Optimization of flow diverters for cerebral aneurysms

A modern technique to treat cerebral aneurysms is to insert a flow diverter in the parent artery. In order to produce an optimal design of such devices, we consider a methodology combining simulated annealing optimization and lattice Boltzmann simulations. Our results surpass, in terms of stent efficiency, those obtained in the recent literature with an other optimization method. Although our approach is still in 2D, it demonstrates the potential of the method. We give some hint on how the 3D cases can be investigated.     

Total Synthesis and Biological Evaluation of the Antibiotic Lysocin E and Its Enantiomeric,Epimeric, and N‐Demethylated Analogues

Lysocin E, a macrocyclic peptide, exhibits potent antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA) through a novel mechanism. The first total synthesis of lysocin E was achieved by applying a full solid‐phase strategy. The developed approach also provides rapid access to the enantiomeric, epimeric, and N‐demethylated analogues of lysocin E. Significantly, the antibacterial activity of the unnatural enantiomer was comparable to that of the natural isomer, suggesting the absence of chiral recognition in its mode of action.     

Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide

By using dimethylformamide to suppress the O-to-N acyl migration, we efficiently synthesized an O-acyl isopeptide by native chemical ligation of a peptide-thioester and a Cys-O-acyl isopeptide. The reaction mixture was then loaded onto an octadecylsilane reverse-phase HPLC column, and the isopeptide was purified by using a linear gradient of CH₃CN in 0.1% aqueous trifluoroacetic acid. The recovery rate of the O-acyl isopeptide was considerably higher than that of the corresponding native polypeptide. Synthesis of O-acyl isopeptides via native chemical ligation, with O-to-N acyl migration as the final step to give the native form, has potential as an efficient method of constructing hydrophobic polypeptides.     

Conserved Tyr223(5.58) plays different roles in the activation and G-protein interaction of rhodopsin

Rhodopsin, a seven transmembrane helix (TM) receptor, binds its ligand 11-cis-retinal via a protonated Schiff base. Coupling to the G-protein transducin (G(t)) occurs after light-induced cis/trans-retinal isomerization, which leads through photoproducts into a sequence of metarhodopsin (Meta) states: Meta I ? Meta IIa ? Meta IIb ? Meta IIbH(+). The structural changes behind this three-step activation scheme are mediated by microswitch domains consisting of conserved amino acids. Here we focus on Tyr223(5.58) as part of the Y(5.58)X(7)K(R)(5.66) motif. Mutation to Ala, Phe, or Glu results in specific impairments of G(t)-activation measured by intrinsic G(t) fluorescence. UV-vis/FTIR spectroscopy of rhodopsin and its complex with a C-terminal G(t)α peptide allows the assignment of these deficiencies to specific steps in the activation path. Effects of mutation occur already in Meta I but do not directly influence deprotonation of the Schiff base during formation of Meta IIa. Absence of the whole phenol ring (Y223A) allows the activating motion of TM6 in Meta IIb but impairs the coupling to G(t). When only the hydroxyl group is lacking (Y223F), Meta IIb does not accumulate, but the activity toward G(t) remains substantial. From the FTIR features of Meta IIbH(+) we conclude that proton uptake to Glu134(3.49) is mandatory for Tyr223(5.58) to engage in the interaction with the key player Arg135(3.50) predicted by X-ray analysis. This polar interaction is partially recovered in Y223E, explaining its relatively high activity. Only the phenol side chain of tyrosine provides all characteristics for accumulation of the active state and G-protein activation.     

Light-induced conformational change and product release in DNA repair by (6-4) photolyase

Proteins of the cryptochrome/photolyase family share high sequence similarities, common folds, and the flavin adenine dinucleotide (FAD) cofactor, but exhibit diverse physiological functions. Mammalian cryptochromes are essential regulatory components of the 24 h circadian clock, whereas (6-4) photolyases recognize and repair UV-induced DNA damage by using light energy absorbed by FAD. Despite increasing knowledge about physiological functions from genetic analyses, the molecular mechanisms and conformational dynamics involved in clock signaling and DNA repair remain poorly understood. The (6-4) photolyase, which has strikingly high similarity to human clock cryptochromes, is a prototypic biological system to study conformational dynamics of cryptochrome/photolyase family proteins. The entire light-dependent DNA repair process for (6-4) photolyase can be reproduced in a simple in vitro system. To decipher pivotal reactions of the common FAD cofactor, we accomplished time-resolved measurements of radical formation, diffusion, and protein conformational changes during light-dependent repair by full-length (6-4) photolyase on DNA carrying a single UV-induced damage. The (6-4) photolyase by itself showed significant volume changes after blue-light activation, indicating protein conformational changes distant from the flavin cofactor. A drastic diffusion change was observed only in the presence of both (6-4) photolyase and damaged DNA, and not for (6-4) photolyase alone or with undamaged DNA. Thus, we propose that this diffusion change reflects the rapid (50 μs time constant) dissociation of the protein from the repaired DNA product. Conformational changes with such fast turnover would likely enable DNA repair photolyases to access the entire genome in cells.     

Total synthesis of polygalolide A

The total synthesis of polygalolide A was accomplished through intramolecular C-glycosylation of glucal modified with siloxyfuran. The siloxyfuran group and siloxy substituent at the C-3 position played crucial roles in allowing direct access to the highly substituted oxabicyclo[3.2.1] core skeleton with correct quaternary stereogenic centers.     

On homotopy groups of quandle spaces and the quandle homotopy invariant of links

For a quandle X, the quandle space BX is defined, modifying the rack space of Fenn, Rourke and Sanderson (1995) [13], and the quandle homotopy invariant of links is defined in Z[π₂(BX)], modifying the rack homotopy invariant of Fenn, Rourke and Sanderson (1995) [13]. It is known that the cocycle invariants introduced in Carter et al. (2005) [3], Carter et al. (2003) [5], Carter et al. (2001) [6] can be derived from the quandle homotopy invariant.In this paper, we show that, for a finite quandle X, π₂(BX) is finitely generated, and that, for a connected finite quandle X, π₂(BX) is finite. It follows that the space spanned by cocycle invariants for a finite quandle is finitely generated. Further, we calculate π₂(BX) for some concrete quandles. From the calculation, all cocycle invariants for those quandles are concretely presented. Moreover, we show formulas of the quandle homotopy invariant for connected sum of knots and for the mirror image of links.     

Unexpected electron transfer in cryptochrome identified by time-resolved EPR spectroscopy

Subtle differences in the local sequence and conformation of amino acids can result in diversity and specificity in electron transfer (ET) in proteins, despite structural conservation of the redox partners. For individual ET steps, distance is not necessarily the decisive parameter; orientation and solvent accessibility of the ET partners, and thus the stabilization of the charge-separated states, contribute substantially.     

Soluble magnesium and titanium catalyst components for ethylene polymerization

The catalyst system comprised of a heptane solution of magnesiumoctoate-H₂O-Tetrabutoxytitanium/diethylaluminumchloride was highly active for ethylene polymerization at a high temperature. High productivity for the catalyst system at a low temperature was achieved by the aging of the catalyst components. The effect of different orders of addition of the catalyst components on productivity was investigated to assume the role of each components in the formation of active species.