308 research outputs found
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Characterization of Binding Interactions Between Heparin, and Peptides and Peptidomimetics
No full textABSTRACT OF THE DISSERTATIONCharacterization of Binding Interactions Between Heparin, and Peptides and PeptidomimeticsByMark HamzaDoctor of Philosophy, Graduate Program in ChemistryUniversity of California, Riverside, June 2010Dr. Dallas L. Rabenstein, Chairperson The aim of this work is to determine the feasibility of peptides and/or peptidomimetics, such as peptoids and peptide/peptoid hybrids, as suitable replacements for Protamine, a drug used to inactivate heparin's anticoagulant activity. Heparin is administered to prevent blood coagulation during certain medical procedures, such as cardiopulmonary bypass. Heparin prevents coagulation by forming a complex with antithrombin, a serine protease inhibitor, thereby accelerating antithrombin's activity. Protamine is then used to restore the coagulation cascade by displacing heparin from antithrombin forming a heparin-Protamine complex. As Protamine has exhibited detrimental side-effects during its administration, this work has endeavored to design a safer alternative. Several methods have been implemented to characterize the binding interaction between heparin, and the peptides and peptidomimetics developed in this work: (i) isothermal titration calorimetry was utilized to acquire a quantitative binding constant which demonstrated that some of the peptides and peptidomimetics exhibit a high heparin-binding affinity which is critical to displace heparin from antithrombin; (ii) heparin affinity chromatography was used to determine a relative heparin-binding affinity between peptides and peptidomimetics for which a quantitative binding constant could not be measured due to weak heparin-binding interactions; (iii) secondary structure of peptides and peptidomimetics was ascertained by circular dichroism. The compounds synthesized in this work were observed to conform to either a polyproline I-type or polyproline II-type helical secondary structure. Establishing secondary structure is a vital factor in the rational design of heparin-binding peptides and peptidomimetics. The results of this work show that peptides and peptidomimetics can be rationally designed so as to bind heparin with high affinity. This is an important step in demonstrating that the peptides and peptidomimetics designed in this work have the potential to replace Protamine as an antagonist to heparin
l castello di Rabenstein e la comunità di Montenars: un feudo Prampero
No full textNel volume sono ripercorse le vicende del castello di Rabenstein sia la storia della comunità di Montenars nella sua interezza prendendo in esame il rapporto con i giurisdicenti Prampero, la società e le condizioni economiche, l’emigrazione verso i paesi della pianura, le forme giuridiche del potere, le strutture familiari, le relazioni commerciali e finanziarie con la vicina Gemona e la vita religiosa, dagli eventi che portarono all’autonomia della Chiesa di Sant’Elena dalla pieve di Artegna alle modalità di sfruttamento del patrimonio, nell’intento di ricostruire nel modo più completo possibile quella che fu la Montenars dalla metà del Duecento circa alla prima età moderna
Differenz- und Normalitätskonstruktionen reflektieren. Perspektiven für eine Lehrerinnen- und Lehrerbildung für Schule und Unterricht im Anspruch von Inklusion
No full textTervooren A, Rabenstein K, Gottuck S, Marian L. Differenz- und Normalitätskonstruktionen reflektieren. Perspektiven für eine Lehrerinnen- und Lehrerbildung für Schule und Unterricht im Anspruch von Inklusion. In: Bundesministerium für Bildung und Forschung (BMBF), ed. Perspektiven für eine gelingende Inklusion. Beiträge der „Qualitätsoffensive Lehrerbildung“ für Forschung und Praxis. Berlin: BMBF ; 2018: 11-21
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Proton NMR Studies of the Interaction of Heparin-Derived Oligosaccharide with Biological Molecules and the Cis/Trans Isomerization of Amide Bonds in Peptides and Peptide/Peptoid Hybrids
No full textABSTRACT OF THE DISSERTATIONProton NMR Studies of the Interaction of Heparin-Derived Oligosaccharide with Biological Molecules and the Cis/Trans Isomerization of Amide Bonds in Peptides and Peptide/Peptoid HybridsByKhanh Trong NguyenDoctor of Philosophy, Graduate Program in ChemistryUniversity of California, Riverside, March 2009Professor Dallas L. Rabenstein, Chairperson Two diverse topics in biological chemistry are the subject of this dissertation. In part I, the research focuses on heparin and the interaction of histidine-containing peptides with heparin. Heparin is a linear polysaccharide, which is formed through the linkage of variously sulfated uronic acid-(14)-D-glucosamine repeating disaccharide subunits by glycosidic bonds. The structure of heparin is not yet completely understood due to its extreme complexity. Consequently, details of the binding of peptides and proteins by heparin is not well understood. One approach is to use well-defined heparin-derived oligosaccharides with different structures as models to probe the question of specificity of binding.Three heparin-derived tetrasaccharides, one hexasaccharide and one octasaccharide were isolated, purified and characterized. A structurally defined tetrasaccharide was then used as a model to study heparin binding by histidine-containing peptides and related molecules. The imidazolium group of all the molecules studied was found to bind site specifically to a binding pocket formed by an iduronic acid-glucosamine-iduronic acid trisaccharide sequence. Binding constants were determined for the complexes by NMR. Binding constants and relative binding affinities were also determined for the binding of the same molecules by intact heparin by isothermal titration calorimetry and heparin affinity chromatography, respectively. In part II, the kinetics and thermodynamics of cis/trans isomerization of Xaa-sarcosine tertiary amide bonds in peptide/peptoid hybrids were studied. Xaa represents an amino acid and sarcosine is N-methyl glycine. Specifically, the affect of amino acid sequence on the kinetics and equilibria of cis/trans isomerization across Xaa-sarcosine peptide bonds in three series of peptide/peptoid hybrids having the sequences Ac-Cys-Sar-His-Xaa-(Ala)3-Cys-NH2, where Xaa is His, Gly, Lys, Phe, Asp and Glu, Ac-Cys-Sar-(Ala)x-His-(Ala)y-Cys-NH2, x = 0-4 and y = 4-0, and Ac-Cys-Sar-His-(Ala)3-Cys-NH2, Ac-Cys-His-Sar-(Ala)3-Cys-NH2, etc., were studied. The populations of the cis and trans isomers and the kinetics of cis/trans interconversion were found to depend on the amino acid preceding sarcosine.The kinetics and equilibria of cis/trans isomerization across the Xaa-Xaa secondary amide bonds in a series of peptides of the sequence Ac-Cys-Xaa-Xaa-Cys-His-NH2, where Xaa is Ala, Tyr and Phe, were also studied. These peptides were studied as model peptides for oxido-reductase enzymes with the Cys-Xaa-Xaa-Cys motif. The effects of the type and position of the central Xaa residues on the kinetics and equilibria of cis/trans isomerization were examined. Rate and equilibrium constants for cis/trans isomerization together with thermodynamic parameters were determined for all the peptides and peptide/peptoid hybrids studied in both their dithiol and disulfide forms. Rate constants for interconversion between the cis and trans configurational isomers were determined by inversion-magnetization transfer NMR methods and equilibrium constants for the cis/trans isomerization were determined from resonance intensities
Die Herstellung einer gemeinsamen Ordnung am Schulanfang. Eine Rekonstruktion an einem Beispiel aus dem Morgenkreis
No full textKatenbrink N, Wagener U. Die Herstellung einer gemeinsamen Ordnung am Schulanfang. Eine Rekonstruktion an einem Beispiel aus dem Morgenkreis. In: Rabenstein K, Wicke L, eds. Die Schulklasse – kein Gegenstand qualitativer Schulforschung? Theoretische Perspektiven, empirische Einblicke und methodologische Diskussionen zur Konstitution der Schulklasse. Verlag Julius Klinkhardt; 2024: 95-110.Eine Schulklasse stellt zunächst einen organisatorisch hergestellten Interak-
tionsraum dar, in dem sich Unterricht vollziehen kann. Aus praxeologischer
Perspektive konstituiert sich dieser Raum durch Praktiken, durch die eine
gemeinsame Ordnung hervorgebracht und bearbeitet wird. So bilden Schul-
klassen spezifische Leistungsordnungen oder Klassenidentitäten aus. Wie diese
gemeinsame Ordnung in einer jahrgangsübergreifenden Schuleingangsstufe,
die ca. zur Hälfte aus neuen Schüler*innen besteht, im Morgenkreis hervor-
gebracht wird und wie sich wiederum die einzelnen Schüler*innen zu dieser
Ordnung und innerhalb dieser gemeinsamen Ordnung positionieren, wird
hier im Folgenden rekonstruktiv nachgezeichne
Kamerad*innen, Peers oder Freunde? Organisationstheoretische Reflexionen der Schulklasse am Beispiel des Abschreibens
No full textGoldmann D, Katenbrink N. Kamerad*innen, Peers oder Freunde? Organisationstheoretische Reflexionen der Schulklasse am Beispiel des Abschreibens. In: Rabenstein K, Wicke L, eds. Die Schulklasse – kein Gegenstand qualitativer Schulforschung? Theoretische Perspektiven, empirische Einblicke und methodologische Diskussionen zur Konstitution der Schulklasse. Verlag Julius Klinkhardt; 2024: 164-181.Anstatt von Schüler*innen von Peers zu sprechen, wenn sie von den schuli-
schen Erwartungen abweichen oder diesen zuwiderhandeln, schlägt der Beitrag
den Begriff der Kameradschaft unter Schüler*innen vor. Damit wird das abwei-
chende Verhalten der Schüler*innen nicht einer der Schule äußerlichen Welt
wie z. B. einer Jugendkultur zugeschrieben oder ihr Ursprung ungeklärt gelas-
sen, sondern über eine organisationstheoretische Rahmung als typisch kollegia-
les bzw. kameradschaftliches Verhalten verstanden, das in allen Organisationen
beobachtbar ist. Die Schulklasse kann damit als Paradefall für organisationale
Untereinheiten und ihre Beziehungsstrukturen gesehen werden. Dies wird an-
hand von empirischen Schüler*innenkommentierungen zum Abschreiben von
Hausaufgaben verdeutlicht. Darin dokumentiert sich die Schulklasse als Soli-
dargemeinschaft, in der jede*r inkludiert ist und die von allen Schüler*innen
gleichermaßen getragen wird. Da somit Abschreiben nicht nur nachträglich für
die schulischen Ziele sind, sondern auch einen Beitrag für das schulische Inter-
esse an Gemeinschaftsbildung darstellt, kann das Abschreiben für die Schule –
und nicht nur aus der Perspektive der Schüler*innen – als nützlich und somit
als ‚brauchbare Illegalität‘ verstanden werde
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The Design, Synthesis and Evaluation of Peptoid Heparin Inhibitors
No full textThe Design and Evaluation of Peptoid Heparin InhibitorsByBruce K. FordDoctor of Philosophy, Graduate Program in ChemistryUniversity of California, Riverside, August 2011Dr. Dallas Rabinstein, Chairperson Heparin has found use as an anticoagulant in medicine for more than 70 years1 and also plays important biological roles in addition to its involvement in the inhibition of the coagulant cascade. Since human blood has a tendency to clot in direct contact with plastics, intravenous lines are coated with heparin to inhibit coagulation during surgery, or in kidney dialysis and in other medical situations where blood is circulated extracorporeally, where it comes into direct contact with synthetic materials. Also heparan sulfate is added to the intravenous blood supply for the same purpose. Following a medical procedure of this type, it is nessary to reverse the effects of the heparin and heparan sulfate. Currently is the only substances available for this purpose. Protamine is derived from natural sources and possesses imunogenic effects. In this study, a series of peptoids, which are analogs of peptides, have been designed, synthesized2 and studied with the goal of producing molecules with high binding affinity to heparin. The peptoids were produced through a solid phase synthesis methodology using a two step submonomer procedure to create each peptoid monomer unit, which were then joined together to produce a library of 18 peptoid analogs. These peptoids were designed and synthesized with amine bearing side chains strategically located along the peptoid sequence , resulting in cationic peptoids at neutral pH. The amine side chains were also converted to guanidium groups post synthesis of the peptoid oligomers to yield a second family of cationic peptoids that are analogs of arginine containing peptides. Upon synthesis of these two related libraries of peptoids, they were studied using a variety of methods including Isothermal Titration Calormemitry, Heparin Affinity Chromatography, TOF-Maldi MS, and Circular Dichroism. The results of these studies indicated that it is possible to synthesize high-binding affinity peptoids to heparin. It is hoped that these peptoids, by binding tightly with heparin could potentially replace the too often immunogenic side effects of protamine currently in use in medicine today. References1. Folkman, J., Langer, R., Linhardt, R. J., Haudenschild, C.,Taylor, S. Science 1983, 221, 719-725.2. Zuckermann, R. N., Kerr, J.M., Kent, S.B, Moos, W.H. J. Am. Chem. Soc. 1992, 114, 10646-10647
Binding of the growth factor glycyl-l-histidyl-l-lysine by heparin
No full textAbstractEvidence is presented that the growth factor glycylhistidyl-lysine (GHK) binds to heparin, and the interaction has been characterized by [1H]NMR spectroscopy. 1H chemical shifts indicate that GHK interacts with both the carboxylic acid and the carboxylate forms of heparin. The chemical shift data are consistent with a weak delocalized binding of the triprotonated (ImH+, GlyNH3+, LysNH3+) form of GHK by the carboxylic acid form of heparin. As the pD is increased and the carboxylic acid groups are titrated, chemical shift data indicate that ammonium groups of GHK are hydrogen bonded to heparin carboxylate groups, while the histidyl imidazolium ring occupies the imidazolium-binding site of heparin. Evidence for site-specific binding includes displacement of chemical shift titration curves for heparin to lower pD, increased shielding of specific heparin protons by the imidazolium ring current and displacement of chemical shift titration curves for GHK to higher pD. Specific binding constants were determined for binding of the (ImH+, GlyNH3+), LysNH3+), (ImH+, GlyNH2, LysNH3+) and (Im, GlyNH3+, LysNH3+) forms of GHK by the carboxylate form of heparin from chemical shift vs. pD titration data
Efficient Implementations of Complex and Real Valued Filter Banks for Comparative Subband Processing with an Application to Adaptive Filtering (301kB)
No full textIn this paper, we discuss efficient methods to implement correlation type algorithms in subbands. Based on a polyphase representation, a modulated GDFT filter bank with arbitrary integer decimation ratio can be performed at minimum cost, yielding complex subband signals. Real valued subbands can be achieved by appropriate postprocessing of the complex filter bank. Algorithm specific, complex or real implementation may be better suited, for which we present criteria. For the example of subband adaptive filtering as applied in acoustic echo cancellation, we compare a number of algorithms with respect to their best implementation
Performance Limitation of Subband Adaptive Equalisers
No full textThe aim of this reported work was identifying and quantifying limitation for the subband adaptive equalisers. The derived Wiener solution is compared against simulations for the subband equaliser, and it is verified that aliasing caused in the subband decimation can be considered equivalent to channel noise. Finally, how this limitation can be mitigated by careful system design is discussed
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