Cyclic creep buckling of integrally stiffened aluminum alloy panels

ASTIA Document no. AD 155834.

Drawdown in wells responding to cyclic pumping /

Mode of access: Internet.

Performance of 1/3-scale model precast concrete beam-column connections subjected to cyclic inelastic loads : report no. 4 /

Mode of access: Internet.

Groups of order pm which contain cyclic subgroups of order pm-3,

Mode of access: Internet.

A compilation and analysis of cyclic triaxial test data /

Mode of access: Internet.

Irreducible cyclic presentations of the trivial group

We produce families of irreducible cyclic presentations of the trivial group. These families comprehensively answer questions about such presentations asked by Dunwoody and by Edjvet, Hammond, and Thomas. Our theorems are purely theoretical, but their derivation is based on practical computations. We explain how we chose the computations and how we deduced the theorems.

Mode Localization in a Nearly Cyclic Symmetric System

Thesis (Ph.D.)--University of Washington, 2016-06

Difficult macrocyclizations: New strategies for synthesizing highly strained cyclic tetrapeptides

Cyclic tetrapeptides are an intriguing class of natural products. To synthesize highly strained cyclic tetrapeptides; we developed a macrocyclization strategy that involves the inclusion of 2-hydroxy-6-nitrobenzyl (HnB) group at the N-terminus and in the middle of the sequence. The N-terminal auxiliary performs a ring closure/ring contraction role, and the backbone auxiliary promotes cis amide bonds to facilitate the otherwise difficult ring contraction. Following this route, the all-L cyclic tetrapeptide cyclo-[Tyr-Arg-Phe-Ala] was successfully prepared.

Designing supramolecular structures from models of cyclic peptide scaffolds with heterocyclic constraints

Cyclic peptides containing oxazole and thiazole heterocycles have been examined for their capacity to be used as scaffolds in larger, more complex, protein-like structures. Both the macrocyclic scaffolds and the supramolecular structures derived therefrom have been visualised by molecular modelling techniques. These molecules are too symmetrical to examine structurally by NMR spectroscopy. The cyclic hexapeptide ([Aaa-Thz](3), [Aaa-Oxz](3)) and cyclic octapeptide ([Aaa-Thz](4), [Aaa-Oxz](4)) analogues are composed of dipeptide surrogates (Aaa: amino acid, Thz: thiazole, Oxz: oxazole) derived from intramolecular condensation of cysteine or serine/threonine side chains in dipeptides like Aaa-Cys, Aaa-Ser and Aaa-Thr. The five-membered heterocyclic rings, like thiazole, oxazole and reduced analogues like thiazoline, thiazolidine and oxazoline have profound influences on the structures and bioactivities of cyclic peptides derived therefrom. This work suggests that such constrained cyclic peptides can be used as scaffolds to create a range of novel protein-like supramolecular structures (e.g. cylinders, troughs, cones, multi-loop structures, helix bundles) that are comparable in size, shape and composition to bioactive surfaces of proteins. They may therefore represent interesting starting points for the design of novel artificial proteins and artificial enzymes. (C) 2002 Elsevier Science Inc. All rights reserved.

Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression

Objectives: To identify potential molecular genetic determinants of cardiovascular ischemic tolerance in wild-type and transgenic hearts overexpressing A(1) adenosine receptors (A(1)ARs). Methods: cDNA microarrays were used to explore expression of 1824 genes ill wild-type hearts and ischemia-tolerant mouse hearts overexpressing A(1)ARs. Results: Overexpression of A(1)ARs reduced post-ischemic contractile dysfunction, limited arrhythmogenesis, and reduced necrosis by similar to80% in hearts subjected to 30 min global ischemia 60 mill reperfusion. Cardioprotection was abrogated by acute A(1)AR antagonism, and only a small number (19) of genes were modified by A(1)AR overexpression in normoxic hearts. Ischemia-reperfusion significantly altered expression of 75 genes in wild-type hearts (14 induced, 61 down-regulated), including genes for metabolic enzymes, structural/motility proteins, cell signaling proteins, defense/growth proteins, and regulators of transcription and translation. A(1)AR overexpression reversed the majority of gene down-regulation whereas gene induction was generally unaltered. Additionally, genes involved in cell defence, signaling and gene expression were selectively modified by ischemia in transgenic hearts (33 induced, 10 down-regulated), possibly contributing to the protected phenotype. Real-time PCR verified changes in nine selected genes, revealing concordance with array data. Transcription of the A(1)AR gene was also modestly reduced post-ischemia, consistent with impaired functional sensitivity to A(1)AR stimulation Conclusions: Data are presented regarding the early post-ischemic gene profile of intact heart. Reduced A(1)AR transcription is observed which may contribute to poor outcome from ischemia. A(1)AR overexpression selectively modifies post-ischemic gene expression, potentially contributing to ischemic-tolerance. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.

The rearrangements of naphthyinitrenes: UV/Vis and IR spectra of azirines, cyclic ketenimines, and cyclic nitrile ylides

Ar matrix photolysis of 1- and 2-naphthyl azides 3 and 4 at 313 nm initially affords the singlet naphthyl nitrenes, (1)1 and (1)2. Relaxation to the corresponding lower energy, persistent triplet nitrenes (3)1 and (3)2 competes with cyclization to the azirines 15 and 18, which can also be formed photochemically from the triplet nitrenes. On prolonged irradiation, the azirines can be converted to the seven-membered cyclic ketenimines 10 and 13, respectively, as described earlier by Dunkin and Thomson. However, instead of the o-quinoid ketenimines 16 and 19, which are the expected primary ring-opening products of azirines 15 and 18, respectively, we observed their novel bond-shift isomers 17 and 20, which may be formally regarded as cyclic nitrile ylides. The existence of such ylidic heterocumulenes has been predicted previously, but this work provides the first experimental observation of such species. The factors which are responsible for the special stability of the ylidic species 17 and 20 are discussed.

The cyclic antimicrobial peptide RTD-1 induces stabilized lipid-peptide domains more efficiently than its open-chain analogue

The effects of a mammalian cyclic antimicrobial peptide, rhesus theta defensin 1 (RTD-1) and its open chain analogue (oRTD-1), on the phase behaviour and structure of model membrane systems (dipalmitoyl phosphatidylcholine, DPPC and dipalmitoyl phosphatidylglycerol, DPPG) were studied. The increased selectivity of RTD-1 for anionic DPPG over zwitterionic DPPC was shown by differential scanning calorimetry. RTD-1, at a molar peptide-lipid ratio of 1:100, induced considerable changes in the phase behaviour of DPPG, but not of DPPC. The main transition temperature, T-m, Was unchanged, but additional phase transitions appeared above T-m. oRTD-1 induced similar effects. However, the effects were not observable below a peptide:lipid molar ratio of 1:50, which correlates with the weaker biological activity of oRTD-1. Small-and wide-angle X-ray scattering revealed for DPPG the appearance of additional structural features induced by RTP-1 above T-m, which were interpreted as correlated lamellar structures, with increased order of the fatty acyl side chains of the lipid. It is proposed that after initial electrostatic interaction of the cationic rim of the peptide with the anionic DPPG headgroups, leading to stabilized lipid-peptide clusters, the hydrophobic face of the peptide assists in its interaction with the fatty acyl side chains eventually leading to membrane disruption. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: The importance of the cyclic cystine knot

The cyclotides constitute a recently discovered family of plant-derived peptides that have the unusual features of a head-to-tail cyclized backbone and a cystine knot core. These features are thought to contribute to their exceptional stability, as qualitatively observed during experiments aimed at sequencing and characterizing early members of the family. However, to date there has been no quantitative study of the thermal, chemical, or enzymatic stability of the cyclotides. In this study, we demonstrate the stability of the prototypic cyclotide kalata B1 to the chaotropic agents 6 M guanidine hydrochloride (GdHCl) and 8 M urea, to temperatures approaching boiling, to acid, and following incubation with a range of proteases, conditions under which most proteins readily unfold. NMR spectroscopy was used to demonstrate the thermal stability, while fluorescence and circular dichroism were used to monitor the chemical stability. Several variants of kalata B1 were also examined, including kalata 132, which has five amino acid substitutions from B1, two acyclic permutants in which the backbone was broken but the cystine knot was retained, and a two-disulfide bond mutant. Together, these allowed determinations of the relative roles of the cystine knot and the circular backbone on the stability of the cyclotides. Addition of a denaturant to kalata B1 or an acyclic permutant did not cause unfolding, but the two-disulfide derivative was less stable, despite having a similar three-dimensional structure. It appears that the cystine knot is more important than the circular backbone in the chemical stability of the cyclotides. Furthermore, the cystine knot of the cyclotides is more stable than those in similar-sized molecules, judging by a comparison with the conotoxin PVIIA. There was no evidence for enzymatic digestion of native kalata B1 as monitored by LC-MS, but the reduced form was susceptible to proteolysis by trypsin, endoproteinase Glu-C, and thermolysin. Fluorescence spectra of kalata B1 in the presence of dithiothreitol, a reducing agent, showed a marked increase in intensity thought to be due to removal of the quenching effect on the Trp residue by the neighboring Cys5-Cys17 disulfide bond. In general, the reduced peptides were significantly more susceptible to chemical or enzymatic breakdown than the oxidized species.