilov, D.

1977-01-01

Long term experiments have proved the affinity of cv. Mavroud in transplantations on various root stocks. Best affinity was observed in the combination cv. Mavroud X Riparia tomanteau, followed, in a descending order, by the combinations Mavroud X Mavroud (autotransplantation), Mavroud X Berlandieri X Riparia Kobber SBB and Mavroud X Riparia 33 EM. In view to establish indices for predicting the transplantation affinity a great number of physiological-biochemical and morphological-anatomical studies were carried out. The results obtained showed that a most clearly expressed positive, statistically significant correlation exists between the amount of 15 N transported from the root stock to the scions, shoots and leaves. As a result, a biochemical method for fast affinity diagnosis in grape-vine transplantation has been developed. The reliability of the method has been checked up also with other cultivars. Up to the present no such method was known in grape-vine science and practice. (author)

Methods for quantifying T cell receptor binding affinities and thermodynamics

Science.gov (United States)

Piepenbrink, Kurt H.; Gloor, Brian E.; Armstrong, Kathryn M.; Baker, Brian M.

2013-01-01

αβ T cell receptors (TCRs) recognize peptide antigens bound and presented by class I or class II major histocompatibility complex (MHC) proteins. Recognition of a peptide/MHC complex is required for initiation and propagation of a cellular immune response, as well as the development and maintenance of the T cell repertoire. Here we discuss methods to quantify the affinities and thermodynamics of interactions between soluble ectodomains of TCRs and their peptide/MHC ligands, focusing on titration calorimetry, surface plasmon resonance, and fluorescence anisotropy. As TCRs typically bind ligand with weak-to-moderate affinities, we focus the discussion on means to enhance the accuracy and precision of low affinity measurements. In addition to further elucidating the biology of the T cell mediated immune response, more reliable low affinity measurements will aid with more probing studies with mutants or altered peptides that can help illuminate the physical underpinnings of how TCRs achieve their remarkable recognition properties. PMID:21609868

Affinity purification using recombinant PXR as a tool to characterize environmental ligands.

Science.gov (United States)

Dagnino, Sonia; Bellet, Virginie; Grimaldi, Marina; Riu, Anne; Aït-Aïssa, Sélim; Cavaillès, Vincent; Fenet, Hélène; Balaguer, Patrick

2014-02-01

Many environmental endocrine disrupting compounds act as ligands for nuclear receptors. The human pregnane X receptor (hPXR), for instance, is activated by a variety of environmental ligands such as steroids, pharmaceutical drugs, pesticides, alkylphenols, polychlorinated biphenyls and polybromo diethylethers. Some of us have previously reported the occurrence of hPXR ligands in environmental samples but failed to identify them. The aim of this study was to test whether a PXR-affinity column, in which recombinant hPXR was immobilized on solid support, could help the purification of these chemicals. Using PXR ligands of different affinity (10 nM < EC50 < 10 μM), we demonstrated that the PXR-affinity preferentially column captured ligands with medium to high affinities (EC50 < 1 μM). Furthermore, by using the PXR-affinity column to analyze an environmental sample containing ERα, AhR, AR, and PXR activities, we show that (i) half of the PXR activity of the sample was due to compounds with medium to high affinity for PXR and (ii) PXR shared ligands with ERα, AR, and AhR. These findings demonstrate that the newly developed PXR-affinity column coupled to reporter cell lines represents a valuable tool for the characterization of the nature of PXR active compounds and should therefore guide and facilitate their further analysis. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites.

Science.gov (United States)

Erspamer, V; Melchiorri, P; Falconieri-Erspamer, G; Negri, L; Corsi, R; Severini, C; Barra, D; Simmaco, M; Kreil, G

1989-07-01

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid binding sites than any other natural compound known. Two deltorphins with the sequence Tyr-Ala-Phe-Asp(or Glu)-Val-Val-Gly-NH2 have been isolated from skin extracts of Phyllomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, [D-Ala2]deltorphins I and II, show an even higher affinity for delta receptors than the previously characterized deltorphin, which contains D-methionine as the second amino acid. These peptides show some similarity to another constituent of Phyllomedusa skin, dermorphin, which is highly selective for mu-opioid receptors. These peptides all have the N-terminal sequence Tyr-D-Xaa-Phe, where D-Xaa is either D-alanine or D-methionine. While this structure seems to be capable of activating both mu and delta opioid receptors, differences in the C-terminal regions of these peptides are probably responsible for the observed high receptor selectivity of dermorphin and deltorphin.

Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites.

OpenAIRE

Erspamer, V; Melchiorri, P; Falconieri-Erspamer, G; Negri, L; Corsi, R; Severini, C; Barra, D; Simmaco, M; Kreil, G

1989-01-01

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid binding sites than any other natural compound known. Two deltorphins with the sequence Tyr-Ala-Phe-Asp(or Glu)-Val-Val-Gly-NH2 have been isolated from skin extracts of Phyllomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, [D-Ala2]deltorphins I and II, show an even higher affi...

Novel trends in affinity biosensors: current challenges and perspectives

International Nuclear Information System (INIS)

Arugula, Mary A; Simonian, Aleksandr

2014-01-01

Molecular biorecognition processes facilitate physical and biochemical interactions between molecules in all crucial metabolic pathways. Perhaps the target analyte and the biorecognition element interactions have the most impactful use in biosensing applications. Traditional analytical sensing systems offer excellent biorecognition elements with the ability to detect and determine the presence of analytes. High affinity antibodies and DNA play an important role in the development of affinity biosensors based on electrochemical, optical and mass sensitive approaches. Advancements in this area routinely employ labels, label free, nanoparticles, multifunctional matrices, carbon nanotubes and other methods to meet the requirements of its own application. However, despite increasing affinity ceilings for conventional biosensors, the field draws back in meeting specifically important demands, such as long-term stability, ultrasensitivity, rapid detection, extreme selectivity, strong biological base, calibration, in vivo measurements, regeneration, satisfactory performance and ease of production. Nevertheless, recent efforts through this line have produced novel high-tech nanosensing systems such as ‘aptamers’ and ‘phages’ which exhibit high-throughput sensing. Aptamers and phages are powerful tools that excel over antibodies in sensibility, stability, multi-detection, in vivo measurements and regeneration. Phages are superior in stability, screening for affinity-based target molecules ranging from small to proteins and even cells, and easy production. In this review, we focus mainly on recent developments in affinity-based biosensors such as immunosensors, DNA sensors, emphasizing aptasensors and phage-based biosensors basing on novel electrochemical, optical and mass sensitive detection techniques. We also address enzyme inhibition-based biosensors and the current problems associated with the above sensors and their future perspectives. (topical review)

Water-Hydrogel Binding Affinity Modulates Freeze-Drying-Induced Micropore Architecture and Skeletal Myotube Formation.

Science.gov (United States)

Rich, Max H; Lee, Min Kyung; Marshall, Nicholas; Clay, Nicholas; Chen, Jinrong; Mahmassani, Ziad; Boppart, Marni; Kong, Hyunjoon

2015-08-10

Freeze-dried hydrogels are increasingly used to create 3D interconnected micropores that facilitate biomolecular and cellular transports. However, freeze-drying is often plagued by variance in micropore architecture based on polymer choice. We hypothesized that water-polymer binding affinity plays a significant role in sizes and numbers of micropores formed through freeze-drying, influencing cell-derived tissue quality. Poly(ethylene glycol)diacrylate (PEGDA) hydrogels with alginate methacrylate (AM) were used due to AM's higher binding affinity for water than PEGDA. PEGDA-AM hydrogels with larger AM concentrations resulted in larger sizes and numbers of micropores than pure PEGDA hydrogels, attributed to the increased mass of water binding to the PEGDA-AM gel. Skeletal myoblasts loaded in microporous PEGDA-AM hydrogels were active to produce 3D muscle-like tissue, while those loaded in pure PEGDA gels were localized on the gel surface. We propose that this study will be broadly useful in designing and improving the performance of various microporous gels.

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

OpenAIRE

de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

2016-01-01

Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screen...

Affinity of 169Yb, 67Ga and 111In for malignant tumor, (1)

International Nuclear Information System (INIS)

Ando, Itsuko

1975-01-01

The tumor affinity of 169 Yb-citrate, 67 Ga-citrate and 111 In-citrate was examined by using Yoshida sarcoma-bearing rats, and the affinity of these compounds for inflammation was also tested using rats with inflammation induced by croton oil injection. In this investigation there was no great difference in uptake by the tumor tissue of these compounds, but a great difference was observed in the retention value of the blood and uptake rate in the bone. 169 Yb-citrate was cleared rapidly from the blood and was taken mostly into the bone. So the retention values in the soft tissues became very small. On the other hand, 111 In-citrate was slowly and only slightly taken into the bone from the blood, so the retention values in the soft tissue remained relatively high. 67 Ga-citrate showed the intermediate value between the bone uptake rate of 169 Yb-citrate and that of 111 In-citrate. In the following experiments, 169 Yb-citrate and 67 Ga-citrate were compared in four strains: Yoshida sarcoma, Walker carcinosarcoma 256, Sarcoma 180, and Ehrlich tumor. The uptake rate of 169 Yb in tumor tissue was much larger than that of 67 Ga in Ehrlich tumor-bearing mice, but the value of 169 Yb was slightly smaller than those of 67 Ga in Yoshida sarcoma-bearing rats, Walker carcinosarcoma 256-bearing rats and Sarcoma 180-bearing mice. Tumor to organ ratios of 169 Yb, which were most important for tumor scanning, were much larger than those of 67 Ga in all four strains except tumor to bone ratios of 169 Yb. From the above-described facts, it was shown that 169 Yb-citrate had a stronger tumor affinity than 67 Ga-citrate and that the tumor affinity of 169 Yb-citrate was similar in these four strains of tumor bearing animals. These three compounds had a relatively strong affinity with the inflammatory tissue. (auth.)

Application of radiation grafted media for lectin affinity separation and urease immobilization: a novel approach to tumor therapy and renal disease diagnosis

International Nuclear Information System (INIS)

Mueller-Schulte, D.; Daschek, W.

1995-01-01

Carriers modified by synergistic radiation grafting are used as affinity media for the separation of a lectin from a mistletoe extract. The grafted supports show distinctly superior properties when compared to conventional affinity media. The application of these carriers as urease immobilization support incorporated in a conductimetric bioreactor for urea analysis as potential diagnostic device in renal diseases is also described. (Author)

Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification

Directory of Open Access Journals (Sweden)

Jeliazko R. Jeliazkov

2018-03-01

Full Text Available Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody’s antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity.

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.

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.

APPLICATION OF IMMUNOGLOBULIN-BINDING PROTEINS A, G, L IN THE AFFINITY CHROMATOGRAPHY

Directory of Open Access Journals (Sweden)

О. V. Sviatenko

2014-04-01

Full Text Available Proteins A, G and L are native or recombinant proteins of microbial origin that bind to mammalian immunoglobulins. Preferably recombinant variants of proteins A, G, L are used in biotechnology for affinity sorbents production. Сomparative characteristics of proteins A, G, L and affinity sorbents on the basis of them, advantages and disadvantages of these proteins application as ligands in the affinity chromatography are done. Analysis of proteins A, G, L properties is presented. Binding specificities and affinities of these proteins differ between species and antibody subclass. Protein А has high affinity to human IgG1, IgG2, IgG4, mouse IgG2a, IgG2b, IgG3, goat and sheep IgG2, dog, cat, guinea pig, rabbit IgG. Protein G binds strongly to human, mouse, cow, goat, sheep and rabbit IgG. Protein L has ability of strong binding to immunoglobulin kappa-chains of human, mouse, rat and pig. Expediency of application of affinity chromatography with usage of sorbents on the basis of immobilized proteins A, G, L are shown for isolation and purification of antibodies different classes. Previously mentioned method is used as an alternative to conventional methods of protein purification, such as ion-exchange, hydrophobic interactions, metal affinity chromatography, ethanol precipitation due to simplicity in usage, possibility of one-step purification process, obtaining of proteins high level purity, multiuse at maintenance of proper storage and usage conditions. Affinity sorbents on the basis of immobilized proteins A, G, L are used not only for antibodies purification, but also for extraction of different antibodies fractions from blood serum.

Learning in a Game-Based Virtual Environment: A Comparative Evaluation in Higher Education

Science.gov (United States)

Mayer, Igor; Warmelink, Harald; Bekebrede, Geertje

2013-01-01

The authors define the requirements and a conceptual model for comparative evaluation research of simulation games and serious games (SGs) in a learning context. A first operationalisation of the model was used to comparatively evaluate a suite of 14 SGs on varying topics played between 2004 and 2009 in 13 institutes of higher education in the…

Bioinorganic Chemistry of Parkinson's Disease: Affinity and Structural Features of Cu(I) Binding to the Full-Length β-Synuclein Protein.

Science.gov (United States)

Miotto, Marco C; Pavese, Mayra D; Quintanar, Liliana; Zweckstetter, Markus; Griesinger, Christian; Fernández, Claudio O

2017-09-05

Alterations in the levels of copper in brain tissue and formation of α-synuclein (αS)-copper complexes might play a key role in the amyloid aggregation of αS and the onset of Parkinson's disease (PD). Recently, we demonstrated that formation of the high-affinity Cu(I) complex with the N-terminally acetylated form of the protein αS substantially increases and stabilizes local conformations with α-helical secondary structure and restricted motility. In this work, we performed a detailed NMR-based structural characterization of the Cu(I) complexes with the full-length acetylated form of its homologue β-synuclein (βS), which is colocalized with αS in vivo and can bind copper ions. Our results show that, similarly to αS, the N-terminal region of βS constitutes the preferential binding interface for Cu(I) ions, encompassing two independent and noninteractive Cu(I) binding sites. According to these results, βS binds the metal ion with higher affinity than αS, in a coordination environment that involves the participation of Met-1, Met-5, and Met-10 residues (site 1). Compared to αS, the shift of His from position 50 to 65 in the N-terminal region of βS does not change the Cu(I) affinity features at that site (site 2). Interestingly, the formation of the high-affinity βS-Cu(I) complex at site 1 in the N-terminus promotes a short α-helix conformation that is restricted to the 1-5 segment of the AcβS sequence, which differs with the substantial increase in α-helix conformations seen for N-terminally acetylated αS upon Cu(I) complexation. Our NMR data demonstrate conclusively that the differences observed in the conformational transitions triggered by Cu(I) binding to AcαS and AcβS find a correlation at the level of their backbone dynamic properties; added to the potential biological implications of these findings, this fact opens new avenues of investigations into the bioinorganic chemistry of PD.

Molecular Affinity of Mabolo Extracts to an Octopamine Receptor of a Fruit Fly

Directory of Open Access Journals (Sweden)

Francoise Neil D. Dacanay

2017-10-01

Full Text Available Essential oils extracted from plants are composed of volatile organic compounds that can affect insect behavior. Identifying the active components of the essential oils to their biochemical target is necessary to design novel biopesticides. In this study, essential oils extracted from Diospyros discolor (Willd. were analyzed using gas chromatography mass spectroscopy (GC-MS to create an untargeted metabolite profile. Subsequently, a conformational ensemble of the Drosophila melanogaster octopamine receptor in mushroom bodies (OAMB was created from a molecular dynamics simulation to resemble a flexible receptor for docking studies. GC-MS analysis revealed the presence of several metabolites, i.e. mostly aromatic esters. Interestingly, these aromatic esters were found to exhibit relatively higher binding affinities to OAMB than the receptor’s natural agonist, octopamine. The molecular origin of this observed enhanced affinity is the π -stacking interaction between the aromatic moieties of the residues and ligands. This strategy, computational inspection in tandem with untargeted metabolomics, may provide insights in screening the essential oils as potential OAMB inhibitors.

Schubert calculus and threshold polynomials of affine fusion

International Nuclear Information System (INIS)

Irvine, S.E.; Walton, M.A.

2000-01-01

We show how the threshold level of affine fusion, the fusion of Wess-Zumino-Witten (WZW) conformal field theories, fits into the Schubert calculus introduced by Gepner. The Pieri rule can be modified in a simple way to include the threshold level, so that calculations may be done for all (non-negative integer) levels at once. With the usual Giambelli formula, the modified Pieri formula deforms the tensor product coefficients (and the fusion coefficients) into what we call threshold polynomials. We compare them with the q-deformed tensor product coefficients and fusion coefficients that are related to q-deformed weight multiplicities. We also discuss the meaning of the threshold level in the context of paths on graphs

Experimental and theoretical binding affinity between polyvinylpolypyrrolidone and selected phenolic compounds from food matrices.

Science.gov (United States)

Durán-Lara, Esteban F; López-Cortés, Xaviera A; Castro, Ricardo I; Avila-Salas, Fabián; González-Nilo, Fernando D; Laurie, V Felipe; Santos, Leonardo S

2015-02-01

Polyvinylpolypyrrolidone (PVPP) is a fining agent, widely used in winemaking and brewing, whose mode of action in removing phenolic compounds has not been fully characterised. The aim of this study was to evaluate the experimental and theoretical binding affinity of PVPP towards six phenolic compounds representing different types of phenolic species. The interaction between PVPP and phenolics was evaluated in model solutions, where hydroxyl groups, hydrophobic bonding and steric hindrance were characterised. The results of the study indicated that PVPP exhibits high affinity for quercetin and catechin, moderate affinity for epicatechin, gallic acid and lower affinity for 4-methylcatechol and caffeic acid. The affinity has a direct correlation with the hydroxylation degree of each compound. The results show that the affinity of PVPP towards phenols is related with frontier orbitals. This work demonstrates a direct correlation between the experimental affinity and the interaction energy calculations obtained through computational chemistry methods. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of 2,3-diphosphoglycerate on oxygen affinity of blood in sickle cell anemia

Science.gov (United States)

Charache, Samuel; Grisolia, Santiago; Fiedler, Adam J.; Hellegers, Andre E.

1970-01-01

Blood of patients with sickle cell anemia (SS) exhibits decreased affinity for oxygen, although the oxygen affinity of hemoglobin S is the same as that of hemoglobin A. SS red cells contain more 2,3-diphosphoglycerate (DPG) than normal erythrocytes. The oxygen affinity of hemolyzed red cells is decreased by added DPG, and hemolysates prepared from SS red cells do not differ from normal hemolysates in this regard. Reduction of oxygen affinity to the levels found in intact SS red cells required DPG concentrations in excess of those found in most SS patients. The same was true of oxygen affinity of patients with pyruvate kinase deficiency. Other organic phosphates, as well as inorganic ions, are known to alter the oxygen affinity of dilute solutions of hemoglobin. These substances, the state of aggregation of hemoglobin molecules, and cytoarchitectural factors probably play roles in determining oxygen affinity of both normal and SS red cells. PMID:5443181

On the Lp affine isoperimetric inequalities

Indian Academy of Sciences (India)

surface area measure on convex bodies. We also establish the reverse version of -Petty projection inequality and an affine isoperimetric inequality of − p K . Author Affiliations. Wuyang Yu1 Gangsong Leng2. Institute of Management Decision ...

Characterization of high affinity [3H]triazolam binding in rat brain

International Nuclear Information System (INIS)

Earle, M.; Concas, A.; Yamamura, H.I.

1986-01-01

The hypnotic Triazolam (TZ), a triazolo (1,4)-benzodiazepine, displays a short physiological half life and has been used for the treatment of insomnia related to anxiety states. Specific binding properties of this recently tritiated TZ were characterized. The authors major objectives were the direct measurement of the temperature dependence and the GABA effect on [ 3 H]TZ binding. Saturation studies showed a shift to lower affinity at 37 0 C (K/sub d/ = 0.25 +/- 0.01 nM at O 0 C; K/sub d/ = 1.46 +/- 0.03 nM at 37 0 C) while the B/sub max/ values remained unchanged (1003 +/- 37 fmoles/mg prot. at 0 0 C and 1001 +/- 43 fmoles/mg prot. at 37 0 C). Inhibition studies showed that [ 3 H]TZ binding displayed no GABA shift at 0 0 C(K/sub i/ 0.37 +/- 0.03 nM/- GABA and K/sub i/ = 0.55 +/- 0.13 nM/+GABA) but a nearly two-fold shift was apparent at 37 0 C (K/sub i/ = 2.92 +/- 0.2 nM/-GABA; K/sub i/ = 1.37 +/- 0.11 mM/+GABA). These results were also confirmed by saturation studies in the presence or absence of GABA showing a shift to higher affinity in the presence of GABA only at 37 0 C. In Ro 15-1788/[ 3 H]TZ competition experiments the presence of GABA did not affect the inhibitory potency of Ro 15-1788 on [ 3 H]TZ binding at both temperatures. In conclusion [ 3 H]TZ binding showed an extremely high affinity for benzodiazepine receptors. In contrast to reported literature, the findings suggest that TZ interacts with benzodiazepine receptors similar to other benzodiazepine agonists

Purification of camel liver catalase by zinc chelate affinity chromatography and pH gradient elution: An enzyme with interesting properties.

Science.gov (United States)

Chafik, Abdelbasset; Essamadi, Abdelkhalid; Çelik, Safinur Yildirim; Mavi, Ahmet

2017-12-01

Climate change and increasing temperatures are global concerns. Camel (Camelus dromedarius) lives most of its life under high environmental stress in the desert and represent ideal model for studying desert adaptation among mammals. Catalase plays a key role in protecting cells against oxidative stress. For the first time, catalase from camel liver was purified to homogeneity by zinc chelate affinity chromatography using pH gradient elution, a better separation was obtained. A purification fold of 201.81 with 1.17% yield and a high specific activity of 1132539.37U/mg were obtained. The native enzyme had a molecular weight of 268kDa and was composed of four subunits of equal size (65kDa). The enzyme showed optimal activity at a temperature of 45°C and pH 7.2. Thiol reagents, β-Mercaptoethanol and D,L-Dithiothreitol, inhibited the enzyme activity. The enzyme was inhibited by Al 3+ , Cd 2+ and Mg 2+ , whereas Ca 2+ , Co 2+ and Ni 2+ stimulated the catalase activity. Reduced glutathione has no effect on catalase activity. The K m and V max of the enzyme for hydrogen peroxide were 37.31mM and 6185157U/mg, respectively. Sodium azide inhibited the enzyme noncompetitively with K i value of 14.43μM, the IC 50 was found to be 16.71μM. The properties of camel catalase were different comparing to those of mammalian species. Relatively higher molecular weight, higher optimum temperature, protection of reduced glutathione from hydrogen peroxide oxidation and higher affinity for hydrogen peroxide and sodium azide, these could be explained by the fact that camel is able to live in the intense environmental stress in the desert. Copyright © 2017 Elsevier B.V. All rights reserved.

The spectrum of the conserved charges in affine Toda theories

International Nuclear Information System (INIS)

Niedermaier, M.R.

1992-07-01

A vertex operator construction for the phase of the minimal form factor is used to predict the exact spectrum of the infinite set of conserved charges on the multi-particle states in affine Toda theories from the bootstrap S-matrix. Conversely, the scattering phase can be recovered from the spectral information. The result is checed against the classical spectrum which is calculated ab-initio using the τ-function formalism. The latter is shown to provide a considerable shortcut compared to the traditional use of the inverse scattering transform. (orig.)

Specificity and affinity quantification of flexible recognition from underlying energy landscape topography.

Directory of Open Access Journals (Sweden)

Xiakun Chu

2014-08-01

Full Text Available Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less flexibility leads to weaker (stronger coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition.

Comparative VOCs sensing performance for conducting polymer and porphyrin functionalized carbon nanotubes based sensors

Science.gov (United States)

Datta, Kunal; Rushi, Arti; Ghosh, Prasanta; Shirsat, Mahendra

2018-05-01

We report sensors for detection of ethyl alcohol, a prominent volatile organic compound (VOC). Single walled carbon nanotubes were selected as main sensing backbone. As efficiency of sensor is dependent upon the choice of sensing materials, the performances of conducting polymer and porphyrin based sensors were compared. Chemiresistive sensing modality was adopted to observe the performance of sensors. It has been found that porphyrin based sensor shows higher affinity towards ethyl alcohol.

Dental affinities of the C-group inhabitants of Hierakonpolis, Egypt: Nubian, Egyptian, or both?

Science.gov (United States)

Irish, J D; Friedman, R

2010-04-01

By c. 2050 BC a small community of C-Group Nubians was present deep within Egyptian territory at the city of Hierakonpolis. Their descendants stayed for the next 400 years. Today, the site of Hierakonpolis, 113 km north of Aswan, is known for its Egyptian deposits; however, it also contains a C-Group cemetery, which documents the northernmost occurrence of this culture. Sixty skeletons were excavated. Tombs feature Nubian architecture and goods, including leather garments, although the use of Egyptian mortuary practices and artifacts increased through time. Dates range from the early 11th Dynasty into the Second Intermediate period. During this time the Egyptian empire occupied Lower Nubia, and their state ideology vilified Nubians. Yet, at least in death, the C-Group inhabitants of Hierakonpolis proudly displayed their cultural heritage. Beyond discerning the reason(s) for their presence at the site (e.g., mercenaries, leather-workers, entertainers?), the focus of this report is to estimate their biological affinity. Were they akin to other Nubians, Egyptians, or both? And, was increasing 'Egyptianization' evident in the mortuary ritual accompanied by concomitant genetic influence? To address these queries, up to 36 dental morphological traits in the recovered individuals were compared to those in 26 regional comparative samples. The most influential traits were identified and phenetic affinities were calculated using the mean measure of divergence and other multivariate analyses. Assuming phenetic similarity provides an estimate of genetic relatedness, these affinities suggest the individuals comprising the C-Group sample were, and remained Nubian during their tenure at Hierakonpolis. Copyright 2010 Elsevier GmbH. All rights reserved.

Computational modeling and molecular imprinting for the development of acrylic polymers with high affinity for bile salts.

Science.gov (United States)

Yañez, Fernando; Chianella, Iva; Piletsky, Sergey A; Concheiro, Angel; Alvarez-Lorenzo, Carmen

2010-02-05

This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow

Affinity functions for modeling glass dissolution rates

Energy Technology Data Exchange (ETDEWEB)

Bourcier, W.L. [Lawrence Livermore National Lab., CA (United States)

1997-07-01

Glass dissolution rates decrease dramatically as glass approach ''saturation'' with respect to the leachate solution. Most repository sites are chosen where water fluxes are minimal, and therefore the waste glass is most likely to dissolve under conditions close to ''saturation''. The key term in the rate expression used to predict glass dissolution rates close to ''saturation'' is the affinity term, which accounts for saturation effects on dissolution rates. Interpretations of recent experimental data on the dissolution behaviour of silicate glasses and silicate minerals indicate the following: 1) simple affinity control does not explain the observed dissolution rate for silicate minerals or glasses; 2) dissolution rates can be significantly modified by dissolved cations even under conditions far from saturation where the affinity term is near unity; 3) the effects of dissolved species such as Al and Si on the dissolution rate vary with pH, temperature, and saturation state; and 4) as temperature is increased, the effect of both pH and temperature on glass and mineral dissolution rates decrease, which strongly suggests a switch in rate control from surface reaction-based to diffusion control. Borosilicate glass dissolution models need to be upgraded to account for these recent experimental observations. (A.C.)

On $L_p$ Affine Surface Area and Curvature Measures

OpenAIRE

Zhao, Yiming

2015-01-01

The relationship between $L_p$ affine surface area and curvature measures is investigated. As a result, a new representation of the existing notion of $L_p$ affine surface area depending only on curvature measures is derived. Direct proofs of the equivalence between this new representation and those previously known are provided. The proofs show that the new representation is, in a sense, "polar" to that of Lutwak's and "dual" to that of Sch\\"utt & Werner's.

F+ and F⁻ affinities of simple N(x)F(y) and O(x)F(y) compounds.

Science.gov (United States)

Grant, Daniel J; Wang, Tsang-Hsiu; Vasiliu, Monica; Dixon, David A; Christe, Karl O

2011-03-07

Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted for the neutral and ionic N(x)F(y) and O(x)F(y) systems using coupled cluster theory with single and double excitations and including a perturbative triples correction (CCSD(T)) method with correlation consistent basis sets extrapolated to the complete basis set (CBS) limit. To achieve near chemical accuracy (±1 kcal/mol), three corrections to the electronic energy were added to the frozen core CCSD(T)/CBS binding energies: corrections for core-valence, scalar relativistic, and first order atomic spin-orbit effects. Vibrational zero point energies were computed at the CCSD(T) level of theory where possible. The calculated heats of formation are in good agreement with the available experimental values, except for FOOF because of the neglect of higher order correlation corrections. The F(+) affinity in the N(x)F(y) series increases from N(2) to N(2)F(4) by 63 kcal/mol, while that in the O(2)F(y) series decreases by 18 kcal/mol from O(2) to O(2)F(2). Neither N(2) nor N(2)F(4) is predicted to bind F(-), and N(2)F(2) is a very weak Lewis acid with an F(-) affinity of about 10 kcal/mol for either the cis or trans isomer. The low F(-) affinities of the nitrogen fluorides explain why, in spite of the fact that many stable nitrogen fluoride cations are known, no nitrogen fluoride anions have been isolated so far. For example, the F(-) affinity of NF is predicted to be only 12.5 kcal/mol which explains the numerous experimental failures to prepare NF(2)(-) salts from the well-known strong acid HNF(2). The F(-) affinity of O(2) is predicted to have a small positive value and increases for O(2)F(2) by 23 kcal/mol, indicating that the O(2)F(3)(-) anion might be marginally stable at subambient temperatures. The calculated adiabatic ionization potentials and electron affinities are in good agreement with experiment considering that many of the experimental values are for vertical processes. © 2011

[An examination of the determinants of social withdrawal and affinity for social withdrawal].

Science.gov (United States)

Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

2010-12-01

This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

Affinity chromatography: A versatile technique for antibody purification.

Science.gov (United States)

Arora, Sushrut; Saxena, Vikas; Ayyar, B Vijayalakshmi

2017-03-01

Antibodies continue to be extremely utilized entities in myriad applications including basic research, imaging, targeted delivery, chromatography, diagnostics, and therapeutics. At production stage, antibodies are generally present in complex matrices and most of their intended applications necessitate purification. Antibody purification has always been a major bottleneck in downstream processing of antibodies, due to the need of high quality products and associated high costs. Over the years, extensive research has focused on finding better purification methodologies to overcome this holdup. Among a plethora of different techniques, affinity chromatography is one of the most selective, rapid and easy method for antibody purification. This review aims to provide a detailed overview on affinity chromatography and the components involved in purification. An array of support matrices along with various classes of affinity ligands detailing their underlying working principles, together with the advantages and limitations of each system in purifying different types of antibodies, accompanying recent developments and important practical methodological considerations to optimize purification procedure are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Current advances in screening for bioactive components from medicinal plants by affinity ultrafiltration mass spectrometry.

Science.gov (United States)

Chen, Guilin; Huang, Bill X; Guo, Mingquan

2018-05-21

Medicinal plants have played an important role in maintaining human health for thousands of years. However, the interactions between the active components in medicinal plants and some certain biological targets during a disease are still unclear in most cases. To conduct the high-throughput screening for small active molecules that can interact with biological targets, which is of great theoretical significance and practical value. The ultrafiltration mass spectrometry (UF-LC/MS) is a powerful bio-analytical method by combining affinity ultrafiltration and liquid chromatography-mass spectrometry (LC/MS), which could rapidly screen and identify small active molecules that bind to biological targets of interest at the same time. Compared with other analytical methods, affinity UF-LC/MS has the characteristics of fast, sensitive and high throughput, and is especially suitable for the complicated extracts of medicinal plants. In this review, the basic principle, characteristics and some most recent challenges in UF-LC/MS have been demonstrated. Meanwhile, the progress and applications of affinity UF-LC/MS in the discovery of the active components from natural medicinal plants and the interactions between small molecules and biological target proteins are also briefly summarised. In addition, the future directions for UF-LC/MS are also prospected. Affinity UF-LC/MS is a powerful tool in studies on the interactions between small active molecules and biological protein targets, especially in the high-throughput screening of active components from the natural medicinal plants. Copyright © 2018 John Wiley & Sons, Ltd.

Synthesis, biodistribution and in vitro evaluation of brain permeable high affinity type 2 cannabinoid receptor agonists [11C]MA2 and [18F]MA3

Directory of Open Access Journals (Sweden)

Muneer Ahamed

2016-09-01

Full Text Available Abstract The type 2 cannabinoid receptor (CB2 is a member of the endocannabinoid system and is known for its important role in (neuroinflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([11C]MA2 and a fluorine-18 ([18F]MA3 labeled analogue of a highly potent N-arylamide oxadiazole CB2 agonist (EC50 = 0.015 nM. MA2 and MA3 behaved as potent CB2 agonist (EC50: 3 nM and 0.1 nM, respectively and their in vitro binding affinity for hCB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group was found to have higher binding affinity and EC50 values when compared to the originally reported trifluoromethyl analogue 12. [11C]MA2 and [18F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [11C]MA2 and [18F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted.

5-(sulfonyl)oxy-tryptamines and ethylamino side chain restricted derivatives. Structure-affinity relationships for h5-HT1B and h5-HT1D receptors

NARCIS (Netherlands)

Barf, T; Wikstrom, H; Pauwels, PJ; Palmier, C; Tardif, S; Lundmark, M; Sundell, S

A number of sulfonic acid ester derivatives of serotonin (5-hydroxytryptamine; 5-HT; 1) were prepared and their affinities are compared to that of the reference compound 5-[[(trifluoromethyl)sulfonyl]oxy]-tryptamine (8b). The structure-affinity relationship (SAFIR) is discussed in terms of in vitro

A Novel Open Tubular Capillary Electrochromatographic Method for Differentiating the DNA Interaction Affinity of Environmental Contaminants.

Directory of Open Access Journals (Sweden)

Lucia D'Ulivo

Full Text Available The interaction of chemicals with DNA may lead to genotoxicity, mutation or carcinogenicity. A simple open tubular capillary electrochromatographic method is proposed to rapidly assess the interaction affinity of three environmental contaminants (1,4-phenylenediamine, pyridine and 2,4-diaminotoluene to DNA by measuring their retention in the capillaries coated with DNA probes. DNA oligonucleotide probes were immobilized on the inner wall of a fused silica capillary that was first derivatized with 3-(aminopropyl-triethoxysilane (APTES. The difference in retention times and factors was considered as the difference in interaction affinity of the contaminants to the DNA probes. The interaction of the contaminants with both double-stranded (dsDNA and single-stranded DNA (ssDNA coatings was compared. Retention factors of 1,4-phenylenediamine, pyridine and 2,4-diaminotoluene in the capillary coated with ssDNA probe were 0.29, 0.42, and 0.44, respectively. A similar trend was observed in the capillary coated with dsDNA, indicating that 2,4-diaminotoluene has the highest affinity among the three contaminants. The relative standard deviation (RSD for the retention factors was in the range of 0.05-0.69% (n = 3. The results demonstrated that the developed technique could be applied for preliminary screening purpose to provide DNA interaction affinity information of various environmental contaminants.

CT-3DRA registration for radiosurgery treatments: a comparison among rigid, affine and non rigid approaches

International Nuclear Information System (INIS)

Stancanello, J.; Loeckx, D.; Francescon, P.; Calvedon, C.; Avanzo, M.; Cora, S.; Scalchi, P.; Cerveri, P.; Ferrigno, G.

2004-01-01

This work aims at comparing rigid, affine and Local Non Rigid (LNR) CT-3D Rotational Angiography (CT-3DRA) registrations based on mutual information. 10 cranial and 1 spinal cases have been registered by rigid and affine transformations; while LNR has been applied to the cases where residual deformation must be corrected. An example of CT-3DRA registration without regularization term and an example of LNR using the similarity criterion and the regularization term as well as 3D superposition of the 3DRA before and after the registration without the regularization term are presented. All the registrations performed by rigid transformation converged to an acceptable solution. The results about the robustness test in axial direction are reported. Conclusions: For cranial cases, affine transformation endowed with threshold-segmentation pre-processing can be considered the most favourable solution for almost all registrations; for some cases, LNR provides more accurate results. For the spinal case rigid transformation is the most suitable when immobilizing patient during examinations; in this case the increase of accuracy by using LNR registrations seems to be not significant

Structure-based engineering to restore high affinity binding of an isoform-selective anti-TGFβ1 antibody

Science.gov (United States)

Honey, Denise M.; Best, Annie; Qiu, Huawei

2018-01-01

ABSTRACT Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering. Therefore, we designed insertion mutants in the elbow region and screened for binding and potency. Our results indicated that increasing the elbow region linker length in each chain successfully restored the isoform-specific and high affinity binding of CAT192 to TGFβ1. The crystal structure of the high binding affinity mutant displays large conformational rearrangements of the variable domains compared to the wild-type antigen-binding fragment (Fab) and the low binding affinity mutants. Insertion of two glycines in both the heavy and light chain elbow regions provided sufficient flexibility for the variable domains to extend further apart than the wild-type Fab, and allow the CDR3s to make additional interactions not seen in the wild-type Fab structure. These interactions coupled with the dramatic conformational changes provide a possible explanation of how the scFv and elbow-engineered Fabs bind TGFβ1 with high affinity. This study demonstrates the benefits of re-examining both structure and function when converting scFv to IgG molecules, and highlights the potential of structure-based engineering to produce fully functional antibodies. PMID:29333938

Affinity partitioning of human antibodies in aqueous two-phase systems.

Science.gov (United States)

Rosa, P A J; Azevedo, A M; Ferreira, I F; de Vries, J; Korporaal, R; Verhoef, H J; Visser, T J; Aires-Barros, M R

2007-08-24

The partitioning of human immunoglobulin (IgG) in a polymer-polymer and polymer-salt aqueous two-phase system (ATPS) in the presence of several functionalised polyethylene glycols (PEGs) was studied. As a first approach, the partition studies were performed with pure IgG using systems in which the target protein remained in the bottom phase when the non-functionalised systems were tested. The effect of increasing functionalised PEG concentration and the type of ligand were studied. Afterwards, selectivity studies were performed with the most successful ligands first by using systems containing pure proteins and an artificial mixture of proteins and, subsequently, with systems containing a Chinese hamster ovary (CHO) cells supernatant. The PEG/phosphate ATPS was not suitable for the affinity partitioning of IgG. In the PEG/dextran ATPS, the diglutaric acid functionalised PEGs (PEG-COOH) displayed great affinity to IgG, and all IgG could be recovered in the top phase when 20% (w/w) of PEG 150-COOH and 40% (w/w) PEG 3350-COOH were used. The selectivity of these functionalised PEGs was evaluated using an artificial mixture of proteins, and PEG 3350-COOH did not show affinity to IgG in the presence of typical serum proteins such as human serum albumin and myoglobin, while in systems with PEG 150-COOH, IgG could be recovered with a yield of 91%. The best purification of IgG from the CHO cells supernatant was then achieved in a PEG/dextran ATPS in the presence of PEG 150-COOH with a recovery yield of 93%, a purification factor of 1.9 and a selectivity to IgG of 11. When this functionalised PEG was added to the ATPS, a 60-fold increase in selectivity was observed when compared to the non-functionalised systems.

DFT study on the effect of exocyclic substituents on the proton affinity of 1-methylimidazole

International Nuclear Information System (INIS)

Liu, Haining; Bara, Jason E.; Turner, C. Heath

2013-01-01

Highlights: • DFT calculations are used to predict the proton affinity of 1-methylimidazoles. • The electron-withdrawing groups dominate the predicted proton affinity. • The effects of multiple substituents on the proton affinity can be accurately predicted. • Large compound libraries can be screened for imidazoles with tailored reactivity. - Abstract: A deeper understanding of the acid/base properties of imidazole derivatives will aid the development of solvents, polymer membranes and other materials that can be used for CO 2 capture and acid gas removal. In this study, we employ density functional theory calculations to investigate the effect of various electron-donating and electron-withdrawing groups on the proton affinity of 1-methylimidazole. We find that electron-donating groups are able to increase the proton affinity relative to 1-methylimidazole, i.e., making the molecule more basic. In contrast, electron-withdrawing groups cause a decrease of the proton affinity. When multiple substituents are present, their effects on the proton affinity were found to be additive. This finding offers a quick approach for predicting and targeting the proton affinities of this series of molecules, and we show the strong correlation between the calculated proton affinities and experimental pK a values

Density-conserving affine continuous cellular automata solving the relaxed density classification problem

International Nuclear Information System (INIS)

Wolnik, Barbara; Dembowski, Marcin; Bołt, Witold; Baetens, Jan M; De Baets, Bernard

2017-01-01

The focus of this paper is on the density classification problem in the context of affine continuous cellular automata. Although such cellular automata cannot solve this problem in the classical sense, most density-conserving affine continuous cellular automata with a unit neighborhood radius are valid solutions of a slightly relaxed version of this problem. This result follows from a detailed study of the dynamics of the density-conserving affine continuous cellular automata that we introduce. (paper)

HIGHER SERUM CAFFEINE IN SMOKERS WITH SCHIZOPHRENIA COMPARED TO SMOKING CONTROLS

OpenAIRE

Gandhi, Kunal K; Williams, Jill M; Menza, Matthew; Galazyn, Magdalena; Benowitz, Neal L.

2010-01-01

Previous studies of high dietary caffeine intake in individuals with schizophrenia have not demonstrated biological evidence of higher intake or controlled smoking behavior. This study aimed to examine differences in serum caffeine levels in 104 smokers with schizophrenia/schizoaffective disorder (SCZ/SA) and compare them to 63 smokers without any mental illness (CON). Since we were interested in measuring caffeine levels, we excluded all non caffeine users from the study. Blood draws were st...

Electrochemical affinity biosensors for detection of mycotoxins: A review.

Science.gov (United States)

Vidal, Juan C; Bonel, Laura; Ezquerra, Alba; Hernández, Susana; Bertolín, Juan R; Cubel, Carlota; Castillo, Juan R

2013-11-15

This review discusses the current state of electrochemical biosensors in the determination of mycotoxins in foods. Mycotoxins are highly toxic secondary metabolites produced by molds. The acute toxicity of these results in serious human and animal health problems, although it has been only since early 1960s when the first studied aflatoxins were found to be carcinogenic. Mycotoxins affect a broad range of agricultural products, most important cereals and cereal-based foods. A majority of countries, mentioning especially the European Union, have established preventive programs to control contamination and strict laws of the permitted levels in foods. Official methods of analysis of mycotoxins normally requires sophisticated instrumentation, e.g. liquid chromatography with fluorescence or mass detectors, combined with extraction procedures for sample preparation. For about sixteen years, the use of simpler and faster analytical procedures based on affinity biosensors has emerged in scientific literature as a very promising alternative, particularly electrochemical (i.e., amperometric, impedance, potentiometric or conductimetric) affinity biosensors due to their simplicity and sensitivity. Typically, electrochemical biosensors for mycotoxins use specific antibodies or aptamers as affinity ligands, although recombinant antibodies, artificial receptors and molecular imprinted polymers show potential utility. This article deals with recent advances in electrochemical affinity biosensors for mycotoxins and covers complete literature from the first reports about sixteen years ago. Copyright © 2013 Elsevier B.V. All rights reserved.

A Lyapunov method for stability analysis of piecewise-affine systems over non-invariant domains

Science.gov (United States)

Rubagotti, Matteo; Zaccarian, Luca; Bemporad, Alberto

2016-05-01

This paper analyses stability of discrete-time piecewise-affine systems, defined on possibly non-invariant domains, taking into account the possible presence of multiple dynamics in each of the polytopic regions of the system. An algorithm based on linear programming is proposed, in order to prove exponential stability of the origin and to find a positively invariant estimate of its region of attraction. The results are based on the definition of a piecewise-affine Lyapunov function, which is in general discontinuous on the boundaries of the regions. The proposed method is proven to lead to feasible solutions in a broader range of cases as compared to a previously proposed approach. Two numerical examples are shown, among which a case where the proposed method is applied to a closed-loop system, to which model predictive control was applied without a-priori guarantee of stability.

Na+,K+-ATPase Na+ affinity in rat skeletal muscle fiber types

DEFF Research Database (Denmark)

Kristensen, Michael; Juel, Carsten

2010-01-01

Previous studies in expression systems have found different ion activation of the Na(+)/K(+)-ATPase isozymes, which suggest that different muscles have different ion affinities. The rate of ATP hydrolysis was used to quantify Na(+),K(+)-ATPase activity, and the Na(+) affinity of Na(+),K(+)-ATPase...

Paper-based immune-affinity arrays for detection of multiple mycotoxins in cereals.

Science.gov (United States)

Li, Li; Chen, Hongpu; Lv, Xiaolan; Wang, Min; Jiang, Xizhi; Jiang, Yifei; Wang, Heye; Zhao, Yongfu; Xia, Liru

2018-03-01

Mycotoxins produced by different species of fungi may coexist in cereals and feedstuffs, and could be highly toxic for humans and animals. For quantification of multiple mycotoxins in cereals, we developed a paper-based mycotoxin immune-affinity array. First, paper-based microzone arrays were fabricated by photolithography. Then, monoclonal mycotoxin antibodies were added in a copolymerization reaction with a cross-linker to form an immune-affinity monolith on the paper-based microzone array. With use of a competitive immune-response format, paper-based mycotoxin immune-affinity arrays were successfully applied to detect mycotoxins in samples. The detection limits for deoxynivalenol, zearalenone, T-2 toxin, and HT-2 toxin were 62.7, 10.8, 0.36, and 0.23 μg·kg -1 , respectively, which meet relevant requirements for these compounds in food. The recovery rates were 81-86% for deoxynivalenol, 89-117% for zearalenone, 79-86% for T-2 toxin, and 78-83% for HT-2 toxin, and showed the paper-based immune-affinity arrays had good reproducibility. In summary, the paper-based mycotoxin immune-affinity array provides a sensitive, rapid, accurate, stable, and convenient platform for detection of multiple mycotoxins in agro-foods. Graphical abstract Paper-based immune-affinity monolithic array. DON deoxynivalenol, HT-2 HT-2 toxin, T-2 T-2 toxin, PEGDA polyethylene glycol diacrylate, ZEN zearalenone.

Fragment-based quantum mechanical calculation of protein-protein binding affinities.

Science.gov (United States)

Wang, Yaqian; Liu, Jinfeng; Li, Jinjin; He, Xiao

2018-04-29

The electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method has been successfully utilized for efficient linear-scaling quantum mechanical (QM) calculation of protein energies. In this work, we applied the EE-GMFCC method for calculation of binding affinity of Endonuclease colicin-immunity protein complex. The binding free energy changes between the wild-type and mutants of the complex calculated by EE-GMFCC are in good agreement with experimental results. The correlation coefficient (R) between the predicted binding energy changes and experimental values is 0.906 at the B3LYP/6-31G*-D level, based on the snapshot whose binding affinity is closest to the average result from the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculation. The inclusion of the QM effects is important for accurate prediction of protein-protein binding affinities. Moreover, the self-consistent calculation of PB solvation energy is required for accurate calculations of protein-protein binding free energies. This study demonstrates that the EE-GMFCC method is capable of providing reliable prediction of relative binding affinities for protein-protein complexes. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Efficient fabrication of high-capacity immobilized metal ion affinity chromatographic media: The role of the dextran-grafting process and its manipulation.

Science.gov (United States)

Zhao, Lan; Zhang, Jingfei; Huang, Yongdong; Li, Qiang; Zhang, Rongyue; Zhu, Kai; Suo, Jia; Su, Zhiguo; Zhang, Zhigang; Ma, Guanghui

2016-03-01

Novel high-capacity Ni(2+) immobilized metal ion affinity chromatographic media were prepared through the dextran-grafting process. Dextran was grafted to an allyl-activated agarose-based matrix followed by functionalization for the immobilized metal ion affinity chromatographic media. With elaborate regulation of the allylation degree, dextran was completely or partly grafted to agarose microspheres, namely, completely dextran-grafted agarose microspheres and partly dextran-grafted ones, respectively. Confocal laser scanning microscope results demonstrated that a good adjustment of dextran-grafting degree was achieved, and dextran was distributed uniformly in whole completely dextran-grafted microspheres, while just distributed around the outside of the partly dextran-grafted ones. Flow hydrodynamic properties were improved greatly after the dextran-grafting process, and the flow velocity increased by about 30% compared with that of a commercial chromatographic medium (Ni Sepharose FF). A significant improvement of protein binding performance was also achieved by the dextran-grafting process, and partly dextran-grafted Ni(2+) chelating medium had a maximum binding capacity for His-tagged lactate dehydrogenase about 2.5 times higher than that of Ni Sepharose FF. The results indicated that this novel chromatographic medium is promising for applications in high-efficiency and large-scale protein purification. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces.

Science.gov (United States)

Sankaran, Shrikrishnan; Cavatorta, Emanuela; Huskens, Jurriaan; Jonkheijm, Pascal

2017-09-05

Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV 2+ ). The binding affinity of the knottins with CB[8] and MV 2+ surfaces was evaluated using surface plasmon resonance spectroscopy. Specific binding occurred, and the affinity increased with the valency of tryptophans on the knottin. Additionally, increased multilayer formation was observed, attributed to homoternary complex formation between tryptophan residues of different knottins and CB[8]. Thus, we were able to control the surface coverage of the knottins by valency and concentration. Cell experiments with mouse myoblast (C2C12) cells on the self-assembled knottin surfaces showed specific integrin recognition by the RGD-displaying knottins. Moreover, cells were observed to elongate more on the supramolecular knottin surfaces with a higher valency, and in addition, more pronounced focal adhesion formation was observed on the higher-valency knottin surfaces. We attribute this effect to the enhanced coverage and the enhanced affinity of the knottins in their interaction with the CB[8] surface. Collectively, these results are promising for the development of biomaterials including knottins via CB[8] ternary complexes for tunable interactions with cells.

Accurate and sensitive quantification of protein-DNA binding affinity.

Science.gov (United States)

Rastogi, Chaitanya; Rube, H Tomas; Kribelbauer, Judith F; Crocker, Justin; Loker, Ryan E; Martini, Gabriella D; Laptenko, Oleg; Freed-Pastor, William A; Prives, Carol; Stern, David L; Mann, Richard S; Bussemaker, Harmen J

2018-04-17

Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes. Copyright © 2018 the Author(s). Published by PNAS.

Electron affinities, molecular structures, and thermochemistry of the fluorine, chlorine and bromine substituted methyl radicals

Science.gov (United States)

Li, Qian-Shu; Zhao, Jun-Fang; Xie, Yaoming; Schaefer, Henry F., III

Four independent density functional theory (DFT) methods have been employed to study the structures and electron affinities of the methyl and F-, Cl- and Br-substituted methyl radicals and their anions. The methods used have been carefully calibrated against a comprehensive tabulation of experimental electron affinities (Chemical Reviews, 2002, 102, 231). The first dissociation energies together with the vibrational frequencies of these species are also reported. The basis sets used in this work are of double- ζ plus polarization quality with additional s- and p-type diffuse functions, labelled as DZP++. Previously observed trends in the prediction of bond lengths by the DFT methods are also demonstrated for the F-, Cl- and Br-substituted methyl radicals and their anions. Generally, the Hartree-Fock/DFT hybrid methods predict shorter and more reliable bond lengths than the pure DFT methods. Neutral-anion energy differences reported in this work are the adiabatic electron affinity (EAad), the vertical electron affinity (EAvert), and the vertical detachment energy (VDE). Compared with the available experimental electron affinities, the BHLYP method predicts much lower values, while the other methods predict values (EAad, EAvert, VDE) close to each other and almost within the experimental range. For those systems without reliable experimental measurements, our best adiabatic EAs predicted by BLYP are 0.78 (CHF2), 1.23 (CHFCl), 1.44 (CHFBr), 1.61 (CHClBr), 2.24 (CF2Cl), 2.42 (CF2Br), 2.56 (CFBr2), 2.36 (CCl2Br), 2.46 (CClBr2), and 2.44 eV (CFClBr). The most striking feature of these predictions is that they display an inverse relationship between halogen electronegativity and EA. The DZP++ B3LYP method determines the vibrational frequencies in best agreement with available experimental results for this series, with an average relative error of ~2%. The value of using a variety of DFT methods is observed in that BHLYP does best for geometries, BLYP for electron

Higher-genus su(N) fusion multiplicities as polytope volumes

International Nuclear Information System (INIS)

Flynn, G; Rasmussen, J; Tahic, M; Walton, M A

2002-01-01

We show how higher-genus su(N) fusion multiplicities may be computed as the discretized volumes of certain polytopes. The method is illustrated by explicit analyses of some su(3) and su(4) fusions, but applies to all higher-point and higher-genus su(N) fusions. It is based on an extension of the realm of Berenstein-Zelevinsky triangles by including so-called gluing and loop-gluing diagrams. The identification of the loop-gluing diagrams is our main new result, since they enable us to characterize higher-genus fusions in terms of polytopes. Also, the genus-2 0-point su(3) fusion multiplicity is found to be a simple binomial coefficient in the affine level

Constraints on the affinity term for modeling long-term glass dissolution rates

International Nuclear Information System (INIS)

Bourcier, W.L.; Carroll, S.A.; Phillips, B.L.

1993-11-01

Predictions of long-term glass dissolution rates are highly dependent on the form of the affinity term in the rate expression. Analysis of the quantitative effect of saturation state on glass dissolution rate for CSG glass (a simple analog of SRL-165 glass), shows that a simple (1-Q/K) affinity term does not match experimental results. Our data at 100 degree C show that the data is better fit by an affinity term having the form (1 - (Q/K) 1 /σ) where σ = 10

Identification of an adeno-associated virus binding epitope for AVB sepharose affinity resin

Directory of Open Access Journals (Sweden)

Qiang Wang

Full Text Available Recent successes of adeno-associated virus (AAV–based gene therapy have created a demand for large-scale AAV vector manufacturing and purification techniques for use in clinical trials and beyond. During the development of purification protocols for rh.10, hu.37, AAV8, rh.64R1, AAV3B, and AAV9 vectors, based on a widely used affinity resin, AVB sepharose (GE, we found that, under the same conditions, different serotypes have different affinities to the resin, with AAV3B binding the best and AAV9 the poorest. Further analysis revealed a surface-exposed residue (amino acid number 665 in AAV8 VP1 numbering differs between the high-affinity AAV serotypes (serine in AAV3B, rh.10, and hu.37 and the low-affinity ones (asparagine in AAV8, rh.64R1, and AAV9. The residue locates within a surface-exposed, variable epitope flanked by highly conserved residues. The substitution of the epitope in AAV8, rh.64R1, and AAV9 with the corresponding epitope of AAV3B (SPAKFA resulted in greatly increased affinity to AVB sepharose with no reduction in the vectors’ in vitro potency. The presence of the newly identified AVB-binding epitope will be useful for affinity resin selection for the purification of novel AAV serotypes. It also suggests the possibility of vector engineering to yield a universal affinity chromatography purification method for multiple AAV serotypes.

Identification of Thioredoxin Target Disulfides Using Isotope-Coded Affinity Tags

DEFF Research Database (Denmark)

Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

2014-01-01

Thioredoxins (Trx) are small redox proteins that reduce disulfide bonds in various target proteins and maintain cellular thiol redox control. Here, a thiol-specific labeling and affinity enrichment approach for identification and relative quantification of Trx target disulfides in complex protein...... reduction is determined by LC-MS/MS-based quantification of tryptic peptides labeled with "light" (12C) and "heavy" (13C) ICAT reagents. The methodology can be adapted to monitor the effect of different reductants or oxidants on the redox status of thiol/disulfide proteomes in biological systems....... extracts is described. The procedure utilizes the isotope-coded affinity tag (ICAT) reagents containing a thiol reactive iodoacetamide group and a biotin affinity tag to target peptides containing reduced cysteine residues. The identification of substrates for Trx and the extent of target disulfide...

Affinity purification of recombinant human plasminogen activator ...

African Journals Online (AJOL)

Affinity purification of recombinant human plasminogen activator from ... Screening antibody was performed using rhPA milk in an ELISA-elution assay. ... useful for purifying other tPA mutants or other novel recombinant milkderived proteins.

Microfluidics in the selection of affinity reagents for the detection of cancer: paving a way towards future diagnostics.

Science.gov (United States)

Hung, Lien-Yu; Wang, Chih-Hung; Fu, Chien-Yu; Gopinathan, Priya; Lee, Gwo-Bin

2016-08-07

Microfluidic technologies have miniaturized a variety of biomedical applications, and these chip-based systems have several significant advantages over their large-scale counterparts. Recently, this technology has been used for automating labor-intensive and time-consuming screening processes, whereby affinity reagents, including aptamers, peptides, antibodies, polysaccharides, glycoproteins, and a variety of small molecules, are used to probe for molecular biomarkers. When compared to conventional methods, the microfluidic approaches are faster, more compact, require considerably smaller quantities of samples and reagents, and can be automated. Furthermore, they allow for more precise control of reaction conditions (e.g., pH, temperature, and shearing forces) such that more efficient screening can be performed. A variety of affinity reagents for targeting cancer cells or cancer biomarkers are now available and will likely replace conventional antibodies. In this review article, the selection of affinity reagents for cancer cells or cancer biomarkers on microfluidic platforms is reviewed with the aim of highlighting the utility of such approaches in cancer diagnostics.

Evaluation Codes from an Affine Veriety Code Perspective

DEFF Research Database (Denmark)

Geil, Hans Olav

2008-01-01

Evaluation codes (also called order domain codes) are traditionally introduced as generalized one-point geometric Goppa codes. In the present paper we will give a new point of view on evaluation codes by introducing them instead as particular nice examples of affine variety codes. Our study...... includes a reformulation of the usual methods to estimate the minimum distances of evaluation codes into the setting of affine variety codes. Finally we describe the connection to the theory of one-pointgeometric Goppa codes. Contents 4.1 Introduction...... . . . . . . . . . . . . . . . . . . . . . . . 171 4.9 Codes form order domains . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 4.10 One-point geometric Goppa codes . . . . . . . . . . . . . . . . . . . . . . . . 176 4.11 Bibliographical Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 References...

Higher prevalence of anemia among pregnant immigrant women compared to pregnant ethnic Danish women

DEFF Research Database (Denmark)

Nybo, Mads; Friis-Hansen, Lennart; Felding, Peter

2007-01-01

The aim of the study was to investigate whether the well-known high anemia prevalence in pregnant women from the eastern Mediterranean and Asian regions decreased when the women immigrated to a low-frequency region (Denmark). During 70 months, 1,741 pregnant immigrant women referred from primary...... status parameters were examined in the two groups. The prevalence of anemia was higher in the immigrant group (20.0%) compared to the Danish women (4.9%) (P ... indicated iron deficiency. Conclusively, the pregnant immigrant women had significantly higher prevalence of anemia compared to pregnant women of Danish origin. It indicates the need for an alternative routine screening procedure for this population group, which should also include nutritional counselling....

Domain interplay in the urokinase receptor. Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains

DEFF Research Database (Denmark)

Behrendt, N; Ronne, E; Dano, K

1996-01-01

by chemical cross-linking, but quantitative binding/competition studies showed that the apparent ligand affinity was 100- to 1000-fold lower than that of the intact suPAR. This loss of affinity was comparable with the loss found after cleavage between the first domain (D1) and D(2 + 3), using chymotrypsin...

The Purification of a Blood Group A Glycoprotein: An Affinity Chromatography Experiment.

Science.gov (United States)

Estelrich, J.; Pouplana, R.

1988-01-01

Describes a purification process through affinity chromatography necessary to obtain specific blood group glycoproteins from erythrocytic membranes. Discusses the preparation of erythrocytic membranes, extraction of glycoprotein from membranes, affinity chromatography purification, determination of glycoproteins, and results. (CW)

GABAB Receptor Constituents Revealed by Tandem Affinity Purification from Transgenic Mice

DEFF Research Database (Denmark)

Bartoi, Tudor; Rigbolt, Kristoffer T G; Du, Dan

2010-01-01

lines that allow a straightforward biochemical isolation of GABA(B) receptors. The transgenic mice express GABA(B1) isoforms that contain sequences for a two-step affinity purification, in addition to their endogenous subunit repertoire. Comparative analyses of purified samples from the transgenic mice...... and wild-type control animals revealed two novel components of the GABA(B1) complex. One of the identified proteins, potassium channel tetramerization domain-containing protein 12, associates with heterodimeric GABA(B) receptors via the GABA(B2) subunit. In transfected hippocampal neurons, potassium...

Quantum deformation of the affine transformation algebra

International Nuclear Information System (INIS)

Aizawa, N.; Sato, Haru-Tada

1994-01-01

We discuss a quantum deformation of the affine transformation algebra in one-dimensional space. It is shown that the quantum algebra has a non-cocommutative Hopf algebra structure, simple realizations and quantum tensor operators. (orig.)

Cyclization strategies of meditopes: affinity and diffraction studies of meditope–Fab complexes

International Nuclear Information System (INIS)

Bzymek, Krzysztof P.; Ma, Yuelong; Avery, Kendra A.; Horne, David A.; Williams, John C.

2016-01-01

An overview of cyclization strategies of a Fab-binding peptide to maximize affinity. Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic ‘pocket’ and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope–Fab complex

Cyclization strategies of meditopes: affinity and diffraction studies of meditope–Fab complexes

Energy Technology Data Exchange (ETDEWEB)

Bzymek, Krzysztof P.; Ma, Yuelong; Avery, Kendra A.; Horne, David A.; Williams, John C., E-mail: jcwilliams@coh.org [Beckman Research Institute of City of Hope, 1710 Flower Street, Duarte, CA 91010 (United States)

2016-05-23

An overview of cyclization strategies of a Fab-binding peptide to maximize affinity. Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic ‘pocket’ and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope–Fab complex.

IA-2 autoantibody affinity in children at risk for type 1 diabetes.

Science.gov (United States)

Krause, Stephanie; Chmiel, Ruth; Bonifacio, Ezio; Scholz, Marlon; Powell, Michael; Furmaniak, Jadwiga; Rees Smith, Bernard; Ziegler, Anette-G; Achenbach, Peter

2012-12-01

Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 10(7) to 10(11)L/mol and was high (>1.0×10(9)L/mol) in 41 (82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2β. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development. Copyright © 2012 Elsevier Inc. All rights reserved.

Dual Affinity Heparin-Based Hydrogels Achieve Pro-Regenerative Immunomodulation and Microvascular Remodeling.

Science.gov (United States)

Ogle, Molly E; Krieger, Jack R; Tellier, Liane E; McFaline-Figueroa, Jennifer; Temenoff, Johnna S; Botchwey, Edward A

2018-04-09

The immune response to biomaterial implants critically regulates functional outcomes such as vascularization, transplant integration/survival, and fibrosis. To create "immunologically smart" materials, the host-material response may be engineered to optimize the recruitment of pro-regenerative leukocyte subsets which mature into corresponding wound-healing macrophages. We have recently identified a unique feature of pro-regenerative Ly6C low monocytes that is a higher expression of both the bioactive lipid receptor sphingosine-1-phosphate receptor 3 (S1PR3) and the stromal derived factor-1α (SDF-1α) receptor CXCR4. Therefore, we designed a bifunctional hydrogel to harnesses a mechanistic synergy between these signaling axes to enhance the recruitment of endogenous pro-regenerative monocytes. To overcome the challenge of codelivering two physiochemically distinct molecules-a large hydrophilic protein and hydrophobic small molecule-we engineered a dual affinity hydrogel that exploits the growth factor affinity of a heparin derivative (Hep -N ) and lipid chaperone activity of albumin. The sphingosine analog FTY720 and SDF-1α are successfully loaded and coreleased from the Hep -N -functionalized PEG-DA hydrogels while maintaining bioactivity. Placement of these hydrogels into a murine partial thickness skin wound demonstrates that corelease of FTY720 and SDF-1α yields superior recruitment of myeloid cells to the implant interface compared to either factor alone. Although in vivo delivery of FTY720 or SDF-1α individually promotes the enhanced recruitment of Ly-6C low anti-inflammatory monocytes, codelivery enhances the early accumulation and persistence of the differentiated wound healing CD206 + macrophages in the tissue surrounding the gel. Co-delivery similarly promoted the synergistic expansion of vasculature adjacent to the implant, a key step in tissue healing. Taken together, these findings suggest that the combination of chemotactic molecules may provide

Low uptake affinity cultivars with biochar to tackle Cd-tainted rice — A field study over four rice seasons in Hunan, China

International Nuclear Information System (INIS)

Chen, De; Guo, Hu; Li, Ruiyue; Li, Lianqing; Pan, Genxing; Chang, Andrew; Joseph, Stephen

2016-01-01

Biochar is becoming an environmentally friendly material for remediation of heavy metal contaminated soils and improving food safety. A field trial over four rice seasons was conducted to investigate the use of biochar and low Cd accumulating cultivars on Cd uptake in a heavy metal contaminated soil. Wheat straw derived biochar was applied at 0, 20 and 40 t ha"−"1. Two rice cultivars with differing Cd accumulation abilities were selected in each season. The results showed that both biochar and low Cd affinity cultivars significantly reduced rice grain Cd accumulation. Biochar had no significant effect the first season but thereafter consistently reduced rice grain Cd by a maximum of 61, 86 and 57% over the next three seasons. Zn accumulation in the rice grains was not decreased by biochar application, although available soil Zn was sharply reduced (35–91%). Indica conventional rice cultivars had much lower Cd, but higher Zn and lower Cd/Zn ratios in the grain than indica hybrid cultivars. Biochar was more effective for mitigating grain Cd accumulation in low Cd affinity cultivars than in high affinity cultivars. Soil pH was sustainably increased (up to nearly 1 unit) while available Cd significantly decreased by a maximum of 85% after biochar addition. The translocation of Cd from rice roots to shoots was reduced from 20 to 80% by biochar. Low uptake affinity cultivars combined with biochar reduced late rice grain Cd concentration and Cd/Zn ratios by 69–80% and 72–80%, respectively. It indicated that the management of combining biochar and low Cd affinity cultivars should be an efficient way to remediate Cd contaminated rice paddies and reduce health risk associated with consuming rice from these soils. - Highlights: • Biochar sustainably reduced soil Cd availability and Cd translocation in rice plant. • Indica conventional cultivars had lower Cd but higher Zn in grains than hybrid ones. • Biochar significantly reduced grain Cd and Cd/Zn ratio, though

On dynamic equations for interaction of the affinor field with affine connection

International Nuclear Information System (INIS)

Pestov, A.B.

1987-01-01

The Lagrangian of interaction of an affinor field with an affine connection is constructed and the equations of motion and conservation laws are derived. It is shown that there exists a symmetric conserved tensor of the affine-connection energy-momentum

Affinity for Quantitative Tools: Undergraduate Marketing Students Moving beyond Quantitative Anxiety

Science.gov (United States)

Tarasi, Crina O.; Wilson, J. Holton; Puri, Cheenu; Divine, Richard L.

2013-01-01

Marketing students are known as less likely to have an affinity for the quantitative aspects of the marketing discipline. In this article, we study the reasons why this might be true and develop a parsimonious 20-item scale for measuring quantitative affinity in undergraduate marketing students. The scale was administered to a sample of business…

Relationship of nonreturn rates of dairy bulls to binding affinity of heparin to sperm

International Nuclear Information System (INIS)

Marks, J.L.; Ax, R.L.

1985-01-01

The binding of the glycosaminoglycan [ 3 H] heparin to bull spermatozoa was compared with nonreturn rates of dairy bulls. Semen samples from five bulls above and five below an average 71% nonreturn rate were used. Samples consisted of first and second ejaculates on a single day collected 1 d/wk for up to 5 consecutive wk. Saturation binding assays using [ 3 H] heparin were performed to quantitate the binding characteristics of each sample. Scatchard plot analyses indicated a significant difference in the binding affinity for [ 3 H] heparin between bulls of high and low fertility. Dissociation constants were 69.0 and 119.3 pmol for bulls of high and low fertility, respectively. In contrast, the number of binding sites for [ 3 H] heparin did not differ significantly among bulls. Differences in binding affinity of [ 3 H] heparin to bull sperm might be used to predict relative fertility of dairy bulls

Politics and Culture in Croation Higher Education: A Comparative Perspective on Educational Reform.

Science.gov (United States)

Reichard, Max

1992-01-01

Offers a historical overview of a series of reforms of higher education in the former Yugoslavia republic, stressing the cultural importance of "obrazovanje" (formal education/training) and "odgoj" (moral education/personal development) in Croatia. Describes the development of "visa skola," comparable to U.S.…

Comparing Higher Education Practices and Cultural Competences in Kenya and the United States

Science.gov (United States)

Musamali, Kennedy; Martin, Barbara N.

2016-01-01

Examined within this paper are effective leadership practices across two cultures. Specifically, this study examined the relationship between cultural competency and effective leadership practices in higher education institutions. A quantitative design was used to investigate and compare effective practices of educational leaders in two distinct…

Solitons and the energy-momentum tensor for affine Toda theory

Science.gov (United States)

Olive, D. I.; Turok, N.; Underwood, J. W. R.

1993-07-01

Following Leznov and Saveliev, we present the general solution to Toda field theories of conformal, affine or conformal affine type, associated with a simple Lie algebra g. These depend on a free massless field and on a group element. By putting the former to zero, soliton solutions to the affine Toda theories with imaginary coupling constant result with the soliton data encoded in the group element. As this requires a reformulation of the affine Kac-Moody algebra closely related to that already used to formulate the physical properties of the particle excitations, including their scattering matrices, a unified treatment of particles and solitons emerges. The physical energy—momentum tensor for a general solution is broken into a total derivative plus a part dependent only on the derivatives of the free field. Despite the non-linearity of the field equations and their complex nature the energy and momentum of the N-soliton solution is shown to be real, equalling the sum of contributions from the individual solitons. There are rank-g species of soliton, with masses given by a generalisation of a formula due to Hollowood, being proportional to the components of the left Perron-Frobenius eigenvector of the Cartan matrix of g.

Solitons and the energy-momentum tensor for affine Toda theory

International Nuclear Information System (INIS)

Olive, D.I.; Turok, N.; Underwood, J.W.R.

1993-01-01

Following Leznov and Saveliev, we present the general solution to Toda field theories of conformal, affine or conformal affine type, associated with a simple Lie algebra g. These depend on a free massless field and on a group element. By putting the former to zero, soliton solutions to the affine Toda theories with imaginary coupling constant result with the soliton data encoded in the group element. As this requires a reformulation of the affine Kac-Moodyy algebra closely related to that already used to formulate the physical properties of the particle excitations, including their scattering matrices, a unified treatment of particles and solitons emerges. The physical energy-momentum tensor for a general solution is broken into a total derivative plus a part dependent only on the derivatives of the free field. Despite the non-linearity of the field equations and their complex nature the energy and momentum of the N-soliton solution is shown to be real, equalling the sum of contributions from the individual solitons. There are rank-g species of soliton, with masses given by a generalisation of a formula due to Hollowood, being proportional to the components of the left Perron-Frobenius eigenvector of the Cartan matrix of g. (orig.)

Affine invariants of convex polygons.

Science.gov (United States)

Flusser, Jan

2002-01-01

In this correspondence, we prove that the affine invariants, for image registration and object recognition, proposed recently by Yang and Cohen (see ibid., vol.8, no.7, p.934-46, July 1999) are algebraically dependent. We show how to select an independent and complete set of the invariants. The use of this new set leads to a significant reduction of the computing complexity without decreasing the discrimination power.

Specific capture of uranyl protein targets by metal affinity chromatography

International Nuclear Information System (INIS)

Basset, C.; Dedieu, A.; Guerin, P.; Quemeneur, E.; Meyer, D.; Vidaud, C.

2008-01-01

To improve general understanding of biochemical mechanisms in the field of uranium toxicology, the identification of protein targets needs to be intensified. Immobilized metal affinity chromatography (IMAC) has been widely developed as a powerful tool for capturing metal binding proteins from biological extracts. However uranyl cations (UO 2 2+ ) have particular physico-chemical characteristics which prevent them from being immobilized on classical metal chelating supports. We report here on the first development of an immobilized uranyl affinity chromatography method, based on the cation-exchange properties of amino-phosphonate groups for uranyl binding. The cation distribution coefficient and loading capacity on the support were determined. Then the stability of the uranyl-bonded phase under our chromatographic conditions was optimized to promote affinity mechanisms. The successful enrichment of uranyl binding proteins from human serum was then proven using proteomic and mass spectral analysis. (authors)

Use of Intrinsic Viscosity for evaluation of polymer-solvent affinity

DEFF Research Database (Denmark)

Marani, Debora; Hjelm, Johan; Wandel, Marie

2013-01-01

The objective of the current paper was to define a rheological method for the study of the solvent/binder affinity. The adopted strategy involves the study of the intrinsic viscosity [η] of polymer solutions. [η] was estimated via an extrapolation procedure using the Huggins and Kramer equations....... The intrinsic viscosity and the Mark-Houwink shape parameter were estimated for the three polymers and used as criteria for estimating the polymer/solvent affinity....

Scaffold hopping from (5-hydroxymethyl) isophthalates to multisubstituted pyrimidines diminishes binding affinity to the C1 domain of protein kinase C.

Science.gov (United States)

Provenzani, Riccardo; Tarvainen, Ilari; Brandoli, Giulia; Lempinen, Antti; Artes, Sanna; Turku, Ainoleena; Jäntti, Maria Helena; Talman, Virpi; Yli-Kauhaluoma, Jari; Tuominen, Raimo K; Boije Af Gennäs, Gustav

2018-01-01

Protein kinase C (PKC) isoforms play a pivotal role in the regulation of numerous cellular functions, making them extensively studied and highly attractive drug targets. Utilizing the crystal structure of the PKCδ C1B domain, we have developed hydrophobic isophthalic acid derivatives that modify PKC functions by binding to the C1 domain of the enzyme. In the present study, we aimed to improve the drug-like properties of the isophthalic acid derivatives by increasing their solubility and enhancing the binding affinity. Here we describe the design and synthesis of a series of multisubstituted pyrimidines as analogs of C1 domain-targeted isophthalates and characterize their binding affinities to the PKCα isoform. In contrast to our computational predictions, the scaffold hopping from phenyl to pyrimidine core diminished the binding affinity. Although the novel pyrimidines did not establish improved binding affinity for PKCα compared to our previous isophthalic acid derivatives, the present results provide useful structure-activity relationship data for further development of ligands targeted to the C1 domain of PKC.

Einstein’s gravity from a polynomial affine model

Science.gov (United States)

Castillo-Felisola, Oscar; Skirzewski, Aureliano

2018-03-01

We show that the effective field equations for a recently formulated polynomial affine model of gravity, in the sector of a torsion-free connection, accept general Einstein manifolds—with or without cosmological constant—as solutions. Moreover, the effective field equations are partially those obtained from a gravitational Yang–Mills theory known as Stephenson–Kilmister–Yang theory. Additionally, we find a generalization of a minimally coupled massless scalar field in General Relativity within a ‘minimally’ coupled scalar field in this affine model. Finally, we present a brief (perturbative) analysis of the propagators of the gravitational theory, and count the degrees of freedom. For completeness, we prove that a Birkhoff-like theorem is valid for the analyzed sector.

The governance of higher education regionalisation: comparative analysis of the Bologna Process and MERCOSUR-Educativo

NARCIS (Netherlands)

Verger, A.; Hermo, J.P.

2010-01-01

The article analyses two processes of higher education regionalisation, MERCOSUR‐Educativo in Latin America and the Bologna Process in Europe, from a comparative perspective. The comparative analysis is centered on the content and the governance of both processes and, specifically, on the reasons of

Analysis of Biological Interactions by Affinity Chromatography: Clinical and Pharmaceutical Applications.

Science.gov (United States)

Hage, David S

2017-06-01

The interactions between biochemical and chemical agents in the body are important in many clinical processes. Affinity chromatography and high-performance affinity chromatography (HPAC), in which a column contains an immobilized biologically related binding agent, are 2 methods that can be used to study these interactions. This review presents various approaches that can be used in affinity chromatography and HPAC to characterize the strength or rate of a biological interaction, the number and types of sites that are involved in this process, and the interactions between multiple solutes for the same binding agent. A number of applications for these methods are examined, with an emphasis on recent developments and high-performance affinity methods. These applications include the use of these techniques for fundamental studies of biological interactions, high-throughput screening of drugs, work with modified proteins, tools for personalized medicine, and studies of drug-drug competition for a common binding agent. The wide range of formats and detection methods that can be used with affinity chromatography and HPAC for examining biological interactions makes these tools attractive for various clinical and pharmaceutical applications. Future directions in the development of small-scale columns and the coupling of these methods with other techniques, such as mass spectrometry or other separation methods, should continue to increase the flexibility and ease with which these approaches can be used in work involving clinical or pharmaceutical samples. © 2016 American Association for Clinical Chemistry.

The affine quantum gravity programme

International Nuclear Information System (INIS)

Klauder, John R

2002-01-01

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

Sugawara construction for affine SL(N,1)

International Nuclear Information System (INIS)

Henningson, M.

1990-01-01

We investigate the sl(N,1) superalgebras, their affine extensions and their representations. This is used to perform a Sugawara construction of the Virasoro algebra. The allowed values of the conformal anomaly and the conformal dimension are computed. (orig.)

Internationalising Nordic higher education: comparing the imagined with actual worlds of international scholar-practitioners

Directory of Open Access Journals (Sweden)

Meeri Hellstén

2018-01-01

Full Text Available This comparative case study addresses a timely issue engaging researchers involved in the internationalisation of Nordic Higher Education, in the context of Sweden and Finland. The study examines a hypothetical imaginary in the transition between university international policy statements and their understandings from the position of a globalised episteme. The investigation forms a tag-project as part of a funded large international research project examining ethical internationalism in times of global crises, involving a partnership between more than twenty higher education institutions in excess of ten countries across five continents. The data was collected using a mixed-methods design, whilst being controlled across the matched data collection period in 2013-2014. Data consisted of policy texts, surveys and interviews. The current research inquiry reports on a within and across comparative analyses of certain policy texts and follow-up interviews with university management. The results yield logical support for a global higher education imaginary driving internationalisation in ways which reveal paradoxical associations between the imagined and the real worlds of international scholar-practitioners.

High-throughput fragment screening by affinity LC-MS.

Science.gov (United States)

Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Isaksson, Roland; Ohlson, Sten

2013-02-01

Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K (D)) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.

Effect of the Flexible Regions of the Oncoprotein Mouse Double Minute X on Inhibitor Binding Affinity.

Science.gov (United States)

Qin, Lingyun; Liu, Huili; Chen, Rong; Zhou, Jingjing; Cheng, Xiyao; Chen, Yao; Huang, Yongqi; Su, Zhengding

2017-11-07

The oncoprotein MdmX (mouse double minute X) is highly homologous to Mdm2 (mouse double minute 2) in terms of their amino acid sequences and three-dimensional conformations, but Mdm2 inhibitors exhibit very weak affinity for MdmX, providing an excellent model for exploring how protein conformation distinguishes and alters inhibitor binding. The intrinsic conformation flexibility of proteins plays pivotal roles in determining and predicting the binding properties and the design of inhibitors. Although the molecular dynamics simulation approach enables us to understand protein-ligand interactions, the mechanism underlying how a flexible binding pocket adapts an inhibitor has been less explored experimentally. In this work, we have investigated how the intrinsic flexible regions of the N-terminal domain of MdmX (N-MdmX) affect the affinity of the Mdm2 inhibitor nutlin-3a using protein engineering. Guided by heteronuclear nuclear Overhauser effect measurements, we identified the flexible regions that affect inhibitor binding affinity around the ligand-binding pocket on N-MdmX. A disulfide engineering mutant, N-MdmX C25-C110/C76-C88 , which incorporated two staples to rigidify the ligand-binding pocket, allowed an affinity for nutlin-3a higher than that of wild-type N-MdmX (K d ∼ 0.48 vs K d ∼ 20.3 μM). Therefore, this mutant provides not only an effective protein model for screening and designing of MdmX inhibitors but also a valuable clue for enhancing the intermolecular interactions of the pharmacophores of a ligand with pronounced flexible regions. In addition, our results revealed an allosteric ligand-binding mechanism of N-MdmX in which the ligand initially interacts with a compact core, followed by augmenting intermolecular interactions with intrinsic flexible regions. This strategy should also be applicable to many other protein targets to accelerate drug discovery.

Gaussian and Affine Approximation of Stochastic Diffusion Models for Interest and Mortality Rates

Directory of Open Access Journals (Sweden)

Marcus C. Christiansen

2013-10-01

Full Text Available In the actuarial literature, it has become common practice to model future capital returns and mortality rates stochastically in order to capture market risk and forecasting risk. Although interest rates often should and mortality rates always have to be non-negative, many authors use stochastic diffusion models with an affine drift term and additive noise. As a result, the diffusion process is Gaussian and, thus, analytically tractable, but negative values occur with positive probability. The argument is that the class of Gaussian diffusions would be a good approximation of the real future development. We challenge that reasoning and study the asymptotics of diffusion processes with affine drift and a general noise term with corresponding diffusion processes with an affine drift term and an affine noise term or additive noise. Our study helps to quantify the error that is made by approximating diffusive interest and mortality rate models with Gaussian diffusions and affine diffusions. In particular, we discuss forward interest and forward mortality rates and the error that approximations cause on the valuation of life insurance claims.

Analytical FcRn affinity chromatography for functional characterization of monoclonal antibodies

Science.gov (United States)

Schlothauer, Tilman; Rueger, Petra; Stracke, Jan Olaf; Hertenberger, Hubert; Fingas, Felix; Kling, Lothar; Emrich, Thomas; Drabner, Georg; Seeber, Stefan; Auer, Johannes; Koch, Stefan; Papadimitriou, Apollon

2013-01-01

The neonatal Fc receptor (FcRn) is important for the metabolic fate of IgG antibodies in vivo. Analysis of the interaction between FcRn and IgG in vitro might provide insight into the structural and functional integrity of therapeutic IgG that may affect pharmacokinetics (PK) in vivo. We developed a standardized pH gradient FcRn affinity liquid chromatography method with conditions closely resembling the physiological mechanism of interaction between IgG and FcRn. This method allows the separation of molecular IgG isoforms, degradation products and engineered molecules based on their affinity to FcRn. Human FcRn was immobilized on the column and a linear pH gradient from pH 5.5 to 8.8 was applied. FcRn chromatography was used in comparison to surface plasmon resonance to characterize different monoclonal IgG preparations, e.g., oxidized or aggregated species. Wild-type and engineered IgGs were compared in vitro by FcRn chromatography and in vivo by PK studies in huFcRn transgenic mice. Analytical FcRn chromatography allows differentiation of IgG samples and variants by peak pattern and retention time profile. The method can distinguish: 1) IgGs with different Fabs, 2) oxidized from native IgG, 3) aggregates from monomer and 4) antibodies with mutations in the Fc part from wild-type IgGs. Changes in the FcRn chromatographic behavior of mutant IgGs relative to the wild-type IgG correlate to changes in the PK profile in the FcRn transgenic mice. These results demonstrate that FcRn affinity chromatography is a useful new method for the assessment of IgG integrity. PMID:23765230

The affinity purification and characterization of ATP synthase complexes from mitochondria.

Science.gov (United States)

Runswick, Michael J; Bason, John V; Montgomery, Martin G; Robinson, Graham C; Fearnley, Ian M; Walker, John E

2013-02-13

The mitochondrial F₁-ATPase inhibitor protein, IF₁, inhibits the hydrolytic, but not the synthetic activity of the F-ATP synthase, and requires the hydrolysis of ATP to form the inhibited complex. In this complex, the α-helical inhibitory region of the bound IF₁ occupies a deep cleft in one of the three catalytic interfaces of the enzyme. Its N-terminal region penetrates into the central aqueous cavity of the enzyme and interacts with the γ-subunit in the enzyme's rotor. The intricacy of forming this complex and the binding mode of the inhibitor endow IF₁ with high specificity. This property has been exploited in the development of a highly selective affinity procedure for purifying the intact F-ATP synthase complex from mitochondria in a single chromatographic step by using inhibitor proteins with a C-terminal affinity tag. The inhibited complex was recovered with residues 1-60 of bovine IF₁ with a C-terminal green fluorescent protein followed by a His-tag, and the active enzyme with the same inhibitor with a C-terminal glutathione-S-transferase domain. The wide applicability of the procedure has been demonstrated by purifying the enzyme complex from bovine, ovine, porcine and yeast mitochondria. The subunit compositions of these complexes have been characterized. The catalytic properties of the bovine enzyme have been studied in detail. Its hydrolytic activity is sensitive to inhibition by oligomycin, and the enzyme is capable of synthesizing ATP in vesicles in which the proton-motive force is generated from light by bacteriorhodopsin. The coupled enzyme has been compared by limited trypsinolysis with uncoupled enzyme prepared by affinity chromatography. In the uncoupled enzyme, subunits of the enzyme's stator are degraded more rapidly than in the coupled enzyme, indicating that uncoupling involves significant structural changes in the stator region.

High affinity hemoglobin and Parkinson's disease.

Science.gov (United States)

Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

2014-12-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-abelian bosonization and higher spin symmetries

International Nuclear Information System (INIS)

Zaikov, R.P.

1995-03-01

The higher spin properties of the non-abelian bosonization in the classical theory are investigated. Both the symmetry transformation algebra and the classical current algebra for the non-abelian free fermionic model are linear Gel'fand-Dickey type algebras. However, for the corresponding WZNW model these algebras are different. There exist symmetry transformations which algebra remains the linear Gel'fand-Dickey algebra while in the corresponding current algebra nonlinear terms arised. Moreover, this algebra is closed (in Casimir form) only in an extended current space in which nonlinear currents are included. In the affine sector, it is necessary to include higher isotopic spin current too. As result we have have a triple extended algebra. (author). 30 refs

Providing affinity

DEFF Research Database (Denmark)

Guglielmi, Michel; Johannesen, Hl

2004-01-01

, Essex, Hertfordshire, Norfolk and Suffolk. Research found that there was a lack of identity or sense of belonging and nothing anchoring people to the region as a whole. Common affinity is somehow forced to the people of East England and thereby we came to the conclusion that a single landmark...... and potential situations but also virtual events that calls for an undeterminated process of resolution. This process is activated by the user who co-produces the actualisation as an answer to a virtual reality that we defined at the first place. The potential situations or the possible it is a fantomatic real....... The possible is like the real. It is determinated and it only lakes existence. While the possible is already made, the virtual is like a problematic which needs to be resolved and actualized. Our installations are based on high tech interactivity where we use sensors and remote communication to offer a sense...

Haemoglobin Pierre-Benite--a high affinity variant associated with relative polycythaemia.

Science.gov (United States)

Beard, M E; Potter, H C; Spearing, R L; Brennan, S O

2001-12-01

This is the second reported example of Hb Pierre--Benite (beta90 Glu-->Asp). This mutation is associated with increased oxygen affinity and polycythaemia. No instability was found and there was no charge shift detected by cellulose acetate electrophoresis at pH 8.3. The mutation was however, clearly indicated by electrospray ionization mass spectrometry (ESI MS), which showed an abnormal beta chain with a 14 Da decrease in mass. Blood volume studies documented a relative rather than a true polycythaemia and this finding has been reported in at least two other high affinity haemoglobin variants--Hb Heathrow and Hb Rahere. This finding led to delay in diagnosis because high oxygen affinity variants are conventionally considered to cause a true polycythaemia.

Will Bribery and Fraud Converge? Comparative Corruption in Higher Education in Russia and the USA

Science.gov (United States)

Osipian, Ararat L.

2014-01-01

This study analyses the issue of comparative corruption in the national higher education sectors in the United States of America (USA) and the Russian Federation (RF). Corruption in higher education, as well as the way it is addressed in legislation and court cases and reflected in the media, appears to be consistent with the trajectory and pace…

Proadifen-sensitive high affinity binding of 3H-alaproclate to liver membranes

International Nuclear Information System (INIS)

Ross, S.B.

1987-01-01

3 H-alaproclate, a selective 5 h ydroxytryptamine uptake inhibitor, was found to bind to microsomal membranes from the rat liver with high affinity (K D -=3 nM) and large capacity (B max about 2 nmol/g liver). This binding was stereoselective since S-( - )-alaproclate was 30 times more potent than the R-( + )-enantiomer to displace the 3 H-labelled racemate. Proadifen (SKF 525A), an inhibitor of cytochrome P-450, displaced the 3 H-alaproclate binding with the same, high affinity (K i =3 nM) as alaproclate itself. Repeated treatment with phenobarbital sodium (5x75 mg/kg intraperitoneally) increased the number of alaproclate binding sites 7-8 times without changing the affinity. However, most of the phenobarbital induced 3 H-alaproclate binding was not displaceable by proadifen, showing the presence of at least two different high affinity binding sites. The possible involvement of cytochrome P-450 in the alaproclate binding is discussed. (author)

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.

It's the peptide-MHC affinity, stupid.

Science.gov (United States)

Kammertoens, Thomas; Blankenstein, Thomas

2013-04-15

Adoptively transferred T cells can reject large established tumors, but recurrence due to escape variants frequently occurs. In this issue of Cancer Cell, Engels et al. demonstrate that the affinity of the target peptide to the MHC molecule determines whether large tumors will relapse following adoptive T cell therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Coupled Cluster Studies of Ionization Potentials and Electron Affinities of Single-Walled Carbon Nanotubes

Energy Technology Data Exchange (ETDEWEB)

Peng, Bo; Govind, Niranjan; Apra, Edoardo; Klemm, Michael; Hammond, Jeff R.; Kowalski, Karol

2017-02-03

In this paper we apply equation-of-motion coupled cluster (EOMCC) methods in studies of vertical ionization potentials (IP) and electron affinities (EA) for sin- gled walled carbon nanotubes. EOMCC formulations for ionization potentials and electron affinities employing excitation manifolds spanned by single and double ex- citations (IP/EA-EOMCCSD) are used to study IPs and EAs of nanotubes as a function of nanotube length. Several armchair nanotubes corresponding to C20nH20 models with n = 2 - 6 have been used in benchmark calculations. In agreement with previous studies, we demonstrate that the electronegativity of C20nH20 systems remains, to a large extent, independent of nanotube length. We also compare IP/EA- EOMCCSD results with those obtained with the coupled cluster models with single and double excitations corrected by perturbative triples, CCSD(T), and density func- tional theory (DFT) using global and range-separated hybrid exchange-correlation functionals.

Inhibitory GTP binding protein G/sub i/ regulates β-adrenoceptor affinity towards β-agonists

International Nuclear Information System (INIS)

Marbach, I.; Levitzki, A.

1987-01-01

Treatment of S-49 lymphoma cell membranes with pertussis toxin (PT) causes a three-fold reduction of β-adrenoceptor (βAR) affinity towards isoproterenol. A similar treatment with cholera toxin (CT) does not cause such a modulation. The effects were studied by the detailed analysis of 125 I-cyanopindolol (CYP) binding curves in the absence and presence of increasing agonist concentrations. Thus, the authors were able to compare in detail the effects of G/sub s/ and G/sub i/ on the agonist-associated state of the βAR. In contrast to these findings, PT treatment does not have any effect on the displacement of 125 I-CYP by (-)isoproterenol. These results demonstrate that the inhibitory GTP protein G/sub i/ modulates the βAR affinity towards β-agonists. This might be due to the association of G/sub i/ with the agonist-bound βAR x G/sub s/ x C complex within the membrane. This hypothesis, as well as others, is under investigation

Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.

Science.gov (United States)

Runge, Steffen; Schimmer, Susann; Oschmann, Jan; Schiødt, Christine Bruun; Knudsen, Sanne Möller; Jeppesen, Claus Bekker; Madsen, Kjeld; Lau, Jesper; Thøgersen, Henning; Rudolph, Rainer

2007-05-15

Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4.

Selective affinity labeling of a 27-kDa integral membrane protein in rat liver and kidney with N-bromoacetyl derivatives of L-thyroxine and 3,5,3'-triiodo-L-thyronine

International Nuclear Information System (INIS)

Koehrle, J.R.; Rasmussen, U.B.; Rokos, H.; Leonard, J.L.; Hesch, R.D.

1990-01-01

125I-Labeled N-bromoacetyl derivatives of L-thyroxine and L-triiodothyronine were used as alkylating affinity labels to identify rat liver and kidney microsomal membrane proteins which specifically bind thyroid hormones. Affinity label incorporation was analyzed by ethanol precipitation and individual affinity labeled proteins were identified by autoradiography after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Six to eight membrane proteins ranging in size from 17 to 84 kDa were affinity labeled by both bromoacetyl-L-thyroxine (BrAcT4) and bromoacetyl-L-triiodothyronine (BrAcT3). Affinity labeling was time- and temperature-dependent, and both reduced dithiols and detergents increased affinity labeling, predominantly in a 27-kDa protein(s). Up to 80% of the affinity label was associated with a 27-kDa protein (p27) under optimal conditions. Affinity labeling of p27 by 0.4 nM BrAc[125I]L-T4 was blocked by 0.1 microM of the alkylating ligands BrAcT4, BrAcT3, or 100 microM iodoacetate, by 10 microM concentrations of the non-alkylating, reversible ligands N-acetyl-L-thyroxine, 3,3',5'-triiodothyronine, 3,5-diiodosalicylate, and EMD 21388, a T4-antagonistic flavonoid. Neither 10 microM L-T4, nor 10 microM N-acetyltriiodothyronine or 10 microM L-triiodothyronine blocked affinity labeling of p27 or other affinity labeled bands. Affinity labeling of a 17-kDa band was partially inhibited by excess of the alkylating ligands BrAcT4, BrAcT3, and iodoacetate, but labeling of other minor bands was not blocked by excess of the competitors. BrAc[125I]T4 yielded higher affinity label incorporation than BrAc[125I]T3, although similar banding patterns were observed, except that BrAcT3 affinity labeled more intensely a 58,000-Da band in liver and a 53,000-55,000-Da band in kidney

Elastic models: a comparative study applied to retinal images.

Science.gov (United States)

Karali, E; Lambropoulou, S; Koutsouris, D

2011-01-01

In this work various methods of parametric elastic models are compared, namely the classical snake, the gradient vector field snake (GVF snake) and the topology-adaptive snake (t-snake), as well as the method of self-affine mapping system as an alternative to elastic models. We also give a brief overview of the methods used. The self-affine mapping system is implemented using an adapting scheme and minimum distance as optimization criterion, which is more suitable for weak edges detection. All methods are applied to glaucomatic retinal images with the purpose of segmenting the optical disk. The methods are compared in terms of segmentation accuracy and speed, as these are derived from cross-correlation coefficients between real and algorithm extracted contours and segmentation time, respectively. As a result, the method of self-affine mapping system presents adequate segmentation time and segmentation accuracy, and significant independence from initialization.

Color and Contrast Enhancement by Controlled Piecewise Affine Histogram Equalization

Directory of Open Access Journals (Sweden)

Jose-Luis Lisani

2012-10-01

Full Text Available This paper presents a simple contrast enhancement algorithm based on histogram equalization (HE. The proposed algorithm performs a piecewise affine transform of the intensity levels of a digital image such that the new cumulative distribution function will be approximately uniform (as with HE, but where the stretching of the range is locally controlled to avoid brutal noise enhancement. We call this algorithm Piecewise Affine Equalization (PAE. Several experiments show that, in general, the new algorithm improves HE results.

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

International Nuclear Information System (INIS)

Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N.; Moran, Jeffery H.; Prather, Paul L.

2013-01-01

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB 1 Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB 2 Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB 2 Rs (hCB 2 Rs). The affinity of cannabinoids for hCB 2 Rs was determined by competition binding studies employing CHO-hCB 2 membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB 2 cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB 2 Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB 2 Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ 9 -tetrahydrocannabinol (Δ 9 -THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB 2 R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB 2 Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB 2 Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB 1 and CB 2 Rs. - Highlights: • JWH-018 and JWH-073 are synthetic cannabinoids present in abused K2

Affinity fluorescence-labeled peptides for the early detection of cancer in Barrett's esophagus

Science.gov (United States)

Li, Meng; Lu, Shaoying; Piraka, Cyrus; Appelman, Henry; Kwon, Rich; Soetikno, Roy; Kaltenbach, Tonya; Wang, Thomas D.

2009-02-01

Fluorescence-labeled peptides that affinity bind to neoplastic mucsosa are promising for use as a specific contrast agent in the detection of pre-malignant tissue in the esophagus. This method is can be used to identify expression of biological markers associated with dysplasia on endoscopic imaging as a guide for biopsy and represents a novel method for the early detection and prevention of cancer. We demonstrate the use of phage display to select affinity peptides and identify the sequence "ASYNYDA" that binds with high target-to-background ratio to dysplastic esophageal mucosa compared to that of intestinal metaplasia. Validation of preferential binding is demonstrated for neoplasia in the setting of Barrett's esophagus. An optimal tradeoff between sensitivity and specificity of 82% and 85% was found at the relative threshold of 0.60 with a target-to-background ratio of 1.81 and an area under the ROC curve of 0.87. Peptides are a novel class of ligand for targeted detection of pre-malignant mucosa for purposes of screening and surveillance.

Affine Kac-Moody algebras and their representations

International Nuclear Information System (INIS)

Slansky, R.

1988-01-01

Highest weight representation theory of finite dimensional and affine Kac-Moody algebras is summarized from a unified point of view. Lattices of discrete additive quantum numbers and the presentation of Lie algebras on Cartan matrices are the central points of departure for the analysis. (author)

Affinity monolith chromatography: A review of general principles and applications.

Science.gov (United States)

Li, Zhao; Rodriguez, Elliott; Azaria, Shiden; Pekarek, Allegra; Hage, David S

2017-11-01

Affinity monolith chromatography, or AMC, is a liquid chromatographic method in which the support is a monolith and the stationary phase is a biological-binding agent or related mimic. AMC has become popular for the isolation of biochemicals, for the measurement of various analytes, and for studying biological interactions. This review will examine the principles and applications of AMC. The materials that have been used to prepare AMC columns will be discussed, which have included various organic polymers, silica, agarose, and cryogels. Immobilization schemes that have been used in AMC will also be considered. Various binding agents and applications that have been reported for AMC will then be described. These applications will include the use of AMC for bioaffinity chromatography, immunoaffinity chromatography, dye-ligand affinity chromatography, and immobilized metal-ion affinity chromatography. The use of AMC with chiral stationary phases and as a tool to characterize biological interactions will also be examined. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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...... (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...... 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....

Lie algebraic discussion for affinity based information diffusion in social networks

Science.gov (United States)

Shang, Yilun

2017-11-01

In this paper we develop a dynamical information diffusion model which features the affinity of people with information disseminated in social networks. Four types of agents, i.e., susceptible, informed, known, and refractory ones, are involved in the system, and the affinity mechanism composing of an affinity threshold which represents the fitness of information to be propagated is incorporated. The model can be generally described by a time-inhomogeneous Markov chain, which is governed by its master (Kolmogorov) equation. Based on the Wei-Norman method, we derive analytical solutions of the model by constructing a low-dimensional Lie algebra. Numerical examples are provided to illustrate the obtained theoretical results. This study provides useful insights into the closed-form solutions of complex social dynamics models through the Lie algebra method.

Development of an affinity-matured humanized anti-epidermal growth factor receptor antibody for cancer immunotherapy.

Science.gov (United States)

Nakanishi, Takeshi; Maru, Takamitsu; Tahara, Kazuhiro; Sanada, Hideaki; Umetsu, Mitsuo; Asano, Ryutaro; Kumagai, Izumi

2013-02-01

We showed previously that humanization of 528, a murine anti-epidermal growth factor receptor (EGFR) antibody, causes reduced affinity for its target. Here, to improve the affinity of the humanized antibody for use in cancer immunotherapy, we constructed phage display libraries focused on the complementarity-determining regions (CDRs) of the antibody and carried out affinity selection. Two-step selections using libraries constructed in a stepwise manner enabled a 32-fold affinity enhancement of humanized 528 (h528). Thermodynamic analysis of the interactions between the variable domain fragment of h528 (h528Fv) mutants and the soluble extracellular domain of EGFR indicated that the h528Fv mutants obtained from the first selection showed a large increase in negative enthalpy change due to binding, resulting in affinity enhancement. Furthermore, mutants from the second selection showed a decrease in entropy loss, which led to further affinity maturation. These results suggest that a single mutation in the heavy chain variable domain (i.e. Tyr(52) to Trp) enthalpically contributed for overcoming the energetic barrier to the antigen-antibody interaction, which was a major hurdle for the in vitro affinity maturation of h528. We reported previously that the humanized bispecific diabody hEx3 Db, which targets EGFR and CD3, shows strong anti-tumor activity. hEx3 Db mutants, in which the variable domains of h528 were replaced with those of the affinity-enhanced mutants, were prepared and characterized. In a growth inhibition assay of tumor cells, the hEx3 Db mutants showed stronger anti-tumor activity than that of hEx3 Db, suggesting that affinity enhancement of h528Fv enhances the anti-tumor activity of the bispecific diabody.

Dynamics of Inequalities in Access to Higher Education: Bulgaria in a Comparative Perspective

Science.gov (United States)

Ilieva-Trichkova, Petya; Boyadjieva, Pepka

2014-01-01

This paper aims at studying the dynamics of inequalities in access to higher education (HE) both in a historical and a comparative perspective. It uses Bulgaria as a case study and places it among five other countries such as Estonia, Hungary, Poland, Slovakia and Slovenia. The adopted approach differentiates between equity in HE and inequalities…

Interaction of albumins and heparinoids investigated by affinity capillary electrophoresis and free flow electrophoresis.

Science.gov (United States)

Mozafari, Mona; El Deeb, Sami; Krull, Friederike; Wildgruber, Robert; Weber, Gerhard; Reiter, Christian G; Wätzig, Hermann

2018-02-01

A fast and precise affinity capillary electrophoresis (ACE) method has been applied to investigate the interactions between two serum albumins (HSA and BSA) and heparinoids. Furthermore, different free flow electrophoresis methods were developed to separate the species which appears owing to interaction of albumins with pentosan polysulfate sodium (PPS) under different experimental conditions. For ACE experiments, the normalized mobility ratios (∆R/R f ), which provided information about the binding strength and the overall charge of the protein-ligand complex, were used to evaluate the binding affinities. ACE experiments were performed at two different temperatures (23 and 37°C). Both BSA and HSA interact more strongly with PPS than with unfractionated and low molecular weight heparins. For PPS, the interactions can already be observed at low mg/L concentrations (3 mg/L), and saturation is already obtained at approximately 20 mg/L. Unfractionated heparin showed almost no interactions with BSA at 23°C, but weak interactions at 37°C at higher heparin concentrations. The additional signals also appeared at higher concentrations at 37°C. Nevertheless, in most cases the binding data were similar at both temperatures. Furthermore, HSA showed a characteristic splitting in two peaks especially after interacting with PPS, which is probably attributable to the formation of two species or conformational change of HSA after interacting with PPS. The free flow electrophoresis methods have confirmed and completed the ACE experiments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High affinity calmodulin target sequence in the signalling molecule PI 3-kinase

DEFF Research Database (Denmark)

Fischer, R; Julsgart, J; Berchtold, M W

1998-01-01

M-binding peptide derived from the p110gamma isoform interacts with CaM in a calcium-dependent way. Using gel shift analysis and fluorescence spectrophotometry we discovered that the peptide forms a high affinity complex with CaM. Titration experiments using dansylated CaM gave an affinity constant of 5 n...

Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life Extension.

Science.gov (United States)

Fan, Kelong; Jiang, Bing; Guan, Zhe; He, Jiuyang; Yang, Dongling; Xie, Ni; Nie, Guohui; Xie, Can; Yan, Xiyun

2018-04-10

Nanobodies consist of a single domain variable fragment of a camelid heavy-chain antibody. Nanobodies have potential applications in biomedical fields because of their simple production procedures and low cost. Occasionally, nanobody clones of interest exhibit low affinities for their target antigens, which, together with their short half-life limit bioanalytical or therapeutic applications. Here, we developed a novel platform we named fenobody, in which a nanobody developed against H5N1 virus is displayed on the surface of ferritin in the form of a 24mer. We constructed a fenobody by substituting the fifth helix of ferritin with the nanobody. TEM analysis showed that nanobodies were displayed on the surface of ferritin in the form of 6 × 4 bundles, and that these clustered nanobodies are flexible for antigen binding in spatial structure. Comparing fenobodies with conventional nanobodies currently used revealed that the antigen binding apparent affinity of anti-H5N1 fenobody was dramatically increased (∼360-fold). Crucially, their half-life extension in a murine model was 10-fold longer than anti-H5N1 nanobody. In addition, we found that our fenobodies are highly expressed in Escherichia coli, and are both soluble and thermo-stable nanocages that self-assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies have unique advantages over currently available systems for apparent affinity enhancement and half-life extension of nanobodies. Our fenobody system presents a suitable platform for various large-scale biotechnological processes and should greatly facilitate the application of nanobody technology in these areas.

The N-terminal domain determines the affinity and specificity of H1 binding to chromatin

International Nuclear Information System (INIS)

Öberg, Christine; Belikov, Sergey

2012-01-01

Highlights: ► wt Human histone H1.4 and hH1.4 devoid of N-terminal domain, ΔN-hH1.4, were compared. ► Both histones bind to chromatin, however, ΔN-hH1.4 displays lower binding affinity. ► Interaction of ΔN-hH1.4 with chromatin includes a significant unspecific component. ► N-terminal domain is a determinant of specificity of histone H1 binding to chromatin. -- Abstract: Linker histone H1, one of the most abundant nuclear proteins in multicellular eukaryotes, is a key component of the chromatin structure mainly due to its role in the formation and maintenance of the 30 nm chromatin fiber. It has a three-domain structure; a central globular domain flanked by a short N-terminal domain and a long, highly basic C-terminal domain. Previous studies have shown that the binding abilities of H1 are at large determined by the properties of the C-terminal domain; much less attention has been paid to role of the N-terminal domain. We have previously shown that H1 can be reconstituted via cytoplasmic mRNA injection in Xenopus oocytes, cells that lack somatic H1. The heterologously expressed H1 proteins are incorporated into in vivo assembled chromatin at specific sites and the binding event is monitored as an increase in nucleosomal repeat length (NRL). Using this setup we have here compared the binding properties of wt-H1.4 and hH1.4 devoid of its N-terminal domain (ΔN-hH1.4). The ΔN-hH1.4 displays a drastically lower affinity for chromatin binding as compared to the wild type hH1.4. Our data also indicates that ΔN-hH1.4 is more prone to unspecific chromatin binding than the wild type. We conclude that the N-terminal domain of H1 is an important determinant of affinity and specificity of H1-chromatin interactions.

Approximate convex hull of affine iterated function system attractors

International Nuclear Information System (INIS)

Mishkinis, Anton; Gentil, Christian; Lanquetin, Sandrine; Sokolov, Dmitry

2012-01-01

Highlights: ► We present an iterative algorithm to approximate affine IFS attractor convex hull. ► Elimination of the interior points significantly reduces the complexity. ► To optimize calculations, we merge the convex hull images at each iteration. ► Approximation by ellipses increases speed of convergence to the exact convex hull. ► We present a method of the output convex hull simplification. - Abstract: In this paper, we present an algorithm to construct an approximate convex hull of the attractors of an affine iterated function system (IFS). We construct a sequence of convex hull approximations for any required precision using the self-similarity property of the attractor in order to optimize calculations. Due to the affine properties of IFS transformations, the number of points considered in the construction is reduced. The time complexity of our algorithm is a linear function of the number of iterations and the number of points in the output approximate convex hull. The number of iterations and the execution time increases logarithmically with increasing accuracy. In addition, we introduce a method to simplify the approximate convex hull without loss of accuracy.

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

Science.gov (United States)

de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

2016-01-01

Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter

DEFF Research Database (Denmark)

Zhang, Peng; Jørgensen, Trine Nygaard; Løland, Claus Juul

2013-01-01

A novel fluorescent ligand was synthesized as a high-affinity, high specificity probe for visualizing the serotonin transporter (SERT). The rhodamine fluorophore was extended from an aniline substitution on the 5-position of the dihydroisobenzofuran ring of citalopram (2, 1-(3-(dimethylamino......)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile), using an ethylamino linker. The resulting rhodamine-labeled ligand 8 inhibited [3H]5-HT uptake in COS-7 cells (Ki = 225 nM) with similar potency to the tropane-based JHC 1-064 (1), but with higher specificity towards the SERT relative...

Aspects of affine Toda field theory

International Nuclear Information System (INIS)

Braden, H.W.; Corrigan, E.; Dorey, P.E.; Sasaki, R.

1990-05-01

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 E 8 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.)

Extreme disorder in an ultrahigh-affinity protein complex

DEFF Research Database (Denmark)

Borgia, Alessandro; Borgia, Madeleine B; Bugge, Katrine

2018-01-01

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions...... with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring...... or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex...

VP24-Karyopherin Alpha Binding Affinities Differ between Ebolavirus Species, Influencing Interferon Inhibition and VP24 Stability.

Science.gov (United States)

Schwarz, Toni M; Edwards, Megan R; Diederichs, Audrey; Alinger, Joshua B; Leung, Daisy W; Amarasinghe, Gaya K; Basler, Christopher F

2017-02-15

Zaire ebolavirus (EBOV), Bundibugyo ebolavirus (BDBV), and Reston ebolavirus (RESTV) belong to the same genus but exhibit different virulence properties. VP24 protein, a structural protein present in all family members, blocks interferon (IFN) signaling and likely contributes to virulence. Inhibition of IFN signaling by EBOV VP24 (eVP24) involves its interaction with the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear transporters. Here, we evaluated eVP24, BDBV VP24 (bVP24), and RESTV VP24 (rVP24) interactions with three NPI-1 subfamily KPNAs (KPNA1, KPNA5, and KPNA6). Using purified proteins, we demonstrated that each VP24 binds to each of the three NPI-1 KPNAs. bVP24, however, exhibited approximately 10-fold-lower KPNA binding affinity than either eVP24 or rVP24. Cell-based assays also indicate that bVP24 exhibits decreased KPNA interaction, decreased suppression of IFN induced gene expression, and a decreased half-life in transfected cells compared to eVP24 or rVP24. Amino acid sequence alignments between bVP24 and eVP24 also identified residues within and surrounding the previously defined eVP24-KPNA5 binding interface that decrease eVP24-KPNA affinity or bVP24-KPNA affinity. VP24 mutations that lead to reduced KPNA binding affinity also decrease IFN inhibition and shorten VP24 half-lives. These data identify novel functional differences in VP24-KPNA interaction and reveal a novel impact of the VP24-KPNA interaction on VP24 stability. The interaction of Ebola virus (EBOV) VP24 protein with host karyopherin alpha (KPNA) proteins blocks type I interferon (IFN) signaling, which is a central component of the host innate immune response to viral infection. Here, we quantitatively compared the interactions of VP24 proteins from EBOV and two members of the Ebolavirus genus, Bundibugyo virus (BDBV) and Reston virus (RESTV). The data reveal lower binding affinity of the BDBV VP24 (bVP24) for KPNAs and demonstrate that the interaction with KPNA modulates inhibition

The monoclonal S9.6 antibody exhibits highly variable binding affinities towards different R-loop sequences.

Directory of Open Access Journals (Sweden)

Fabian König

Full Text Available The monoclonal antibody S9.6 is a widely-used tool to purify, analyse and quantify R-loop structures in cells. A previous study using the surface plasmon resonance technology and a single-chain variable fragment (scFv of S9.6 showed high affinity (0.6 nM for DNA-RNA and also a high affinity (2.7 nM for RNA-RNA hybrids. We used the microscale thermophoresis method allowing surface independent interaction studies and electromobility shift assays to evaluate additional RNA-DNA hybrid sequences and to quantify the binding affinities of the S9.6 antibody with respect to distinct sequences and their GC-content. Our results confirm high affinity binding to previously analysed sequences, but reveals that binding affinities are highly sequence specific. Our study presents R-loop sequences that independent of GC-content and in different sequence variations exhibit either no binding, binding affinities in the micromolar range and as well high affinity binding in the nanomolar range. Our study questions the usefulness of the S9.6 antibody in the quantitative analysis of R-loop sequences in vivo.

Low uptake affinity cultivars with biochar to tackle Cd-tainted rice — A field study over four rice seasons in Hunan, China

Energy Technology Data Exchange (ETDEWEB)

Chen, De; Guo, Hu; Li, Ruiyue [Institute of Resources, Ecosystem and Environment of Agriculture, and Center of Biochar and Green Agriculture, Nanjing Agricultural University, 1 Weigang, Nanjing 210095 (China); Li, Lianqing, E-mail: lqli@njau.edu.cn [Institute of Resources, Ecosystem and Environment of Agriculture, and Center of Biochar and Green Agriculture, Nanjing Agricultural University, 1 Weigang, Nanjing 210095 (China); Pan, Genxing [Institute of Resources, Ecosystem and Environment of Agriculture, and Center of Biochar and Green Agriculture, Nanjing Agricultural University, 1 Weigang, Nanjing 210095 (China); Chang, Andrew [Department of Environmental Sciences, University of California, Riverside, CA 92521 (United States); Joseph, Stephen [Institute of Resources, Ecosystem and Environment of Agriculture, and Center of Biochar and Green Agriculture, Nanjing Agricultural University, 1 Weigang, Nanjing 210095 (China); School of Materials Science and Engineering, University of New South Wales, Sydney, NSW 2052 (Australia)

2016-01-15

Biochar is becoming an environmentally friendly material for remediation of heavy metal contaminated soils and improving food safety. A field trial over four rice seasons was conducted to investigate the use of biochar and low Cd accumulating cultivars on Cd uptake in a heavy metal contaminated soil. Wheat straw derived biochar was applied at 0, 20 and 40 t ha{sup −1}. Two rice cultivars with differing Cd accumulation abilities were selected in each season. The results showed that both biochar and low Cd affinity cultivars significantly reduced rice grain Cd accumulation. Biochar had no significant effect the first season but thereafter consistently reduced rice grain Cd by a maximum of 61, 86 and 57% over the next three seasons. Zn accumulation in the rice grains was not decreased by biochar application, although available soil Zn was sharply reduced (35–91%). Indica conventional rice cultivars had much lower Cd, but higher Zn and lower Cd/Zn ratios in the grain than indica hybrid cultivars. Biochar was more effective for mitigating grain Cd accumulation in low Cd affinity cultivars than in high affinity cultivars. Soil pH was sustainably increased (up to nearly 1 unit) while available Cd significantly decreased by a maximum of 85% after biochar addition. The translocation of Cd from rice roots to shoots was reduced from 20 to 80% by biochar. Low uptake affinity cultivars combined with biochar reduced late rice grain Cd concentration and Cd/Zn ratios by 69–80% and 72–80%, respectively. It indicated that the management of combining biochar and low Cd affinity cultivars should be an efficient way to remediate Cd contaminated rice paddies and reduce health risk associated with consuming rice from these soils. - Highlights: • Biochar sustainably reduced soil Cd availability and Cd translocation in rice plant. • Indica conventional cultivars had lower Cd but higher Zn in grains than hybrid ones. • Biochar significantly reduced grain Cd and Cd/Zn ratio

Ceramide content is higher in type I compared to type II fibers in obesity and type 2 diabetes mellitus

DEFF Research Database (Denmark)

Kristensen, Ditte Bech; Prats Gavalda, Clara; Larsen, Steen

2012-01-01

This study investigated fiber-type-specific muscle ceramide content in obese subjects and type 2 diabetes patients. Two substudies, one which compared type 2 diabetes patients to both lean- and obese BMI-matched subjects and the other study which compared lean body-matched post-obese, obese......, and control subjects, were performed. A fasting blood sample was obtained and plasma insulin and glucose determined. A muscle biopsy was obtained from deltoideus and vastus lateralis, and fiber-type ceramide content was determined by fluorescence immunohistochemistry. Insulin sensitivity estimated by Quicki...... index was higher in lean compared to type 2 diabetes patients and obese controls. Also in control and post-obese subjects, a higher insulin sensitivity was observed compared to obese subjects. Ceramide content was consistently higher in type I than in type II muscle fibers and higher in deltoideus than...

A rapid solution-based method for determining the affinity of heroin hapten-induced antibodies to heroin, its metabolites, and other opioids.

Science.gov (United States)

Torres, Oscar B; Duval, Alexander J; Sulima, Agnieszka; Antoline, Joshua F G; Jacobson, Arthur E; Rice, Kenner C; Alving, Carl R; Matyas, Gary R

2018-06-01

We describe for the first time a method that utilizes microscale thermophoresis (MST) technology to determine polyclonal antibody affinities to small molecules. Using a novel type of heterologous MST, we have accurately measured a solution-based binding affinity of serum antibodies to heroin which was previously impossible with other currently available methods. Moreover, this mismatch approach (i.e., using a cross-reactive hapten tracer) has never been reported in the literature. When compared with equilibrium dialysis combined with ultra-performance liquid chromatography/tandem mass spectrometry (ED-UPLC/MS/MS), this novel MST method yields similar binding affinity values for polyclonal antibodies to the major heroin metabolites 6-AM and morphine. Additionally, we herein report the method of synthesis of this novel cross-reactive hapten, MorHap-acetamide-a useful analog for the study of heroin hapten-antibody interactions. Using heterologous MST, we were able to determine the affinities, down to nanomolar accuracies, of polyclonal antibodies to various abused opioids. While optimizing this method, we further discovered that heroin is protected from serum esterase degradation by the presence of these antibodies in a concentration-dependent manner. Lastly, using affinity data for a number of structurally different opioids, we were able to dissect the moieties that are crucial to antibody binding. The novel MST method that is presented herein can be extended to the analysis of any ligand that is prone to degradation and can be applied not only to the development of vaccines to substances of abuse but also to the analysis of small molecule/protein interactions in the presence of serum. Graphical abstract Strategy for the determination of hapten-induced antibody affinities using Microscale thermophoresis.

Ultrasound elastography: efficient estimation of tissue displacement using an affine transformation model

Science.gov (United States)

Hashemi, Hoda Sadat; Boily, Mathieu; Martineau, Paul A.; Rivaz, Hassan

2017-03-01

Ultrasound elastography entails imaging mechanical properties of tissue and is therefore of significant clinical importance. In elastography, two frames of radio-frequency (RF) ultrasound data that are obtained while the tissue is undergoing deformation, and the time-delay estimate (TDE) between the two frames is used to infer mechanical properties of tissue. TDE is a critical step in elastography, and is challenging due to noise and signal decorrelation. This paper presents a novel and robust technique TDE using all samples of RF data simultaneously. We assume tissue deformation can be approximated by an affine transformation, and hence call our method ATME (Affine Transformation Model Elastography). The affine transformation model is utilized to obtain initial estimates of axial and lateral displacement fields. The affine transformation only has six degrees of freedom (DOF), and as such, can be efficiently estimated. A nonlinear cost function that incorporates similarity of RF data intensity and prior information of displacement continuity is formulated to fine-tune the initial affine deformation field. Optimization of this function involves searching for TDE of all samples of the RF data. The optimization problem is converted to a sparse linear system of equations, which can be solved in real-time. Results on simulation are presented for validation. We further collect RF data from in-vivo patellar tendon and medial collateral ligament (MCL), and show that ATME can be used to accurately track tissue displacement.

Self-affine fractal growth front of Aspergillus oryzae

Science.gov (United States)

Matsuura, Shu; Miyazima, Sasuke

1992-12-01

Aspergillus oryzae have been grown in various environmental conditions and analyzed from the viewpoint of self-affinity. The growth behavior can be described by the Eden model in favorable conditions, and by DLA in unfavorable conditions.

New inorganic (an)ion exchangers with a higher affinity for arsenate and a competitive removal capacity towards fluoride, bromate, bromide, selenate, selenite, arsenite and borate

KAUST Repository

Chubar, Natalia

2011-12-01

Highly selective materials and effective technologies are needed to meet the increasingly stronger drinking water standards for targeted ionic species. Inorganic ion exchangers based on individual and mixed-metal hydrous oxides (or mixed adsorbents that contain inorganic ion exchangers in their composition) are adsorptive materials that are capable of lowering the concentrations of anionic contaminants, such as H 2AsO 4 -, H 3AsO 3, F -, Br -, BrO 3 -, HSeO 4 -, HSeO 3 - and H 3BO 3, to 10 μg/L or less. To achieve a higher selectivity towards arsenate, a new ion exchanger based on Mg-Al hydrous oxides was developed by a novel, cost-effective and environmentally friendly synthesis method via a non-traditional (alkoxide-free) sol-gel approach. The exceptional adsorptive capacity of the Mg-Al hydrous oxides towards H 2AsO 4 - (up to 200 mg[As]/gdw) is due to the high affinity of this sorbent towards arsenate (steep equilibrium isotherms) and its fast adsorption kinetics. Because of the mesoporous (as determined by N 2 adsorption and SEM) and layered (as determined by XRD and FTIR) structure of the ion-exchange material as well as the abundance of anion exchange sites (as determined by XPS and potentiometric titration) on its surface the material demonstrated very competitive (or very high) removal capacity towards other targeted anions, including fluoride, bromide, bromate, selenate, selenite, and borate. © 2011 IWA Publishing.

Poly(hydroxyethyl methacrylate) based affinity membranes for in vitro removal of anti-dsDNA antibodies from SLE plasma.

Science.gov (United States)

Uzun, Lokman; Yavuz, Handan; Osman, Bilgen; Celik, Hamdi; Denizli, Adil

2010-07-01

The preparation of polymeric membrane using affinity technology for application in blood filtration devices is described here. DNA attached poly(hydroxyethyl methacrylate) (PHEMA) based microporous affinity membrane was prepared for selective removal of anti-dsDNA antibodies from systemic lupus erythematosus (SLE) patient plasma in in vitro. In order to further increase blood-compatibility of affinity membrane, aminoacid based comonomer N-methacryloyl-L-alanine (MAAL) was included in the polymerization recipe. PHEMAAL membrane was produced by a photopolymerization technique and then characterized by swelling tests and scanning electron microscope (SEM) studies. Blood-compatibility tests were also performed. The water swelling ratio of PHEMAAL membrane increased significantly (133.2%) compared with PHEMA (58%). PHEMAAL membrane has large pores around in the range of 5-10 microm. All the clotting times increased when compared with PHEMA membrane. Loss of platelets and leukocytes was very low. DNA loading was 7.8 mg/g. There was a very low anti-dsDNA-antibody adsorption onto the plain PHEMAAL membrane, about 78 IU/g. The PHEMAAL-DNA membrane adsorbed anti-dsDNA-antibody in the range of 10-68 x 10(3)IU/g from SLE plasma. Anti-dsDNA-antibody concentration decreased significantly from 875 to 144 IU/ml with the time. Anti-dsDNA-antibodies could be repeatedly adsorbed and eluted without noticeable loss in the anti-dsDNA-antibody adsorption amount. (c) 2010 Elsevier B.V. All rights reserved.

Detection of Hepatitis C core antibody by dual-affinity yeast chimera and smartphone-based electrochemical sensing.

Science.gov (United States)

Aronoff-Spencer, Eliah; Venkatesh, A G; Sun, Alex; Brickner, Howard; Looney, David; Hall, Drew A

2016-12-15

Yeast cell lines were genetically engineered to display Hepatitis C virus (HCV) core antigen linked to gold binding peptide (GBP) as a dual-affinity biobrick chimera. These multifunctional yeast cells adhere to the gold sensor surface while simultaneously acting as a "renewable" capture reagent for anti-HCV core antibody. This streamlined functionalization and detection strategy removes the need for traditional purification and immobilization techniques. With this biobrick construct, both optical and electrochemical immunoassays were developed. The optical immunoassays demonstrated detection of anti-HCV core antibody down to 12.3pM concentrations while the electrochemical assay demonstrated higher binding constants and dynamic range. The electrochemical format and a custom, low-cost smartphone-based potentiostat ($20 USD) yielded comparable results to assays performed on a state-of-the-art electrochemical workstation. We propose this combination of synthetic biology and scalable, point-of-care sensing has potential to provide low-cost, cutting edge diagnostic capability for many pathogens in a variety of settings. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of CH/π interactions in the high affinity binding of streptavidin and biotin.

Science.gov (United States)

Ozawa, Motoyasu; Ozawa, Tomonaga; Nishio, Motohiro; Ueda, Kazuyoshi

2017-08-01

The streptavidin-biotin complex has an extraordinarily high affinity (Ka: 10 15 mol -1 ) and contains one of the strongest non-covalent interactions known. This strong interaction is widely used in biological tools, including for affinity tags, detection, and immobilization of proteins. Although hydrogen bond networks and hydrophobic interactions have been proposed to explain this high affinity, the reasons for it remain poorly understood. Inspired by the deceased affinity of biotin observed for point mutations of streptavidin at tryptophan residues, we hypothesized that a CH/π interaction may also contribute to the strong interaction between streptavidin and biotin. CH/π interactions were explored and analyzed at the biotin-binding site and at the interface of the subunits by the fragment molecular orbital method (FMO) and extended applications: PIEDA and FMO4. The results show that CH/π interactions are involved in the high affinity for biotin at the binding site of streptavidin. We further suggest that the involvement of CH/π interactions at the subunit interfaces and an extended CH/π network play more critical roles in determining the high affinity, rather than involvement at the binding site. Copyright © 2017 Elsevier Inc. All rights reserved.

Atrazine Molecular Imprinted Polymers: Comparative Analysis by Far-Infrared and Ultraviolet Induced Polymerization

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Jun Chen

2014-01-01

Full Text Available Atrazine molecular imprinted polymers (MIPs were comparatively synthesized using identical polymer formulation by far-infrared (FIR radiation and ultraviolet (UV-induced polymerization, respectively. Equilibrium binding experiments were carried out with the prepared MIPs; the results showed that MIPuv possessed specific binding to atrazine compared with their MIPFIR radiation counterparts. Scatchard plot’s of both MIPs indicated that the affinities of the binding sites in MIPs are heterogeneous and can be approximated by two dissociation-constants corresponding to the high- and low-affinity binding sites. Moreover, several common pesticides including atrazine, cyromazine, metamitron, simazine, ametryn, terbutryn were tested to determine their specificity, similar imprinting factor (IF and different selectivity index (SI for both MIPs. Physical characterization of the polymers revealed that the different polymerization methods led to slight differences in polymer structures and performance by scanning electron microscope (SEM, Fourier transform infrared absorption (FT-IR, and mercury analyzer (MA. Finally, both MIPs were used as selective sorbents for solid phase extraction (SPE of atrazine from lake water, followed by high performance liquid chromatography (HPLC analysis. Compared with commercial C18 SPE sorbent (86.4%–94.8%, higher recoveries of atrazine in spiked lake water were obtained in the range of 90.1%–97.1% and 94.4%–101.9%, for both MIPs, respectively.

Novel nonphosphorylated peptides with conserved sequences selectively bind to Grb7 SH2 domain with affinity comparable to its phosphorylated ligand.

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Dan Zhang

Full Text Available The Grb7 (growth factor receptor-bound 7 protein, a member of the Grb7 protein family, is found to be highly expressed in such metastatic tumors as breast cancer, esophageal cancer, liver cancer, etc. The src-homology 2 (SH2 domain in the C-terminus is reported to be mainly involved in Grb7 signaling pathways. Using the random peptide library, we identified a series of Grb7 SH2 domain-binding nonphosphorylated peptides in the yeast two-hybrid system. These peptides have a conserved GIPT/K/N sequence at the N-terminus and G/WD/IP at the C-terminus, and the region between the N-and C-terminus contains fifteen amino acids enriched with serines, threonines and prolines. The association between the nonphosphorylated peptides and the Grb7 SH2 domain occurred in vitro and ex vivo. When competing for binding to the Grb7 SH2 domain in a complex, one synthesized nonphosphorylated ligand, containing the twenty-two amino acid-motif sequence, showed at least comparable affinity to the phosphorylated ligand of ErbB3 in vitro, and its overexpression inhibited the proliferation of SK-BR-3 cells. Such nonphosphorylated peptides may be useful for rational design of drugs targeted against cancers that express high levels of Grb7 protein.

The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

Directory of Open Access Journals (Sweden)

Bryan L Roth

Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

Congruence of genomic and ethnolinguistic affinities among five ...

Indian Academy of Sciences (India)

their ethnic and linguistic affinities, we analysed DNA samples of individuals drawn from five tribes with diverse, but ... arisen from admixture between the Gonds (maternal) and ..... nuclear `fossil' of the mitochondrial D-loop and the origin of.

Lapa vermelha IV Hominid 1: morphological affinities of the earliest known American

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Neves Walter A.

1999-01-01

Full Text Available Several studies concerning the extra-continental morphological affinities of Paleo-Indian skeletons, carried out independently in South and North America, have indicated that the Americas were first occupied by non-Mongoloids that made their way to the New World through the Bering Strait in ancient times. The first South Americans show a clear resemblance to modern South Pacific and African populations, while the first North Americans seem to be at an unresolved morphological position between modern South Pacific and Europeans. In none of these analyses the first Americans show any resemblance to either northeast Asians or modern native Americans. So far, these studies have included affirmed and putative early skeletons thought to date between 8,000 and 10,000 years B.P. In this work the extra-continental morphological affinities of a Paleo-Indian skeleton well dated between 11,000 and 11,500 years B.P. (Lapa Vermelha IV Hominid 1, or "Luzia" is investigated, using as comparative samples Howells' (1989 world-wide modern series and Habgood's (1985 Old World Late Pleistocene fossil hominids. The comparison between Lapa Vermelha IV Hominid 1 and Howells' series was based on canonical variate analysis, including 45 size-corrected craniometric variables, while the comparison with fossil hominids was based on principal component analysis, including 16 size-corrected variables. In the first case, Lapa Vermelha IV Hominid 1 exhibited an undisputed morphological affinity firstly with Africans and secondly with South Pacific populations. In the second comparison, the earliest known American skeleton had its closest similarities with early Australians, Zhoukoudian Upper Cave 103, and Taforalt 18. The results obtained clearly confirm the idea that the Americas were first colonized by a generalized Homo sapiens population which inhabited East Asia in the Late Pleistocene, before the definition of the classic Mongoloid morphology.

Higher spin currents in Wolf space. Part I

Energy Technology Data Exchange (ETDEWEB)

Ahn, Changhyun [Department of Physics, Kyungpook National University,Taegu 702-701 (Korea, Republic of)

2014-03-20

For the N=4 superconformal coset theory described by ((SU(N+2))/(SU(N))) (that contains a Wolf space) with N=3, the N=2 WZW affine current algebra with constraints is obtained. The 16 generators of the large N=4 linear superconformal algebra are described by those WZW affine currents explicitly. By factoring out four spin-(1/2) currents and the spin-1 current from these 16 generators, the remaining 11 generators (spin-2 current, four spin-(3/2) currents, and six spin-1 currents) corresponding to the large N=4 nonlinear superconformal algebra are obtained. Based on the recent work by Gaberdiel and Gopakumar on the large N=4 holography, the extra 16 currents, with spin contents (1,(3/2),(3/2),2), ((3/2),2,2,(5/2)), ((3/2),2,2,(5/2)), and (2,(5/2),(5/2),3) described in terms of N=2 multiplets, are obtained and realized by the WZW affine currents. As a first step towards N=4W algebra (which is NOT known so far), the operator product expansions (OPEs) between the above 11 currents and these extra 16 higher spin currents are found explicitly. It turns out that the composite fields with definite U(1) charges, made of above (11+16) currents (which commute with the Wolf space subgroup SU(N=3)×SU(2)×U(1) currents), occur in the right hand sides of these OPEs.

Plasma-polymerized films providing selective affinity to the polarity of vaporized organic solvents

International Nuclear Information System (INIS)

Akimoto, Takuo; Ikeshita, Yusuke; Terashima, Ryo; Karube, Isao

2009-01-01

Plasma-polymerized films (PPFs) were fabricated as recognition membranes for a vapor-sensing device, and their affinity to vaporized organic solvents was evaluated with surface plasmon resonance. The affinity we intended to create is the selective sorption of the vaporized organic solvents depending on their polarity. For this purpose, acetonitrile, ethylenediamine (EDA), styrene, hexamethyldisiloxane (HMDSO), and hexamethyldisilazane were used to fabricate PPFs. Vaporized methanol, ethanol, and 1-propanol were used as high-polar solvents to be analyzed. Hexane, toluene, and p-xylene were used as low-polar solvents. As a result, the HMDSO-PPF with 97.3 o of contact angle was found to provide affinity to the low-polar solvents. In contrast, the EDA-PPF with 7.1 o of contact angle provided affinity to the high-polar solvents. Observations of the surface morphology of the HMDSO- and EDA-PPFs with a scanning electron microscope revealed that they are composed of nano-scale islands.

Proadifen-sensitive high affinity binding of /sup 3/H-alaproclate to liver membranes

Energy Technology Data Exchange (ETDEWEB)

Ross, S.B.

1987-01-01

/sup 3/H-alaproclate, a selective 5/sub h/ydroxytryptamine uptake inhibitor, was found to bind to microsomal membranes from the rat liver with high affinity (K/sub D/-=3 nM) and large capacity (B/sub max/ about 2 nmol/g liver). This binding was stereoselective since S-( - )-alaproclate was 30 times more potent than the R-( + )-enantiomer to displace the /sup 3/H-labelled racemate. Proadifen (SKF 525A), an inhibitor of cytochrome P-450, displaced the /sup 3/H-alaproclate binding with the same, high affinity (K/sub i/=3 nM) as alaproclate itself. Repeated treatment with phenobarbital sodium (5x75 mg/kg intraperitoneally) increased the number of alaproclate binding sites 7-8 times without changing the affinity. However, most of the phenobarbital induced /sup 3/H-alaproclate binding was not displaceable by proadifen, showing the presence of at least two different high affinity binding sites. The possible involvement of cytochrome P-450 in the alaproclate binding is discussed.

Affinity for music in Wolf-Hirschhorn syndrome: two case reports.

Science.gov (United States)

Arakawa, Chikako; Fujita, Yukihiko; Fuchigami, Tatsuo; Kawamura, Yuki; Ishii, Wakako; Endo, Ayumi; Kohira, Ryutaro; Takahashi, Shori

2014-10-01

Wolf-Hirschhorn syndrome is a congenital malformation syndrome resulting from deletion of the short arm of chromosome 4. Individuals with Wolf-Hirschhorn syndrome may have a "Greek warrior helmet" appearance, growth retardation, developmental delay, muscular hypotonia, epilepsy, and difficulty with language including verbal communication. An affinity for music has not previously been reported in these patients. We describe two patients with Wolf-Hirschhorn syndrome who both have a strong affinity for music. One patient is a 20-year-old woman who likes to listen to music all day and can hum many tunes. The other patient is a 9-year-old girl who is calmed by music and received music therapy, with subsequent improvement in her communication skills (eye contact, joint attention, and vocalizations to request music). Individuals with Wolf-Hirschhorn syndrome may have a strong affinity for music and may benefit from music therapy. Additional studies are needed to investigate the interest in music in individuals with Wolf-Hirschhorn syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

Simulated electron affinity tuning in metal-insulator-metal (MIM) diodes

Science.gov (United States)

Mistry, Kissan; Yavuz, Mustafa; Musselman, Kevin P.

2017-05-01

Metal-insulator-metal diodes for rectification applications must exhibit high asymmetry, nonlinearity, and responsivity. Traditional methods of improving these figures of merit have consisted of increasing insulator thickness, adding multiple insulator layers, and utilizing a variety of metal contact combinations. However, these methods have come with the price of increasing the diode resistance and ultimately limiting the operating frequency to well below the terahertz regime. In this work, an Airy Function Transfer Matrix simulation method was used to observe the effect of tuning the electron affinity of the insulator as a technique to decrease the diode resistance. It was shown that a small increase in electron affinity can result in a resistance decrease in upwards of five orders of magnitude, corresponding to an increase in operating frequency on the same order. Electron affinity tuning has a minimal effect on the diode figures of merit, where asymmetry improves or remains unaffected and slight decreases in nonlinearity and responsivity are likely to be greatly outweighed by the improved operating frequency of the diode.

Recombinant spider silk genetically functionalized with affinity domains.

Science.gov (United States)

Jansson, Ronnie; Thatikonda, Naresh; Lindberg, Diana; Rising, Anna; Johansson, Jan; Nygren, Per-Åke; Hedhammar, My

2014-05-12

Functionalization of biocompatible materials for presentation of active protein domains is an area of growing interest. Herein, we describe a strategy for functionalization of recombinant spider silk via gene fusion to affinity domains of broad biotechnological use. Four affinity domains of different origin and structure; the IgG-binding domains Z and C2, the albumin-binding domain ABD, and the biotin-binding domain M4, were all successfully produced as soluble silk fusion proteins under nondenaturing purification conditions. Silk films and fibers produced from the fusion proteins were demonstrated to be chemically and thermally stable. Still, the bioactive domains are concluded to be folded and accessible, since their respective targets could be selectively captured from complex samples, including rabbit serum and human plasma. Interestingly, materials produced from mixtures of two different silk fusion proteins displayed combined binding properties, suggesting that tailor-made materials with desired stoichiometry and surface distributions of several binding domains can be produced. Further, use of the IgG binding ability as a general mean for presentation of desired biomolecules could be demonstrated for a human vascular endothelial growth factor (hVEGF) model system, via a first capture of anti-VEGF IgG to silk containing the Z-domain, followed by incubation with hVEGF. Taken together, this study demonstrates the potential of recombinant silk, genetically functionalized with affinity domains, for construction of biomaterials capable of presentation of almost any desired biomolecule.

The electron affinity of some radiotherapeutic agents used in cancer therapy

International Nuclear Information System (INIS)

Wold, E.; Kaalhus, O.; Johansen, E.S.; Ekse, A.T.

1980-01-01

In order to evaluate whether chemotherapeutic compounds applied in cancer treatment might interact with radiation as anoxic cell sensitizers, the electron-affinic properties of DTIC (5-(3,3-dimethyl-1-triazeno)imidazole-4 carboxamide) AIC 4(5)-aminoimidazole-5(4)-carboxamide, hydroxyurea, busulfan and cyclophosphamide were studied by pulse radiolysis. Reaction rates with hydrated electrons were determined for all these compounds. With the exception of DTIC, they all reacted much more slowly with electrons than do most electron-affinic sensitizers. One-electron reduction potentials were determined for DTIC, AIC and hydroxyurea. The values were all in the region for the onset of sensitization, with hydroxyurea as the most promising (E 7 1 = -0.552 V). For busulfan and cyclophosphamide no value could be determined, but these compounds are probably less electron-affinic than hydroxyurea. A possible application of chemotherapeutic agents as radiosensitizers is discussed. (author)

Single-cell measurement of red blood cell oxygen affinity.

Science.gov (United States)

Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M; Schonbrun, Ethan

2015-08-11

Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they 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 Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability.

Optimizing scoring function of protein-nucleic acid interactions with both affinity and specificity.

Directory of Open Access Journals (Sweden)

Zhiqiang Yan

Full Text Available Protein-nucleic acid (protein-DNA and protein-RNA recognition is fundamental to the regulation of gene expression. Determination of the structures of the protein-nucleic acid recognition and insight into their interactions at molecular level are vital to understanding the regulation function. Recently, quantitative computational approach has been becoming an alternative of experimental technique for predicting the structures and interactions of biomolecular recognition. However, the progress of protein-nucleic acid structure prediction, especially protein-RNA, is far behind that of the protein-ligand and protein-protein structure predictions due to the lack of reliable and accurate scoring function for quantifying the protein-nucleic acid interactions. In this work, we developed an accurate scoring function (named as SPA-PN, SPecificity and Affinity of the Protein-Nucleic acid interactions for protein-nucleic acid interactions by incorporating both the specificity and affinity into the optimization strategy. Specificity and affinity are two requirements of highly efficient and specific biomolecular recognition. Previous quantitative descriptions of the biomolecular interactions considered the affinity, but often ignored the specificity owing to the challenge of specificity quantification. We applied our concept of intrinsic specificity to connect the conventional specificity, which circumvents the challenge of specificity quantification. In addition to the affinity optimization, we incorporated the quantified intrinsic specificity into the optimization strategy of SPA-PN. The testing results and comparisons with other scoring functions validated that SPA-PN performs well on both the prediction of binding affinity and identification of native conformation. In terms of its performance, SPA-PN can be widely used to predict the protein-nucleic acid structures and quantify their interactions.

Identification of Affine Linear Parameter Varying Models for Adaptive Interventions in Fibromyalgia Treatment.

Science.gov (United States)

Dos Santos, P Lopes; Deshpande, Sunil; Rivera, Daniel E; Azevedo-Perdicoúlis, T-P; Ramos, J A; Younger, Jarred

2013-12-31

There is good evidence that naltrexone, an opioid antagonist, has a strong neuroprotective role and may be a potential drug for the treatment of fibromyalgia. In previous work, some of the authors used experimental clinical data to identify input-output linear time invariant models that were used to extract useful information about the effect of this drug on fibromyalgia symptoms. Additional factors such as anxiety, stress, mood, and headache, were considered as additive disturbances. However, it seems reasonable to think that these factors do not affect the drug actuation, but only the way in which a participant perceives how the drug actuates on herself. Under this hypothesis the linear time invariant models can be replaced by State-Space Affine Linear Parameter Varying models where the disturbances are seen as a scheduling signal signal only acting at the parameters of the output equation. In this paper a new algorithm for identifying such a model is proposed. This algorithm minimizes a quadratic criterion of the output error. Since the output error is a linear function of some parameters, the Affine Linear Parameter Varying system identification is formulated as a separable nonlinear least squares problem. Likewise other identification algorithms using gradient optimization methods several parameter derivatives are dynamical systems that must be simulated. In order to increase time efficiency a canonical parametrization that minimizes the number of systems to be simulated is chosen. The effectiveness of the algorithm is assessed in a case study where an Affine Parameter Varying Model is identified from the experimental data used in the previous study and compared with the time-invariant model.

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

Energy Technology Data Exchange (ETDEWEB)

Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Moran, Jeffery H. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Arkansas Department of Public Health, Public Health Laboratory, Little Rock, AR 72205 (United States); Prather, Paul L., E-mail: pratherpaull@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

2013-06-01

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB{sub 1}Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB{sub 2}Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB{sub 2}Rs (hCB{sub 2}Rs). The affinity of cannabinoids for hCB{sub 2}Rs was determined by competition binding studies employing CHO-hCB{sub 2} membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB{sub 2} cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB{sub 2}Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB{sub 2}Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB{sub 2}R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB{sub 2}Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB{sub 2}Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB{sub 1} and CB{sub 2}Rs. - Highlights: • JWH-018

Molecular basis of a high affinity murine interleukin-5 receptor.

OpenAIRE

Devos, R; Plaetinck, G; Van der Heyden, J; Cornelis, S; Vandekerckhove, J; Fiers, W; Tavernier, J

1991-01-01

The mouse interleukin-5 receptor (mIL-5R) consists of two components one of which, the mIL-5R alpha-chain, binds mIL-5 with low affinity. Recently we demonstrated that monoclonal antibodies (Mabs) recognizing the second mIL-5R beta-chain, immunoprecipitate a p130-140 protein doublet which corresponds to the mIL-3R and the mIL-3R-like protein, the latter chain for which so far no ligand has been identified. In this study we show that a high affinity mIL-5R can be reconstituted on COS1 cells by...

Identification of high- and low-affinity NGF receptors during development of the chicken central nervous system

International Nuclear Information System (INIS)

Escandon, E.; Chao, M.V.

1990-01-01

In order to study regulation of the nerve growth factor (NGF) receptor during embryogenesis in chick brain, we have used affinity crosslinking of tissues with 125 I-NGF. NGF interacts with high- and low-affinity receptors; high-affinity receptors are required for the majority of NGF's actions. Most measurements of receptor levels do not distinguish between high- and low-affinity forms of the receptor. We have used the lipophilic crosslinking agent HSAB to identify the high-affinity, functional receptor during development of the chicken central nervous system. A peak of expression during Embryonic Days 5-10 was detected in all regions of the chicken central nervous system, but, shortly after birth, only the cerebellar region displays significant levels of NGF receptor protein. The time course of expression confirms the dramatic regulation of the NGF receptor gene during defined embryonic periods. The detection of high-affinity NGF receptors in brain and neural retina provides strong evidence that NGF is involved in essential ontogenetic events in the development of the chicken central nervous system

Enhanced binding by dextran-grafting to Protein A affinity chromatographic media.

Science.gov (United States)

Zhao, Lan; Zhu, Kai; Huang, Yongdong; Li, Qiang; Li, Xiunan; Zhang, Rongyue; Su, Zhiguo; Wang, Qibao; Ma, Guanghui

2017-04-01

Dextran-grafted Protein A affinity chromatographic medium was prepared by grafting dextran to agarose-based matrix, followed by epoxy-activation and Protein A coupling site-directed to sulfhydryl groups of cysteine molecules. An enhancement of both the binding performance and the stability was achieved for this dextran-grafted Protein A chromatographic medium. Its dynamic binding capacity was 61 mg immunoglobulin G/mL suction-dried gel, increased by 24% compared with that of the non-grafted medium. The binding capacity of dextran-grafted medium decreased about 7% after 40 cleaning-in-place cycles, much lower than that of the non-grafted medium as decreased about 15%. Confocal laser scanning microscopy results showed that immunoglobulin G was bound to both the outside and the inside of dextran-grafted medium faster than that of non-grafted one. Atomic force microscopy showed that this dextran-grafted Protein A medium had much rougher surface with a vertical coordinate range of ±80 nm, while that of non-grafted one was ±10 nm. Grafted dextran provided a more stereo surface morphology and immunoglobulin G molecules were more easily to be bound. This high-performance dextran-grafted Protein A affinity chromatographic medium has promising applications in large-scale antibody purification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characteristics of high affinity and low affinity adenosine binding sites in human cerebral cortex

International Nuclear Information System (INIS)

John, D.; Fox, I.V.

1986-01-01

The binding characteristics of human brain cortical membrane fractions were evaluated to test the hypothesis that there are A 1 and A 2 adenosine binding sites. The ligands used were 2-chloro(8- 3 H) adenosine and N 6 -(adenine-2, 8- 3 H) cyclohexayladenosine. Binding of chloroadenosine to human brain cortical membranes was time dependent, reversible and concentration dependent. The kinetic constant determinations from binding studies of the adenosine receptor are presented. Utilizing tritium-cyclohexyladenosine as ligand the authors observed evidence for a high affinity binding site in human brain cortical membranes with a kd of 5 nM

Transformations Based on Continuous Piecewise-Affine Velocity Fields

DEFF Research Database (Denmark)

Freifeld, Oren; Hauberg, Søren; Batmanghelich, Kayhan

2017-01-01

We propose novel finite-dimensional spaces of well-behaved transformations. The latter are obtained by (fast and highly-accurate) integration of continuous piecewise-affine velocity fields. The proposed method is simple yet highly expressive, effortlessly handles optional constraints (e.g., volum...

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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Accurate determination of the oxidative phosphorylation affinity for ADP in isolated mitochondria.

Directory of Open Access Journals (Sweden)

Gilles Gouspillou

Full Text Available BACKGROUND: Mitochondrial dysfunctions appear strongly implicated in a wide range of pathologies. Therefore, there is a growing need in the determination of the normal and pathological integrated response of oxidative phosphorylation to cellular ATP demand. The present study intends to address this issue by providing a method to investigate mitochondrial oxidative phosphorylation affinity for ADP in isolated mitochondria. METHODOLOGY/PRINCIPAL FINDINGS: The proposed method is based on the simultaneous monitoring of substrate oxidation (determined polarographically and phosphorylation (determined using the glucose-hexokinase glucose-6-phosphate dehydrogenase-NADP(+ enzymatic system rates, coupled to the determination of actual ADP and ATP concentrations by bioluminescent assay. This enzymatic system allows the study of oxidative phosphorylation during true steady states in a wide range of ADP concentrations. We demonstrate how the application of this method allows an accurate determination of mitochondrial affinity for ADP from both oxidation (K(mVox and phosphorylation (K(mVp rates. We also demonstrate that determination of K(mVox leads to an important overestimation of the mitochondrial affinity for ADP, indicating that mitochondrial affinity for ADP should be determined using phosphorylation rate. Finally, we show how this method allows the direct and precise determination of the mitochondrial coupling efficiency. Data obtained from rat skeletal muscle and liver mitochondria illustrate the discriminating capabilities of this method. CONCLUSIONS/SIGNIFICANCE: Because the proposed method allows the accurate determination of mitochondrial oxidative phosphorylation affinity for ADP in isolated mitochondria, it also opens the route to a better understanding of functional consequences of mitochondrial adaptations/dysfunctions arising in various physiological/pathophysiological conditions.

Structural basis for high substrate-binding affinity and enantioselectivity of 3-quinuclidinone reductase AtQR

International Nuclear Information System (INIS)

Hou, Feng; Miyakawa, Takuya; Kataoka, Michihiko; Takeshita, Daijiro; Kumashiro, Shoko; Uzura, Atsuko; Urano, Nobuyuki; Nagata, Koji; Shimizu, Sakayu; Tanokura, Masaru

2014-01-01

Highlights: • Crystal structure of AtQR has been determined at 1.72 Å. • NADH binding induces the formation of substrate binding site. • AtQR possesses a conserved hydrophobic wall for stereospecific binding of substrate. • Additional Glu197 residue is critical to the high binding affinity. - Abstract: (R)-3-Quinuclidinol, a useful compound for the synthesis of various pharmaceuticals, can be enantioselectively produced from 3-quinuclidinone by 3-quinuclidinone reductase. Recently, a novel NADH-dependent 3-quinuclidionone reductase (AtQR) was isolated from Agrobacterium tumefaciens, and showed much higher substrate-binding affinity (>100 fold) than the reported 3-quinuclidionone reductase (RrQR) from Rhodotorula rubra. Here, we report the crystal structure of AtQR at 1.72 Å. Three NADH-bound protomers and one NADH-free protomer form a tetrameric structure in an asymmetric unit of crystals. NADH not only acts as a proton donor, but also contributes to the stability of the α7 helix. This helix is a unique and functionally significant part of AtQR and is related to form a deep catalytic cavity. AtQR has all three catalytic residues of the short-chain dehydrogenases/reductases family and the hydrophobic wall for the enantioselective reduction of 3-quinuclidinone as well as RrQR. An additional residue on the α7 helix, Glu197, exists near the active site of AtQR. This acidic residue is considered to form a direct interaction with the amine part of 3-quinuclidinone, which contributes to substrate orientation and enhancement of substrate-binding affinity. Mutational analyses also support that Glu197 is an indispensable residue for the activity

Structural basis for high substrate-binding affinity and enantioselectivity of 3-quinuclidinone reductase AtQR

Energy Technology Data Exchange (ETDEWEB)

Hou, Feng; Miyakawa, Takuya [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Kataoka, Michihiko [Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 559-8531 (Japan); Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Takeshita, Daijiro [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Kumashiro, Shoko [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Uzura, Atsuko [Research and Development Center, Nagase and Co., Ltd., 2-2-3 Muratani, Nishi-ku, Kobe 651-2241 (Japan); Urano, Nobuyuki [Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 559-8531 (Japan); Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Nagata, Koji [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Shimizu, Sakayu [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Faculty of Bioenvironmental Science, Kyoto Gakuen University, Sogabe-cho, Kameoka 621-8555 (Japan); Tanokura, Masaru, E-mail: amtanok@mail.ecc.u-tokyo.ac.jp [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan)

2014-04-18

Highlights: • Crystal structure of AtQR has been determined at 1.72 Å. • NADH binding induces the formation of substrate binding site. • AtQR possesses a conserved hydrophobic wall for stereospecific binding of substrate. • Additional Glu197 residue is critical to the high binding affinity. - Abstract: (R)-3-Quinuclidinol, a useful compound for the synthesis of various pharmaceuticals, can be enantioselectively produced from 3-quinuclidinone by 3-quinuclidinone reductase. Recently, a novel NADH-dependent 3-quinuclidionone reductase (AtQR) was isolated from Agrobacterium tumefaciens, and showed much higher substrate-binding affinity (>100 fold) than the reported 3-quinuclidionone reductase (RrQR) from Rhodotorula rubra. Here, we report the crystal structure of AtQR at 1.72 Å. Three NADH-bound protomers and one NADH-free protomer form a tetrameric structure in an asymmetric unit of crystals. NADH not only acts as a proton donor, but also contributes to the stability of the α7 helix. This helix is a unique and functionally significant part of AtQR and is related to form a deep catalytic cavity. AtQR has all three catalytic residues of the short-chain dehydrogenases/reductases family and the hydrophobic wall for the enantioselective reduction of 3-quinuclidinone as well as RrQR. An additional residue on the α7 helix, Glu197, exists near the active site of AtQR. This acidic residue is considered to form a direct interaction with the amine part of 3-quinuclidinone, which contributes to substrate orientation and enhancement of substrate-binding affinity. Mutational analyses also support that Glu197 is an indispensable residue for the activity.

Sequence2Vec: A novel embedding approach for modeling transcription factor binding affinity landscape

KAUST Repository

Dai, Hanjun

2017-07-26

Motivation: An accurate characterization of transcription factor (TF)-DNA affinity landscape is crucial to a quantitative understanding of the molecular mechanisms underpinning endogenous gene regulation. While recent advances in biotechnology have brought the opportunity for building binding affinity prediction methods, the accurate characterization of TF-DNA binding affinity landscape still remains a challenging problem. Results: Here we propose a novel sequence embedding approach for modeling the transcription factor binding affinity landscape. Our method represents DNA binding sequences as a hidden Markov model (HMM) which captures both position specific information and long-range dependency in the sequence. A cornerstone of our method is a novel message passing-like embedding algorithm, called Sequence2Vec, which maps these HMMs into a common nonlinear feature space and uses these embedded features to build a predictive model. Our method is a novel combination of the strength of probabilistic graphical models, feature space embedding and deep learning. We conducted comprehensive experiments on over 90 large-scale TF-DNA data sets which were measured by different high-throughput experimental technologies. Sequence2Vec outperforms alternative machine learning methods as well as the state-of-the-art binding affinity prediction methods.

Mechanisms of anaphylaxis in human low-affinity IgG receptor locus knock-in mice.

Science.gov (United States)

Gillis, Caitlin M; Jönsson, Friederike; Mancardi, David A; Tu, Naxin; Beutier, Héloïse; Van Rooijen, Nico; Macdonald, Lynn E; Murphy, Andrew J; Bruhns, Pierre

2017-04-01

Anaphylaxis can proceed through distinct IgE- or IgG-dependent pathways, which have been investigated in various mouse models. We developed a novel mouse strain in which the human low-affinity IgG receptor locus, comprising both activating (hFcγRIIA, hFcγRIIIA, and hFcγRIIIB) and inhibitory (hFcγRIIB) hFcγR genes, has been inserted into the equivalent murine locus, corresponding to a locus swap. We sought to determine the capabilities of hFcγRs to induce systemic anaphylaxis and identify the cell types and mediators involved. hFcγR expression on mouse and human cells was compared to validate the model. Passive systemic anaphylaxis was induced by injection of heat-aggregated human intravenous immunoglobulin and active systemic anaphylaxis after immunization and challenge. Anaphylaxis severity was evaluated based on hypothermia and mortality. The contribution of receptors, mediators, or cell types was assessed based on receptor blockade or depletion. The human-to-mouse low-affinity FcγR locus swap engendered hFcγRIIA/IIB/IIIA/IIIB expression in mice comparable with that seen in human subjects. Knock-in mice were susceptible to passive and active anaphylaxis, accompanied by downregulation of both activating and inhibitory hFcγR expression on specific myeloid cells. The contribution of hFcγRIIA was predominant. Depletion of neutrophils protected against hypothermia and mortality. Basophils contributed to a lesser extent. Anaphylaxis was inhibited by platelet-activating factor receptor or histamine receptor 1 blockade. Low-affinity FcγR locus-switched mice represent an unprecedented model of cognate hFcγR expression. Importantly, IgG-related anaphylaxis proceeds within a native context of activating and inhibitory hFcγRs, indicating that, despite robust hFcγRIIB expression, activating signals can dominate to initiate a severe anaphylactic reaction. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights

Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration.

Science.gov (United States)

Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E

2010-08-15

Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.

Evaluation of SDS depletion using an affinity spin column and IMS-MS detection

Energy Technology Data Exchange (ETDEWEB)

Hengel, Shawna M.; Floyd, Erica A.; Baker, Erin Shammel; Zhao, Rui; Wu, Si; Pasa-Tolic, Ljiljana

2012-11-01

While the use of detergents is necessary for a variety of protein isolation preparation protocols, often prior to mass spectral (MS) analysis, they are not compatible with MS analysis due to ion suppression and adduct formation. This manuscript describes optimization of detergent removal, using commercially available SDS depletion spin columns containing an affinity resin, providing for both increased protein recovery and thorough SDS removal. Ion mobility spectrometry coupled with mass spectrometry (IMS-MS) allowed for a concurrent analysis of both analyte and detergent. In the case of both proteins and peptides, higher detergent concentrations than previously reported provided an increase of sample recovery; however there was a limit as SDS was detected by IMS-MS at higher levels of SDS indicating incomplete detergent depletion. The results also suggest optimal conditions for SDS removal are dependent on the sample concentration. Overall, this study provides a useful guide for proteomic studies where SDS is required for efficient sample preparation.

Affinity maturation of a portable Fab–RNA module for chaperone-assisted RNA crystallography

Science.gov (United States)

Koirala, Deepak; Shelke, Sandip A; Dupont, Marcel; Ruiz, Stormy; DasGupta, Saurja; Bailey, Lucas J; Benner, Steven A; Piccirilli, Joseph A

2018-01-01

Abstract Antibody fragments such as Fabs possess properties that can enhance protein and RNA crystallization and therefore can facilitate macromolecular structure determination. In particular, Fab BL3–6 binds to an AAACA RNA pentaloop closed by a GC pair with ∼100 nM affinity. The Fab and hairpin have served as a portable module for RNA crystallization. The potential for general application make it desirable to adjust the properties of this crystallization module in a manner that facilitates its use for RNA structure determination, such as ease of purification, surface entropy or binding affinity. In this work, we used both in vitro RNA selection and phage display selection to alter the epitope and paratope sides of the binding interface, respectively, for improved binding affinity. We identified a 5′-GNGACCC-3′ consensus motif in the RNA and S97N mutation in complimentarity determining region L3 of the Fab that independently impart about an order of magnitude improvement in affinity, resulting from new hydrogen bonding interactions. Using a model RNA, these modifications facilitated crystallization under a wider range of conditions and improved diffraction. The improved features of the Fab–RNA module may facilitate its use as an affinity tag for RNA purification and imaging and as a chaperone for RNA crystallography. PMID:29309709

Substituting random forest for multiple linear regression improves binding affinity prediction of scoring functions: Cyscore as a case study.

Science.gov (United States)

Li, Hongjian; Leung, Kwong-Sak; Wong, Man-Hon; Ballester, Pedro J

2014-08-27

State-of-the-art protein-ligand docking methods are generally limited by the traditionally low accuracy of their scoring functions, which are used to predict binding affinity and thus vital for discriminating between active and inactive compounds. Despite intensive research over the years, classical scoring functions have reached a plateau in their predictive performance. These assume a predetermined additive functional form for some sophisticated numerical features, and use standard multivariate linear regression (MLR) on experimental data to derive the coefficients. In this study we show that such a simple functional form is detrimental for the prediction performance of a scoring function, and replacing linear regression by machine learning techniques like random forest (RF) can improve prediction performance. We investigate the conditions of applying RF under various contexts and find that given sufficient training samples RF manages to comprehensively capture the non-linearity between structural features and measured binding affinities. Incorporating more structural features and training with more samples can both boost RF performance. In addition, we analyze the importance of structural features to binding affinity prediction using the RF variable importance tool. Lastly, we use Cyscore, a top performing empirical scoring function, as a baseline for comparison study. Machine-learning scoring functions are fundamentally different from classical scoring functions because the former circumvents the fixed functional form relating structural features with binding affinities. RF, but not MLR, can effectively exploit more structural features and more training samples, leading to higher prediction performance. The future availability of more X-ray crystal structures will further widen the performance gap between RF-based and MLR-based scoring functions. This further stresses the importance of substituting RF for MLR in scoring function development.

From affine Hecke algebras to boundary symmetries

International Nuclear Information System (INIS)

Doikou, Anastasia

2005-01-01

Motivated by earlier works we employ appropriate realizations of the affine Hecke algebra and we recover previously known non-diagonal solutions of the reflection equation for the U q (gl n -bar ) case. The corresponding N site spin chain with open boundary conditions is then constructed and boundary non-local charges associated to the non-diagonal solutions of the reflection equation are derived, as coproduct realizations of the reflection algebra. With the help of linear intertwining relations involving the aforementioned solutions of the reflection equation, the symmetry of the open spin chain with the corresponding boundary conditions is exhibited, being essentially a remnant of the U q (gl n -bar ) algebra. More specifically, we show that representations of certain boundary non-local charges commute with the generators of the affine Hecke algebra and with the local Hamiltonian of the open spin chain for a particular choice of boundary conditions. Furthermore, we are able to show that the transfer matrix of the open spin chain commutes with a certain number of boundary non-local charges, depending on the choice of boundary conditions

Rapid Diagnostic Assay for Intact Influenza Virus Using a High Affinity Hemagglutinin Binding Protein.

Science.gov (United States)

Anderson, Caitlin E; Holstein, Carly A; Strauch, Eva-Maria; Bennett, Steven; Chevalier, Aaron; Nelson, Jorgen; Fu, Elain; Baker, David; Yager, Paul

2017-06-20

Influenza is a ubiquitous and recurring infection that results in approximately 500 000 deaths globally each year. Commercially available rapid diagnostic tests are based upon detection of the influenza nucleoprotein, which are limited in that they are unable to differentiate by species and require an additional viral lysis step. Sample preprocessing can be minimized or eliminated by targeting the intact influenza virus, thereby reducing assay complexity and leveraging the large number of hemagglutinin proteins on the surface of each virus. Here, we report the development of a paper-based influenza assay that targets the hemagglutinin protein; the assay employs a combination of antibodies and novel computationally designed, recombinant affinity proteins as the capture and detection agents. This system leverages the customizability of recombinant protein design to target the conserved receptor-binding pocket of the hemagglutinin protein and to match the trimeric nature of hemagglutinin for improved avidity. Using this assay, we demonstrate the first instance of intact influenza virus detection using a combination of antibody and affinity proteins within a porous network. The recombinant head region binder based assays yield superior analytical sensitivity as compared to the antibody based assay, with lower limits of detection of 3.54 × 10 7 and 1.34 × 10 7 CEID 50 /mL for the mixed and all binder stacks, respectively. Not only does this work describe the development of a novel influenza assay, it also demonstrates the power of recombinant affinity proteins for use in rapid diagnostic assays.

Evaluation of monoclonal anti-A and anti-B and affinity-purified Ulex europaeus lectin I for forensic blood grouping.

Science.gov (United States)

Gaensslen, R E; Lee, H C; Carroll, J E

1984-01-01

Two different monoclonal anti-A and anti-B and several different affinity purified Ulex europaeus lectin I reagents were evaluated and compared with conventional anti-A and anti-B sera and Ulex anti-H for serologic properties, in inhibition tests with secretor salivas, and in elution tests with bloodstains. The monoclonal and purified reagents were found to be comparable to conventional ones, and accordingly suitable for forensic inhibition and elution procedures.

[3H]-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor

International Nuclear Information System (INIS)

Branchek, T.; Adham, N.; Macchi, M.; Kao, H.T.; Hartig, P.R.

1990-01-01

The binding properties of the 5-hydroxytryptamine2 (5-HT2) receptor have been the subject of much interest and debate in recent years. The hallucinogenic amphetamine derivative 4-bromo-2,5-dimethoxyphenylisopropylamine (DOB) has been shown to bind to a small number of binding sites with properties very similar to [3H]ketanserin-labeled 5-HT2 receptors, but with much higher agonist affinities. Some researchers have interpreted this as evidence for the existence of a new subtype of 5-HT2 receptor (termed 5-HT2A), whereas others have interpreted these data as indicative of agonist high affinity and agonist low affinity states for the 5-HT2 receptor. In this investigation, a cDNA clone encoding the serotonin 5-HT2 receptor was transiently transfected into monkey kidney Cos-7 cells and stably transfected into mouse fibroblast L-M(TK-) cells. In both systems, expression of this single serotonin receptor cDNA led to the appearance of both [3H]DOB and [3H]ketanserin binding sites with properties that matched their binding characteristics in mammalian brain homogenates. Addition of guanosine 5'-(beta, gamma-imido) triphosphate [Gpp(NH)p] to this system caused a rightward shift and steepening of agonist competition curves for [3H] ketanserin binding, converting a two-site binding curve to a single low affinity binding state. Gpp(NH)p addition also caused a 50% decrease in the number of high affinity [3H]DOB binding sites, with no change in the dissociation constant of the remaining high affinity states. These data on a single human 5-HT2 receptor cDNA expressed in two different transfection host cells indicate that [3H]DOB and [3H]ketanserin binding reside on the same gene product, apparently interacting with agonist and antagonist conformations of a single human 5-HT2 receptor protein

[Affine transformation-based automatic registration for peripheral digital subtraction angiography (DSA)].

Science.gov (United States)

Kong, Gang; Dai, Dao-Qing; Zou, Lu-Min

2008-07-01

In order to remove the artifacts of peripheral digital subtraction angiography (DSA), an affine transformation-based automatic image registration algorithm is introduced here. The whole process is described as follows: First, rectangle feature templates are constructed with their centers of the extracted Harris corners in the mask, and motion vectors of the central feature points are estimated using template matching technology with the similarity measure of maximum histogram energy. And then the optimal parameters of the affine transformation are calculated with the matrix singular value decomposition (SVD) method. Finally, bilinear intensity interpolation is taken to the mask according to the specific affine transformation. More than 30 peripheral DSA registrations are performed with the presented algorithm, and as the result, moving artifacts of the images are removed with sub-pixel precision, and the time consumption is less enough to satisfy the clinical requirements. Experimental results show the efficiency and robustness of the algorithm.

Generalized magnification in visual optics. Part 2: Magnification as affine transformation

Directory of Open Access Journals (Sweden)

W. F. Harris

2010-12-01

Full Text Available In astigmatic systems magnification may be different in different directions.  It may also be accompanied by rotation or reflection.  These changes from object to image are examples of generalized magnification.  They are represented by  2 2×  matrices.  Because they are linear transformations they can be called linear magnifications.  Linear magnifications account for a change in appearance without regard to position.  Mathematical structure suggests a natural further generalization to a magnification that is complete in the sense that it accountsfor change in appearance and position.  It is represented by a  3 3×  matrix with a dummy third row. The transformation is called affine in linear algebra which suggests that these generalized magnifica-tions be called affine magnifications.  The purpose of the paper is to define affine magnification in the context of astigmatic optics.  Several examples are presented and illustrated graphically. (S Afr Optom 2010 69(4 166-172

Unambiguous formalism for higher order Lagrangian field theories

International Nuclear Information System (INIS)

Campos, Cedric M; De Leon, Manuel; De Diego, David MartIn; Vankerschaver, Joris

2009-01-01

The aim of this paper is to propose an unambiguous intrinsic formalism for higher order field theories which avoids the arbitrariness in the generalization of the conventional description of field theories, and implies the existence of different Cartan forms and Legendre transformations. We propose a differential-geometric setting for the dynamics of a higher order field theory, based on the Skinner and Rusk formalism for mechanics. This approach incorporates aspects of both the Lagrangian and the Hamiltonian description, since the field equations are formulated using the Lagrangian on a higher order jet bundle and the canonical multisymplectic form on its affine dual. As both of these objects are uniquely defined, the Skinner-Rusk approach has the advantage that it does not suffer from the arbitrariness in conventional descriptions. The result is that we obtain a unique and global intrinsic version of the Euler-Lagrange equations for higher order field theories. Several examples illustrate our construction.

General super Virasoro construction on affine G

International Nuclear Information System (INIS)

Mohammedi, N.

1990-10-01

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

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…

Peptide receptor radionuclide therapy (PRRT) using Lu-177 DOTA-NOC and Lu-177 DOTA-TATE: Comparative results

International Nuclear Information System (INIS)

Wehrmann, C.; Senftleben, S.; Baum, R.P.

2007-01-01

Full text: Aim: One of the few treatment options for inoperable neuroendocrine tumors (NET) is peptide receptor radiotherapy with somatostatin analogues. DOTA-NOC shows the highest affinity to the somatostatin receptors (sstr) 3 and 5 and a very high affinity to sstr 2. We compared the dosimetric parameters uptake, half-life (kinetics) and mean absorbed organ and tumor doses of 177 Lu DOTANOC and 177 Lu DOTA-TATE. Methods: 139 patients with neuroendocrine tumors with high sstr expression (verified by Ga-68 DOTA-NOC PET/CT) were studied. 130 patients (57m, 73f; aged 60±11a) were treated with 2.5-7.4 GBq Lu-177 DOTA-TATE and 9 patients (3m, 6f, aged 64±10a) with 3.6-7.4 GBq Lu-177 DOTA-NOC. Whole-body scans were performed after 0.5h, 3h, 24h, 48h, 72h and 96h p.i. Blood samples from 23 patients were obtained after therapy. By means of geometric mean and after background correction, ROI results were used to calculate the estimated absorbed organ and tumor doses according to the MIRD-scheme (OLINDA software). Results: Lu-177 DOTA-NOC showed a higher uptake as compared to Lu-177 DOTATATE (=100%): for whole-body about 38% and in normal tissue 36%, in the spleen 17% and in the kidneys 18%. The tumor uptake was about 5% higher for DOTA-TATE. The effective half-life for whole-body was comparable for both peptides (t1/2a NOC 2.9h vs. TATE 2.4h and t1/2b NOC 54h vs. TATE 56h). In normal tissue, t1/2a was similar (NOC 3.3h; TATE 2.6h) but the t1/2b was longer for DOTA-TATE (NOC 43h; TATE 48h). t1/2b was longer for DOTA-NOC in the spleen (NOC 81h; TATE 72h) and in the kidney (NOC 68.1h; TATE 65h). The mean absorbed dose in the kidney (TATE 5Sv; NOC 6Sv) and spleen (TATE 7Sv; NOC 8Sv) was higher for DOTA-NOC. In the tumor, the t1/2b was higher for DOTA-TATE (NOC 65h; TATE 77h). For DOTA-TATE the whole-body dose was lower (0.27Sv) as compared to DOTA-NOC (0.38 Sv) (significant by unpaired sign test). The estimated mean absorbed tumor doses were 47+/-66 Sv for DOTA-TATE and 35

Pathways to an East Asian Higher Education Area: A Comparative Analysis of East Asian and European Regionalization Processes

Science.gov (United States)

Chao, Roger Y., Jr.

2014-01-01

The Author argues that historical regional developments in Europe and East Asia greatly influence the formation of an East Asian Higher Education Area. As such, this article compares European and East Asian regionalization and higher education regionalization processes to show this path dependency in East Asian regionalization of higher education…

Solitons, τ-functions and hamiltonian reduction for non-Abelian conformal affine Toda theories

Science.gov (United States)

Ferreira, L. A.; Miramontes, J. Luis; Guillén, Joaquín Sánchez

1995-02-01

We consider the Hamiltonian reduction of the "two-loop" Wess-Zumino-Novikov-Witten model (WZNW) based on an untwisted affine Kac-Moody algebra G. The resulting reduced models, called Generalized Non-Abelian Conformal Affine Toda (G-CAT), are conformally invariant and a wide class of them possesses soliton solutions; these models constitute non-Abelian generalizations of the conformal affine Toda models. Their general solution is constructed by the Leznov-Saveliev method. Moreover, the dressing transformations leading to the solutions in the orbit of the vacuum are considered in detail, as well as the τ-functions, which are defined for any integrable highest weight representation of G, irrespectively of its particular realization. When the conformal symmetry is spontaneously broken, the G-CAT model becomes a generalized affine Toda model, whose soliton solutions are constructed. Their masses are obtained exploring the spontaneous breakdown of the conformal symmetry, and their relation to the fundamental particle masses is discussed. We also introduce what we call the two-loop Virasoro algebra, describing extended symmetries of the two-loop WZNW models.

Affinity labeling of the folate-methotrexate transporter from Leishmania donovani

International Nuclear Information System (INIS)

Beck, J.T.; Ullman, B.

1989-01-01

An affinity labeling technique has been developed to identify the folate-methotrexate transporter of Leishmania donovani promastigotes using activated derivatives of the ligands. These activated derivatives were synthesized by incubating folate and methotrexate with a 10-fold excess of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) for 10 min at ambient temperature in dimethyl sulfoxide. When intact wild-type (DI700) Leishmania donovani or preparations of their membranes were incubated with a 0.4 μM concentration of either activated [ 3 H]folate or activated [ 3 H]methotrexate, the radiolabeled ligands were covalently incorporated into a polypeptide with a molecular weight of approximately 46,000, as demonstrated by SDS-polyacrylamide gel electrophoresis. No affinity labeling of a 46,000-dalton protein was observed when equimolar concentrations of activated radiolabeled ligands were incubated with intact cells or membranes prepared from a methotrexate-resistant mutant clone of Leishmania donovani, MTXA5, that is genetically defective in folate-methotrexate transport capability. Time course studies indicated that maximal labeling of the 46,000-dalton protein occurred within 5-10 min of incubation of intact cells with activated ligand. These studies provide biochemical evidence that the folate-methotrexate transporter of Leishmania donovani can be identified in crude extracts by an affinity labeling technique and serve as a prerequisite to further analysis of the transport protein by providing a vehicle for subsequent purification of this membrane carrier. Moreover, these investigations suggest that the affinity labeling technique using EDC-activated ligands may be exploitable to analyze other cell surface binding proteins in Leishmania donovani, as well as in other organisms

A comparative study of Dirac quasinormal modes of charged black holes in higher dimensions

International Nuclear Information System (INIS)

Chakrabarti, Sayan K.

2009-01-01

In this work we study the Dirac quasinormal modes of higher dimensional charged black holes. Higher dimensional Reissner-Nordstroem type black holes as well as charged black holes in Einstein-Gauss-Bonnet theories are studied for fermionic perturbations using WKB method. A comparative study of the quasinormal modes in the two different theories of gravity has been performed. The behavior of the frequencies with the variation of black hole parameters as well as with the variation of space-time dimensions is studied. We also study the large multipole number limit of the black hole potential in order to look for an analytic expression for the frequencies. (orig.)

Effect of Polysorbate 20 and Polysorbate 80 on the Higher-Order Structure of a Monoclonal Antibody and Its Fab and Fc Fragments Probed Using 2D Nuclear Magnetic Resonance Spectroscopy.

Science.gov (United States)

Singh, Surinder M; Bandi, Swati; Jones, David N M; Mallela, Krishna M G

2017-12-01

We examined how polysorbate 20 (PS20; Tween 20) and polysorbate 80 (PS80; Tween 80) affect the higher-order structure of a monoclonal antibody (mAb) and its antigen-binding (Fab) and crystallizable (Fc) fragments, using near-UV circular dichroism and 2D nuclear magnetic resonance (NMR). Both polysorbates bind to the mAb with submillimolar affinity. Binding causes significant changes in the tertiary structure of mAb with no changes in its secondary structure. 2D 13 C- 1 H methyl NMR indicates that with increasing concentration of polysorbates, the Fab region showed a decrease in crosspeak volumes. In addition to volume changes, PS20 caused significant changes in the chemical shifts compared to no changes in the case of PS80. No such changes in crosspeak volumes or chemical shifts were observed in the case of Fc region, indicating that polysorbates predominantly affect the Fab region compared to the Fc region. This differential effect of polysorbates on the Fab and Fc regions was because of the lesser thermodynamic stability of the Fab compared to the Fc. These results further indicate that PS80 is the preferred polysorbate for this mAb formulation, because it offers higher protection against aggregation, causes lesser structural perturbation, and has weaker binding affinity with fewer binding sites compared to PS20. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Comparing Multi-Step IMAC and Multi-Step TiO2 Methods for Phosphopeptide Enrichment

Science.gov (United States)

Yue, Xiaoshan; Schunter, Alissa; Hummon, Amanda B.

2016-01-01

Phosphopeptide enrichment from complicated peptide mixtures is an essential step for mass spectrometry-based phosphoproteomic studies to reduce sample complexity and ionization suppression effects. Typical methods for enriching phosphopeptides include immobilized metal affinity chromatography (IMAC) or titanium dioxide (TiO2) beads, which have selective affinity and can interact with phosphopeptides. In this study, the IMAC enrichment method was compared with the TiO2 enrichment method, using a multi-step enrichment strategy from whole cell lysate, to evaluate their abilities to enrich for different types of phosphopeptides. The peptide-to-beads ratios were optimized for both IMAC and TiO2 beads. Both IMAC and TiO2 enrichments were performed for three rounds to enable the maximum extraction of phosphopeptides from the whole cell lysates. The phosphopeptides that are unique to IMAC enrichment, unique to TiO2 enrichment, and identified with both IMAC and TiO2 enrichment were analyzed for their characteristics. Both IMAC and TiO2 enriched similar amounts of phosphopeptides with comparable enrichment efficiency. However, phosphopeptides that are unique to IMAC enrichment showed a higher percentage of multi-phosphopeptides, as well as a higher percentage of longer, basic, and hydrophilic phosphopeptides. Also, the IMAC and TiO2 procedures clearly enriched phosphopeptides with different motifs. Finally, further enriching with two rounds of TiO2 from the supernatant after IMAC enrichment, or further enriching with two rounds of IMAC from the supernatant TiO2 enrichment does not fully recover the phosphopeptides that are not identified with the corresponding multi-step enrichment. PMID:26237447

Reconstitution of high-affinity opioid agonist binding in brain membranes

Energy Technology Data Exchange (ETDEWEB)

Remmers, A.E.; Medzihradsky, F. (Univ. of Michigan Medical School, Ann Arbor (United States))

1991-03-15

In synaptosomal membranes from rat brain cortex, the {mu} selective agonist ({sup 3}H)dihydromorphine in the absence of sodium, and the nonselective antagonist ({sup 3}H)naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with K{sub d} values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 {mu}M guanosine 5{prime}-({gamma}-thio)triphosphate (GTP({gamma}S)) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP({gamma}-{sup 35}S) binding sites by 90% and low K{sub m}, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP({gamma}S) was diminished. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low K{sub m} GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor - guanine nucleotide binding protein complex.

Affinity membranes for hormone removal from aqueous solutions

NARCIS (Netherlands)

Urmenyi, A.M.; Poot, Andreas A.; Wessling, Matthias; Mulder, M.H.V.

2005-01-01

A novel affinity membrane was prepared by covalent binding of antibodies (against 17--estradiol) to a micro-porous poly(ethylene vinyl alcohol) (EVAL) membrane, taking benefit from the high surface area of EVAL membranes and the large number of reactive groups available for further surface

VP24-Karyopherin Alpha Binding Affinities Differ between Ebolavirus Species, Influencing Interferon Inhibition and VP24 Stability

Energy Technology Data Exchange (ETDEWEB)

Schwarz, Toni M.; Edwards, Megan R.; Diederichs, Audrey; Alinger, Joshua B.; Leung, Daisy W.; Amarasinghe, Gaya K.; Basler, Christopher F.; Lyles, Douglas S.

2016-12-14

Zaire ebolavirus(EBOV),Bundibugyo ebolavirus(BDBV), andReston ebolavirus(RESTV) belong to the same genus but exhibit different virulence properties. VP24 protein, a structural protein present in all family members, blocks interferon (IFN) signaling and likely contributes to virulence. Inhibition of IFN signaling by EBOV VP24 (eVP24) involves its interaction with the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear transporters. Here, we evaluated eVP24, BDBV VP24 (bVP24), and RESTV VP24 (rVP24) interactions with three NPI-1 subfamily KPNAs (KPNA1, KPNA5, and KPNA6). Using purified proteins, we demonstrated that each VP24 binds to each of the three NPI-1 KPNAs. bVP24, however, exhibited approximately 10-fold-lower KPNA binding affinity than either eVP24 or rVP24. Cell-based assays also indicate that bVP24 exhibits decreased KPNA interaction, decreased suppression of IFN induced gene expression, and a decreased half-life in transfected cells compared to eVP24 or rVP24. Amino acid sequence alignments between bVP24 and eVP24 also identified residues within and surrounding the previously defined eVP24-KPNA5 binding interface that decrease eVP24-KPNA affinity or bVP24-KPNA affinity. VP24 mutations that lead to reduced KPNA binding affinity also decrease IFN inhibition and shorten VP24 half-lives. These data identify novel functional differences in VP24-KPNA interaction and reveal a novel impact of the VP24-KPNA interaction on VP24 stability.

IMPORTANCEThe interaction of Ebola virus (EBOV) VP24 protein with host karyopherin alpha (KPNA) proteins blocks type I interferon (IFN) signaling, which is a central component of the host innate immune response to viral infection. Here, we quantitatively compared the

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.

Multilayer affinity adsorption of albumin on polymer brushes modified membranes in a continuous-flow system.

Science.gov (United States)

Hu, Meng-Xin; Li, Xiang; Li, Ji-Nian; Huang, Jing-Jing; Ren, Ge-Rui

2018-02-23

Polymer brushes modified surfaces have been widely used for protein immobilization and isolation. Modification of membranes with polymer brushes increases the surface concentration of affinity ligands used for protein binding. Albumin is one of the transporting proteins and shows a high affinity to bile acids. In this work, the modified membranes with cholic acid-containing polymer brushes can be facilely prepared by the immobilization of cholic acid on the poly(2-hydroxyethyl methacrylate) grafted microporous polypropylene membranes (MPPMs) for affinity adsorption of albumin. ATR/FT-IR and X-ray photoelectron spectroscopy were used to characterize the chemical composition of the modified membranes. Water contact angle measurements were used to analyze the hydrophilic/hydrophobic properties of the membrane surface. The modified MPPMs show a high affinity to albumin and have little non-specific adsorption of hemoglobin. The dynamic binding capacity of albumin in the continous-flow system increases with the cycle number and feed rate as the binding degree of cholic acid is moderate. The highest binding capacity of affinity membranes is about 52.49 g/m 2 membrane, which is about 24 times more than the monolayer binding capacity. These results reveal proteins could be captured in multilayers by the polymer brushes containing affinity ligands similar to the polymer brushes containing ion-exchange groups, which open up the potential of the polymer brushes containing affinity ligands in protein or another components separation. And the cholic acid containing polymer brushes modified membranes has the promising potential for albumin separation and purification rapidly from serum or fermented solution in medical diagnosis and bioseparation. Copyright © 2018 Elsevier B.V. All rights reserved.

Single-experiment displacement assay for quantifying high-affinity binding by isothermal titration calorimetry.

Science.gov (United States)

Krainer, Georg; Keller, Sandro

2015-04-01

Isothermal titration calorimetry (ITC) is the gold standard for dissecting the thermodynamics of a biomolecular binding process within a single experiment. However, reliable determination of the dissociation constant (KD) from a single titration is typically limited to the range 100 μM>KD>1 nM. Interactions characterized by a lower KD can be assessed indirectly by so-called competition or displacement assays, provided that a suitable competitive ligand is available whose KD falls within the directly accessible window. However, this protocol is limited by the fact that it necessitates at least two titrations to characterize one high-affinity inhibitor, resulting in considerable consumption of both sample material and time. Here, we introduce a fast and efficient ITC displacement assay that allows for the simultaneous characterization of both a high-affinity ligand and a moderate-affinity ligand competing for the same binding site on a receptor within a single experiment. The protocol is based on a titration of the high-affinity ligand into a solution containing the moderate-affinity ligand bound to the receptor present in excess. The resulting biphasic binding isotherm enables accurate and precise determination of KD values and binding enthalpies (ΔH) of both ligands. We discuss the theoretical background underlying the approach, demonstrate its practical application to metal ion chelation, explore its potential and limitations with the aid of simulations and statistical analyses, and elaborate on potential applications to protein-inhibitor interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

Production and Characterization of Desmalonichrome Relative Binding Affinity for Uranyl Ions in Relation to Other Siderophores

Energy Technology Data Exchange (ETDEWEB)

Mo, Kai-For; Dai, Ziyu; Wunschel, David S.

2016-06-24

Siderophores are Fe binding secondary metabolites that have been investigated for their uranium binding properties. Much of the previous work has focused on characterizing hydroxamate types of siderophores, such as desferrioxamine B, for their uranyl binding affinity. Carboxylate forms of these metabolites hold potential to be more efficient chelators of uranyl, yet they have not been widely studied and are more difficult to obtain. Desmalonichrome is a carboxylate siderophore which is not commercially available and so was obtained from the ascomycete fungus Fusarium oxysporum cultivated under Fe depleted conditions. The relative affinity for uranyl binding of desmalonichrome was investigated using a competitive analysis of binding affinities between uranyl acetate and different concentrations of iron(III) chloride using electrospray ionization mass spectrometry (ESI-MS). In addition to desmalonichrome, three other siderophores, including two hydroxamates (desferrioxamine B and desferrichrome) and one carboxylate (desferrichrome A) were studied to understand their relative affinities for the uranyl ion at two pH values. The binding affinities of hydroxymate siderophores to uranyl ion were found to decrease to a greater degree at lower pH as the concentration of Fe (III) ion increases. On the other hand, lowering pH has little impact on the binding affinities between carboxylate siderophores and uranyl ion. Desmalonichrome was shown to have the greatest relative affinity for uranyl at any pH and Fe(III) concentration. These results suggest that acidic functional groups in the ligands are critical for strong chelation with uranium at lower pH.

Definition of percolation thresholds on self-affine surfaces

NARCIS (Netherlands)

Marrink, S.J.; Paterson, Lincoln; Knackstedt, Mark A.

2000-01-01

We study the percolation transition on a two-dimensional substrate with long-range self-affine correlations. We find that the position of the percolation threshold on a correlated lattice is no longer unique and depends on the spanning rule employed. Numerical results are provided for spanning

Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency

DEFF Research Database (Denmark)

Tosco, Paolo; Ahring, Philip K; Dyhring, Tino

2009-01-01

Complementary 3D-QSAR modeling of binding affinity and functional potency is proposed as a tool to pinpoint the molecular features of the ligands, and the corresponding amino acids in the receptor, responsible for high affinity binding vs those driving agonist behavior and receptor activation. Th...

Comment on: Negative ions, molecular electron affinity and orbital structure of cata-condensed polycyclic aromatic hydrocarbons by Rustem V. Khatymov, Mars V. Muftakhov and Pavel V. Shchukin.

Science.gov (United States)

Chen, Edward S; Chen, Edward C M

2018-02-15

The anion mass spectral lifetimes for several aromatic hydrocarbons reported in the subject article were related to significantly different electron affinities. The different values are rationalized using negative ion mass spectral data. Electron affinities for polycyclic aromatic hydrocarbons are reported from the temperature dependence of unpublished electron capture detector data. These are compared with published values and the largest values are assigned to the ground state. The ground state adiabatic electron affinities: (eV) pentacene, 1.41 (3); tetracene, 1.058 (5); benz(a)pyrene, 0.82 (4); benz(a) anthracene, 0.69 (2) anthracene, 0.68 (2); and pyrene, 0.59 (1) are used to assign excited state adiabatic electron affinities: (eV) tetracene: 0.88 (4); anthracene 0.53 (1); pyrene, 0.41 (1); benz(a)anthracene, 0.39 (10); chrysene, 0.32 (1); and phenanthrene, 0.12 (2) and ground state adiabatic electron affinities: (eV) dibenz(a,j)anthracene, 0.69 (3); dibenz(a,h)anthracene, 0.68 (3); benz(e)pyrene, 0.60 (3); and picene, 0.59 (3) from experimental data. The lifetime of benz(a)pyrene is predicted to be larger than 150 μs and for benzo(c)phenanthrene and picene about 40 μs, from ground state adiabatic electron affinities. The assignments of adiabatic electron affinities of aromatic hydrocarbons determined from electron capture detector and mass spectrometric data to ground and excited states are supported by constant electronegativities. A set of consistent ground state adiabatic electron affinities for 15 polycyclic aromatic hydrocarbons is related to lifetimes from the subject article. Copyright © 2017 John Wiley & Sons, Ltd.

Relationship between strains of tumor-bearing animals and the tumor affinity of /sup 169/Yb and /sup 67/Ga

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Hiraki, T [Kanazawa Univ. (Japan). School of Paramedicine; Hisada, K; Ando, I; Ugiie, T

1975-02-01

It is well a well-known fact that ytterbium-169 is a strong bone seeking element. We have already reported that this element was concentrated in nonosseous tumor tissues and that its tumor affinity was stronger than that of gallium-67 in our previous experiment using Yoshida sarcoma-bearing rats. Ytterbium-169 citrate and gallium-67 citrate were compared in four strains of tumor-bearing rats and mice. The uptake rate of ytterbium-169 in tumor tissues was much larger than that of gallium-67 in Ehrlich cancer-bearing mice, but these values of ytterbium-169 were slightly smaller than those of gallium-67 in Yoshida sarcoma-bearing rats, Walker carcinosarcoma 256-bearing rats and sarcoma 180-bearing mice. Tumor to organ ratios of ytterbium-169, which were most important for tumor scanning agents, were much larger than those of gallium-67 in all four strains except for the tumor to bone ratio of ytterbium-169. From the above-described facts, it was shown that ytterbium-169 citrate had a stronger tumor affinity than did gallium-67 citrate and that the tumor affinity of ytterbium-169 citrate was similar in each of these four strains of tumor-bearing animals.

Affinity of four polar neurotransmitters for lipid bilayer membranes

DEFF Research Database (Denmark)

Wang, Chunhua; Ye, Fengbin; Valardez, Gustavo F.

2011-01-01

. The simulations suggest that this attraction mainly relies on electrostatic interactions of the amino group of the neurotransmitter and the lipid phosphate. We conclude that moderate attraction to lipid membranes occurs for some polar neurotransmitters and hence that one premise for a theory of bilayer-mediated......Weak interactions of neurotransmitters and the lipid matrix in the synaptic membrane have been hypothesized to play a role in synaptic transmission of nerve signals, particularly with respect to receptor desensitization (Cantor, R. S. Biochemistry 2003, 42, 11891). The strength of such interactions......, however, was not measured, and this is an obvious impediment for further evaluation and understanding of a possible role for desensitization. We have used dialysis equilibrium to directly measure the net affinity of selected neurotransmitters for lipid membranes and analyzed this affinity data...

Extreme disorder in an ultrahigh-affinity protein complex

Science.gov (United States)

Borgia, Alessandro; Borgia, Madeleine B.; Bugge, Katrine; Kissling, Vera M.; Heidarsson, Pétur O.; Fernandes, Catarina B.; Sottini, Andrea; Soranno, Andrea; Buholzer, Karin J.; Nettels, Daniel; Kragelund, Birthe B.; Best, Robert B.; Schuler, Benjamin

2018-03-01

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.

Momentum conserving defects in affine Toda field theories

Energy Technology Data Exchange (ETDEWEB)

Bristow, Rebecca; Bowcock, Peter [Department of Mathematical Sciences, Durham University,Durham, DH1 3LE (United Kingdom)

2017-05-30

Type II integrable defects with more than one degree of freedom at the defect are investigated. A condition on the form of the Lagrangian for such defects is found which ensures the existence of a conserved momentum in the presence of the defect. In addition it is shown that for any Lagrangian satisfying this condition, the defect equations of motion, when taken to hold everywhere, can be extended to give a Bäcklund transformation between the bulk theories on either side of the defect. This strongly suggests that such systems are integrable. Momentum conserving defects and Bäcklund transformations for affine Toda field theories based on the A{sub n}, B{sub n}, C{sub n} and D{sub n} series of Lie algebras are found. The defect associated with the D{sub 4} affine Toda field theory is examined in more detail. In particular classical time delays for solitons passing through the defect are calculated.

Theory of affine projection algorithms for adaptive filtering

CERN Document Server

Ozeki, Kazuhiko

2016-01-01

This book focuses on theoretical aspects of the affine projection algorithm (APA) for adaptive filtering. The APA is a natural generalization of the classical, normalized least-mean-squares (NLMS) algorithm. The book first explains how the APA evolved from the NLMS algorithm, where an affine projection view is emphasized. By looking at those adaptation algorithms from such a geometrical point of view, we can find many of the important properties of the APA, e.g., the improvement of the convergence rate over the NLMS algorithm especially for correlated input signals. After the birth of the APA in the mid-1980s, similar algorithms were put forward by other researchers independently from different perspectives. This book shows that they are variants of the APA, forming a family of APAs. Then it surveys research on the convergence behavior of the APA, where statistical analyses play important roles. It also reviews developments of techniques to reduce the computational complexity of the APA, which are important f...

Smooth surfaces from bilinear patches: Discrete affine minimal surfaces

KAUST Repository

Kä ferbö ck, Florian; Pottmann, Helmut

2013-01-01

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

Comparing Administrative Satisfaction in Public and Private Higher Education.

Science.gov (United States)

Volkwein, James Fredericks; Parmley, Kelli

This study examined job satisfaction among administrators in public and private higher education. Data on nearly 1,200 administrators, ranging from directors to presidents, was obtained through surveys of 120 public and private universities. It was found that both public and private higher education administrators were most satisfied with the…

Investigating the Relationships between Approaches to Learning, Learner Identities and Academic Achievement in Higher Education

Science.gov (United States)

Herrmann, K. J.; Bager-Elsborg, A.; McCune, V.

2017-01-01

This paper considers relationships between approaches to learning, learner identities, self-efficacy beliefs and academic achievement in higher education. In addition to already established survey instruments, a new scale, "subject area affinity," was developed. The scale explores the extent to which students identify with their area of…

Combinatorial Vector Fields for Piecewise Affine Control Systems

DEFF Research Database (Denmark)

Wisniewski, Rafal; Larsen, Jesper Abildgaard

2008-01-01

This paper is intended to be a continuation of Habets and van Schuppen (2004) and Habets, Collins and van Schuppen (2006), which address the control problem for piecewise-affine systems on an arbitrary polytope or a family of these. Our work deals with the underlying combinatorics of the underlyi...

An Affine Combination of Adaptive Filters for Channels with Different Sparsity Levels

Directory of Open Access Journals (Sweden)

M. Butsenko

2016-06-01

Full Text Available In this paper we present an affine combination strategy for two adaptive filters. One filter is designed to handle sparse impulse responses and the other one performs better if impulse response is dispersive. Filter outputs are combined using an adaptive mixing parameter and the resulting output shows a better performance than each of the combining filters separately. We also demonstrate that affine combination results in faster convergence than a convex combination of two adaptive filters.

Size and shape dependent deprotonation potential and proton affinity of nanodiamond

International Nuclear Information System (INIS)

Barnard, Amanda S; Per, Manolo C

2014-01-01

Many important reactions in biology and medicine involve proton abstraction and transfer, and it is integral to applications such as drug delivery. Unlike electrons, which are quantum mechanically delocalized, protons are instantaneously localized on specific residues in these reactions, which can be a distinct advantage. However, the introduction of nanoparticles, such as non-toxic nanodiamonds, to this field complicates matters, as the number of possible sites increases as the inverse radius of the particle. In this paper we present >10 4 simulations that map the size- and shape-dependence of the deprotonation potential and proton affinity of nanodiamonds in the range 1.8–2.7 nm in average diameter. We find that while the average deprotonation potential and proton affinities decrease with size, the site-specific values are inhomogeneous over the surface of the particles, exhibiting strong shape-dependence. The proton affinity is strongly facet-dependent, whereas the deprotonation potential is edge/corner-dependent, which creates a type of spatial hysteresis in the transfer of protons to and from the nanodiamond, and provides new opportunities for selective functionalization. (paper)

Size and shape dependent deprotonation potential and proton affinity of nanodiamond

Science.gov (United States)

Barnard, Amanda S.; Per, Manolo C.

2014-11-01

Many important reactions in biology and medicine involve proton abstraction and transfer, and it is integral to applications such as drug delivery. Unlike electrons, which are quantum mechanically delocalized, protons are instantaneously localized on specific residues in these reactions, which can be a distinct advantage. However, the introduction of nanoparticles, such as non-toxic nanodiamonds, to this field complicates matters, as the number of possible sites increases as the inverse radius of the particle. In this paper we present \\gt {{10}4} simulations that map the size- and shape-dependence of the deprotonation potential and proton affinity of nanodiamonds in the range 1.8-2.7 nm in average diameter. We find that while the average deprotonation potential and proton affinities decrease with size, the site-specific values are inhomogeneous over the surface of the particles, exhibiting strong shape-dependence. The proton affinity is strongly facet-dependent, whereas the deprotonation potential is edge/corner-dependent, which creates a type of spatial hysteresis in the transfer of protons to and from the nanodiamond, and provides new opportunities for selective functionalization.

Object matching using a locally affine invariant and linear programming techniques.

Science.gov (United States)

Li, Hongsheng; Huang, Xiaolei; He, Lei

2013-02-01

In this paper, we introduce a new matching method based on a novel locally affine-invariant geometric constraint and linear programming techniques. To model and solve the matching problem in a linear programming formulation, all geometric constraints should be able to be exactly or approximately reformulated into a linear form. This is a major difficulty for this kind of matching algorithm. We propose a novel locally affine-invariant constraint which can be exactly linearized and requires a lot fewer auxiliary variables than other linear programming-based methods do. The key idea behind it is that each point in the template point set can be exactly represented by an affine combination of its neighboring points, whose weights can be solved easily by least squares. Errors of reconstructing each matched point using such weights are used to penalize the disagreement of geometric relationships between the template points and the matched points. The resulting overall objective function can be solved efficiently by linear programming techniques. Our experimental results on both rigid and nonrigid object matching show the effectiveness of the proposed algorithm.

Gravitational Goldstone fields from affine gauge theory

Science.gov (United States)

Tresguerres, Romualdo; Mielke, Eckehard W.

2000-08-01

In order to facilitate the application of standard renormalization techniques, gravitation should be described, in the pure connection formalism, as a Yang-Mills theory of a certain spacetime group, say the Poincaré or the affine group. This embodies the translational as well as the linear connection. However, the coframe is not the standard Yang-Mills-type gauge field of the translations, since it lacks the inhomogeneous gradient term in the gauge transformations. By explicitly restoring this ``hidden'' piece within the framework of nonlinear realizations, the usual geometrical interpretation of the dynamical theory becomes possible, and in addition one can avoid the metric or coframe degeneracy which would otherwise interfere with the integrations within the path integral. We claim that nonlinear realizations provide the general mathematical scheme for the foundation of gauge theories of spacetime symmetries. When applied to construct the Yang-Mills theory of the affine group, tetrads become identified with nonlinear translational connections; the anholonomic metric no longer constitutes an independent gravitational potential, since its degrees of freedom reveal a correspondence to eliminateable Goldstone bosons. This may be an important advantage for quantization.

Hexachlorobenzene stimulates uroporphyria in low affinity AHR mice without increasing CYP1A2

International Nuclear Information System (INIS)

Gorman, Nadia; Trask, Heidi S.; Robinson, Susan W.; Sinclair, Jacqueline F.; Gerhard, Glenn S.; Smith, Andrew G.; Sinclair, Peter R.

2007-01-01

Hexachlorobenzene (HCB), a weak ligand of the aryl hydrocarbon receptor (AHR), causes hepatic uroporphyrin (URO) accumulation (uroporphyria) in humans and animals. CYP1A2 has been shown to be necessary in the development of uroporphyria in mice. Using mice expressing the low affinity form of the AH receptor (AHRd), we investigated whether the enhancement of uroporphyria by HCB involves an obligatory increase in CYP1A2 as measured by specific enzyme assays and immunoblotting. We compared the ability of HCB, in combination with iron dextran and the porphyrin precursor, 5-aminolevulinate (ALA), to cause uroporphyria in a strain of mice (C57BL/6) which expresses the high affinity form of the receptor (AHRb 1 ), with three strains of mice (SWR and two 129 sublines) expressing the low affinity AHRd. In C57BL/6 mice, HCB-enhanced uroporphyria was associated with a doubling of CYP1A2. HCB treatment produced uroporphyria in iron-loaded mice expressing AHRd, even though there was little or no increase in CYP1A2. Cyp1a2(-/-) mice in a 129 background were completely resistant to HCB-induced uroporphyria, and female Hfe(-/-) 129 mice, in which the levels of hepatic CYP1A2 were half of those of the male levels, responded poorly. The effect of exogenous iron, administered in the form of iron dextran, on HCB enhancement of uroporphryia could be replicated utilizing the endogenous hepatic iron accumulated in 129 Hfe(-/-) mice. In conclusion, some minimal basal expression of CYP1A2 is essential for HCB-mediated enhancement of uroporphyria, but increases in CYP1A2 above that level are not essential

Removal of an endogenous antigen from an antibody to increase its effective affinity constant, as illustrated by Triiodothyronine assay

International Nuclear Information System (INIS)

Oliver, L.K.; Cano, C.

1977-01-01

Antisera to triiodothyronine were shown to contain large quantities of the hormone, well in excess of normal circulating concentrations. Extracting the triiodothyronine from the antiserum with alkaline ethanol yielded an antibody of increased affinity. Use of this antibody in a radioimmunoassay resulted in a fourfold increase in sensitivity as compared with the unextracted material

Distribution, habitat affinities and phenology of the Micrargus herbigradus-species group (Araneae: Linyphiidae) in Poland.

Science.gov (United States)

Wiśniewski, Konrad; Rozwałka, Robert; Wesołowska, Wanda

2018-01-01

We review the known information on the distribution and habitat affinities of the Micrargus herbigradus -species group in Poland. The analysis is based on a thorough literature survey, our own materials, and verification of some older collections. We give new diagnostic drawings and review the characters that are useful in identification of species within the group. Three species are present in Poland: M. herbigradus (Blackwall, 1854), M. apertus (O.-P. Cambridge, 1870) and M. georgescuae Millidge, 1976. The latter is recorded for the first time in the country, and we add numerous new localities for the two former species. Micrargus herbigradus is common and widespread in Poland, living in various habitats, with only a slight preference to forests. In contrast, M. apertus is widely distributed but rarely found, while its affinity to forests is the highest within the group. The records of this species are most numerous in lowland forests (up to c. 300 m a.s.l), but it can also be found at higher altitudes. M. georgescuae is found only in montane habitats, both in the Sudetes and the Carpathian Mountains, from above 650 m a.s.l. The adults of all three species occur the whole year round, but seem to be most abundant in May and June.

Epitope structure and binding affinity of single chain llama anti-β-amyloid antibodies revealed by proteolytic excision affinity-mass spectrometry.

Science.gov (United States)

Paraschiv, Gabriela; Vincke, Cécile; Czaplewska, Paulina; Manea, Marilena; Muyldermans, Serge; Przybylski, Michael

2013-01-01

ß-Amyloid (Aß) immunotherapy has become a promising strategy for reducing the level of Aß in brain. New immunological approaches have been recently proposed for rapid, early diagnosis, and molecular treatment of neurodegenerative diseases related to Alzheimer's Disease (AD). The combination of proteolytic epitope excision and extraction and mass spectrometry using digestion with various proteases has been shown to be an efficient tool for the identification and molecular characterization of antigenic determinants. Here, we report the identification of the Aβ epitope recognized by the variable domain of single chain llama anti-Aβ-antibodies, termed Aβ-nanobodies, that have been discovered in the blood of camelids and found to be promising candidates for immunotherapy of AD. The epitope recognized by two Aβ-specific nanobodies was identified by proteolytic epitope extraction- and excision-mass spectrometry using a series of proteases (trypsin, chymotrypsin, GluC-protease, and LysC-protease). Matrix-assisted laser desorption ionization--mass spectrometric analysis of the affinity--elution fraction provided the epitope, Aβ(17-28), in the mid- to carboxy-terminal domain of Aβ, which has been shown to exert an Aß-fibril inhibiting effect. Affinity studies of the synthetic epitope confirmed that the Aβ(17-28) peptide is the minimal fragment that binds to the nanobodies. The interactions between the nanobodies and full length Aβ(1-40) or Aβ-peptides containing or lacking the epitope sequence were further characterized by enzyme linked immunosorbent assay and bioaffinity analysis. Determinations of binding affinities between the Aβ-nanobodies and Aβ(1-40) and the Aβ(17-28) epitope provided K(D) values of approximately 150 and 700 nmol, respectively. Thus, the knowledge of the epitope may be highly useful for future studies of Aβ-aggregation (oligomerization and fibril formation) and for designing new aggregation inhibitors. Copyright © 2012 John Wiley

Ribosomal binding region for the antibiotic tiamulin: stoichiometry, subunit location, and affinity for various analogs.

Science.gov (United States)

Högenauer, G; Ruf, C

1981-01-01

Equilibrium dialysis experiments with a highly purified preparation of labeled tiamulin, a semisynthetic derivative of the antibiotic pleuromutilin, and Escherichia coli ribosomes allowed the determination of two binding sites for the drug. The binding reaction showed a cooperative effect. Of the two subunits, the 50S particle was able to bind the antibiotic in a 1:1 stoichiometry. Hence, the 50S subunit contributed predominantly to the binding energy which held the antibiotic to the ribosomes. The 30S subunit, showing no strong affinity for the drug, may be needed for the generation of the second binding site in the 70S particle. If depleted of ammonium ions, 70S ribosomes lost their binding capacity for the antibiotic. The attachment sites for tiamulin could be restored by heating the ribosomes to 40 degrees C in the presence of either ammonium ions or the antibiotic. Other pleuromutilin derivatives displaced labeled tiamulin from its ribosomal binding sites. By quantifying this competition, the relative affinity of various pleuromutilin derivatives for E. coli ribosomes was determined. The binding correlated with the minimal inhibitory concentrations of these compounds against E. coli. When compared with the minimal inhibitory concentrations of these compounds against E. coli. When compared with the minimal inhibitory concentrations against E. coli. When compared with the minimal inhibitory concentrations against Staphylococcus aureus, the correlation was less strict, but the same trend prevailed. These results suggest that the antibacterial activities of various pleuromutilin derivatives on a given test organism are mainly determined by the strength of binding to the ribosomes within the bacterial cell. PMID:6751216

Affinity-seeking, social loneliness, and social avoidance among Facebook users.

Science.gov (United States)

Lemieux, Robert; Lajoie, Sean; Trainor, Nathan E

2013-04-01

This study explored the relations between use of the social networking site Facebook and scores on affinity-seeking, social loneliness, and social avoidance by 313 college students. Social loneliness and social avoidance, but not affinity-seeking, were positively and statistically significantly related to time spent using Facebook. The number of close Facebook friends was negatively and statistically significantly related to social loneliness and social avoidance. Women perceived Facebook as a more integral part of daily interactions than did men. 38% of the 283 Facebook members indicated their accounts contained information and/or a picture that could embarrass them, with men having significantly more embarrassing content than women. The findings are discussed within the context of social compensation.

A Contingent Affinity: Max Weber, Carl Schmitt, and the Challenge of Modern Politics.

Science.gov (United States)

Magalhães, Pedro T

2016-01-01

The thesis that the theory of charismatic-plebiscitary democracy developed by Max Weber in the wake of the Weimar Republic was developed to its ultimate consequences by Carl Schmitt in the final crisis of Weimar has been hotly debated since it was first advanced in the 1950s. This paper proposes a fresh look at the controversy. By comparing both authors' concepts of politics in their relation to the problem of modernity, it argues that the Weber-Schmitt affair is neither a baseless legend nor a case of natural continuity. Instead, it should rather be understood in terms of a contingent affinity.

Higher Education and Efficiency in Europe: A Comparative Analysis

Science.gov (United States)

Sánchez-Pérez, Rosario

2012-01-01

This paper analyses the efficiency of higher education in equalizing the feasible wages obtained for men and women in the labour market. To do that, It is estimated two stochastic frontiers. The first one measures the effect of higher education inside the group of men and women for six European countries. The results indicate that in Denmark,…

Higher fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tuberculous compared to bacterial spondylodiscitis

Energy Technology Data Exchange (ETDEWEB)

Bassetti, Matteo; Merelli, Maria; Della Siega, Paola; Righi, Elda [Santa Maria della Misericordia University Hospital, Infectious Diseases Division, Udine (Italy); Di Gregorio, Fernando [Santa Maria della Misericordia University Hospital, Microbiology Unit, Udine (Italy); Screm, Maria; Scarparo, Claudio [Santa Maria della Misericordia University Hospital, Radiology Unit, Udine (Italy)

2017-06-15

Tuberculous spondylodiscitis can be difficult to diagnose because of its nonspecific symptoms and the similarities with non-tubercular forms of spinal infection. Fluorine-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is increasingly used for the diagnosis and monitoring of tubercular diseases. Retrospective, case-control study comparing tuberculous spondylodiscitis with biopsy-confirmed pyogenic spondylodiscitis in the period 2010-2012. Ten cases of tuberculous spondylodiscitis and 20 controls were included. Compared to pyogenic, tuberculous spondylodiscitis was more frequent in younger patients (P = 0.01) and was more often associated with thoraco-lumbar tract lesions (P = 0.01) and multiple vertebral involvement (P = 0.01). Significantly higher maximum standardized uptake values (SUV) at FDG-PET were displayed by tuberculous spondylodiscitis compared to controls (12.4 vs. 7.3, P = 0.003). SUV levels above 8 showed the highest value of specificity (0.80). Mean SUV reduction of 48% was detected for tuberculous spondylodiscitis at 1-month follow-up. Higher SUV levels at FDG-PET were detected in tuberculous compared with pyogenic spondylodiscitis. PET-CT use appeared useful in the disease follow-up after treatment initiation. (orig.)

Enhancement of the cytotoxicity of radiosensitizers by modest hyperthermia: the electron-affinity relationship

Energy Technology Data Exchange (ETDEWEB)

Rajaratnam, S.; Adams, G.E.; Stratford, I.J.; Clarke, C.

1982-01-01

The cytotoxicity of 3 electron-affinic radiosensitizers has been studied in Chinese hamster V-79 cells as a function of pH and modest hyperthermia. When equitoxic concentrations were used and temperature was increased from 34 to 41/sup 0/C metronidazole, the compound with the lowest electron affinity showed the greatest enhancement of hypoxic-cell toxicity, and nitrofurantoin, the compound with the highest electron affinity, the least. The results can be explained if the mechanisms of toxicity involves a redox reaction, since it would be expected that the least toxic compound (lowest electron affinity) would have the largest activation energy and hence the greatest temperature effect. This appears to hold for these 3 compounds. Experiments also showed that nitrofurantoin which exhibits no increase in toxicity when the temperature was increased from 37 to 41/sup 0/C at pH 7.4, showed an increase in toxicity for the same temperature change at the pH of 7.0 and 6.6. Under aerobic conditions only metronidazole showed significant toxicity at 41/sup 0/C, where the differential between aerobic and hypoxic cell toxicity was minimal, both at pH 7.4, and at the low pH values of 7.0 and 6.6. In the clinical setting there is evidence that tumor cells are at a lower pH than their surrounding normal tissues. Hypoxic-cell cytotoxicity is enhanced at low pH, and even further enhanced at low pH in combination with a temperature of 41/sup 0/C. However, this finding correlates conversely with electron affinity.

Synthesis of E7 peptide-modified biodegradable polyester with the improving affinity to mesenchymal stem cells

International Nuclear Information System (INIS)

Li, Qian; Xing, Dongming; Ma, Lie; Gao, Changyou

2017-01-01

As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between L-lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine. - Highlights: • P(MTMC-LA) was synthesized through ring-opening copolymerization and retro Diels-Alder reaction. • P(MTMC-LA) was modified by dBMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry. • E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation.

Synthesis of E7 peptide-modified biodegradable polyester with the improving affinity to mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Li, Qian; Xing, Dongming; Ma, Lie, E-mail: liema@zju.edu.cn; Gao, Changyou

2017-04-01

As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between L-lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine. - Highlights: • P(MTMC-LA) was synthesized through ring-opening copolymerization and retro Diels-Alder reaction. • P(MTMC-LA) was modified by dBMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry. • E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation.

A Quick and Affine Invariance Matching Method for Oblique Images

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XIAO Xiongwu

2015-04-01

Full Text Available This paper proposed a quick, affine invariance matching method for oblique images. It calculated the initial affine matrix by making full use of the two estimated camera axis orientation parameters of an oblique image, then recovered the oblique image to a rectified image by doing the inverse affine transform, and left over by the SIFT method. We used the nearest neighbor distance ratio(NNDR, normalized cross correlation(NCC measure constraints and consistency check to get the coarse matches, then used RANSAC method to calculate the fundamental matrix and the homography matrix. And we got the matches that they were interior points when calculating the homography matrix, then calculated the average value of the matches' principal direction differences. During the matching process, we got the initial matching features by the nearest neighbor(NN matching strategy, then used the epipolar constrains, homography constrains, NCC measure constrains and consistency check of the initial matches' principal direction differences with the calculated average value of the interior matches' principal direction differences to eliminate false matches. Experiments conducted on three pairs of typical oblique images demonstrate that our method takes about the same time as SIFT to match a pair of oblique images with a plenty of corresponding points distributed evenly and an extremely low mismatching rate.

Inverse scattering and solitons in An-1 affine Toda field theories

International Nuclear Information System (INIS)

Beggs, E.J.; Johnson, P.R.

1997-01-01

We implement the inverse scattering method in the case of the A n affine Toda field theories, by studying the space-time evolution of simple poles in the underlying loop group. We find the known single-soliton solutions, as well as additional solutions with non-linear modes of oscillation around the standard solution, by studying the particularly simple case where the residue at the pole is a rank-one projection. We show that these solutions with extra modes have the same mass and topological charges as the standard solutions, so we do not shed any light on the missing topological charge problem in these models. From the monodromy matrix it is shown that these solutions have the same higher conserved charges as the standard solutions. We also show that the integrated energy-momentum density can be calculated from the central extension of the loop group. (orig.)

Preparation and characterization of fluorophenylboronic acid-functionalized affinity monolithic columns for the selective enrichment of cis-diol-containing biomolecules.

Science.gov (United States)

Li, Qianjin; Liu, Zhen

2015-01-01

Boronate affinity monolithic columns have been developed into an important means for the selective recognition and capture of cis-diol-containing biomolecules, such as glycoproteins, nucleosides and saccharides. The ligands of boronic acids are playing an important role in boronate affinity monolithic columns. Although several boronate affinity monoliths with high affinity toward cis-diol-containing biomolecules have been reported, only few publications are focused on their detailed procedures for preparation and characterization. This chapter describes in detail the preparation and characterization of a boronate affinity monolithic column applying 2,4-difluoro-3-formyl-phenylboronic acid (DFFPBA) as a ligand. The DFFPBA-functionalized monolithic column not only exhibited an ultrahigh boronate affinity toward cis-diol-containing biomolecules, but also showed great potential for the selective enrichment of cis-diol-containing biomolecules in real samples.

An affine model of the dynamics of astrophysical discs

Science.gov (United States)

Ogilvie, Gordon I.

2018-06-01

Thin astrophysical discs are very often modelled using the equations of 2D hydrodynamics. We derive an extension of this model that describes more accurately the behaviour of a thin disc in the absence of self-gravity, magnetic fields, and complex internal motions. The ideal fluid theory is derived directly from Hamilton's Principle for a 3D fluid after making a specific approximation to the deformation gradient tensor. We express the equations in Eulerian form after projection on to a reference plane. The disc is thought of as a set of fluid columns, each of which is capable of a time-dependent affine transformation, consisting of a translation together with a linear transformation in three dimensions. Therefore, in addition to the usual 2D hydrodynamics in the reference plane, the theory allows for a deformation of the mid-plane (as occurs in warped discs) and for the internal shearing motions that accompany such deformations. It also allows for the vertical expansions driven in non-circular discs by a variation of the vertical gravitational field around the horizontal streamlines, or by a divergence of the horizontal velocity. The equations of the affine model embody conservation laws for energy and potential vorticity, even for non-planar discs. We verify that they reproduce exactly the linear theories of 3D warped and eccentric discs in a secular approximation. However, the affine model does not rely on any secular or small-amplitude assumptions and should be useful in more general circumstances.

Affinity-tuning leukocyte integrin for development of safe therapeutics

Science.gov (United States)

Park, Spencer

Much attention has been given to the molecular and cellular pathways linking inflammation with cancer and the local tumor environment to identify new target molecules that could lead to improved diagnosis and treatment. Among the many molecular players involved in the complex response, central to the induction of inflammation is intercellular adhesion molecule (ICAM)-1, which is of particular interest for its highly sensitive and localized expression in response to inflammatory signals. ICAM-1, which has been implicated to play a critical role in tumor progression in various types of cancer, has also been linked to cancer metastases, where ICAM-1 facilitates the spread of metastatic cancer cells to secondary sites. This unique expression profile of ICAM-1 throughout solid tumor microenvironment makes ICAM-1 an intriguing molecular target, which holds great potential as an important diagnostic and therapeutic tool. Herein, we have engineered the ligand binding domain, or the inserted (I) domain of a leukocyte integrin, to exhibit a wide range of monovalent affinities to the natural ligand, ICAM-1. Using the resulting I domain variants, we have created drug and gene delivery nanoparticles, as well as targeted immunotherapeutics that have the ability to bind and migrate to inflammatory sites prevalent in tumors and the associated microenvironment. Through the delivery of diagnostic agents, chemotherapeutics, and immunotherapeutics, the following chapters demonstrate that the affinity enhancements achieved by directed evolution bring the affinity of I domains into the range optimal for numerous applications.

Modulating uranium binding affinity in engineered calmodulin EF-hand peptides: effect of phosphorylation.