Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Mobility management support and performance analysis for wireless MPLS networks

Multi‐Protocol Label Switching (MPLS) is deployed in the Internet backbone to support service differentiation and traffic engineering. In recent years, there has been interest in extending the MPLS capability to wireless access networks for mobility management support. In this paper, we present analysis of Micro Mobile MPLS, a new micro‐mobility management scheme which integrates the Mobile IP and MPLS protocols by using two‐level hierarchy architecture. Our proposal supports two protocol variants. First, the fast handoff process, which anticipates the LSP procedure set‐up with neighboring locations where a mobile node (MN) may move to, is provided to reduce service disruption. Second, a new mechanism based on the forwarding chain concept is proposed to track efficiently the host mobility within a domain. This concept can significantly reduce registration update costs and provide low handoff latency. Analytical models are developed and simulations are conducted to justify the benefits of our proposed mechanisms. Copyright © 2006 John Wiley & Sons, Ltd.     

Antimicrobial activity on the copolymers of 2,4‐dichlorophenyl methacrylate with methyl methacrylate: Synthesis and characterization

Copolymers of monomers 2,4‐dichlorophenyl methacrylate (2,4‐DMA) and methyl methacrylate (MMA) were synthesized with different monomer feed ratios using toluene as a solvent and 2,2′‐azobisisobutyronitrile (AIBN) as an initiator at 70 °C. The copolymers were characterized by IR‐spectroscopy, and copolymer composition was determined with UV‐spectroscopy. The linearization method of Fineman–Ross was employed to obtain the monomer reactivity ratios. The molecular weights and polydispersity indexes were determined by gel permeation chromatography (GPC). Thermogravimetric analyses of polymers were carried out in nitrogen atmosphere. The homo‐ and copolymers were tested for their antimicrobial properties against selected microorganisms. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5227–5234, 2004     

Equivalence of two linear programming relaxations for broadcast scheduling

A server needs to compute a broadcast schedule for n pages whose request times are known in advance. Outputting a page satisfies all outstanding requests for the page. The goal is to minimize the average waiting time of a client. In this paper, we show the equivalence of two apparently different relaxations that have been considered for this problem.     

Bilevel programming approach applied to the flow shop scheduling problem under fuzziness

This paper presents a fuzzy bilevel programming approach to solve the flow shop scheduling problem. The problem considered here differs from the standard form in that operators are assigned to the machines and imposing a hierarchy of two decision makers with fuzzy processing times. The shop owner considered higher level and assigns the jobs to the machines in order to minimize the flow time while the customer is the lower level and decides on a job schedule in order to minimize the makespan. In this paper, we use the concepts of tolerance membership function at each level to define a fuzzy decision model for generating optimal (satisfactory) solution for bilevel flow shop scheduling problem. A solution algorithm for solving this problem is given. Mathematics Subject Classification: 90C70, 90B36, 90C99     

Iterative methods and high-order difference schemes for 2D elliptic problems with mixed derivative

We derive a fourth-order compact finite difference scheme for a two-dimensional elliptic problem with a mixed derivative and constant coefficients. We conduct experimental study on numerical solution of the problem discretized by the present compact scheme and the traditional second-order central difference scheme. We study the computed accuracy achieved by each scheme and the performance of the Gauss-Seidel iterative method, the preconditioned GMRES iterative method, and the multigrid method, for solving linear systems arising from the difference schemes.     

Band bending at the Si(1 1 1)–SiO2 interface induced by low-energy ion bombardment

Experiments employing photoreflectance spectroscopy have uncovered band bending due to electrically active defects at the Si(1 1 1)–SiO₂ interface after sub-keV Ar⁺ ion bombardment. The band bending of about 0.5 eV resembles that for Si(1 0 0)–SiO₂, and both interfaces exhibit two kinetic regimes for the evolution of band bending upon annealing due to defects healing. The healing takes place about an order of magnitude more quickly at the (1 1 1) interface, however, probably because of less fully saturated bonding and higher compressive stress.     

Constructing ‘hair’ for the three charge hole

It has been found that the states of the 2-charge extremal D1–D5 system are given by smooth geometries that have no singularity and no horizon individually, but a ‘horizon’ does arise after ‘coarse-graining’. To see how this concept extends to the 3-charge extremal system, we construct a perturbation on the D1–D5 geometry that carries one unit of momentum charge P. The perturbation is found to be regular everywhere and normalizable, so we conclude that at least this state of the 3-charge system behaves like the 2-charge states. The solution is constructed by matching (to several orders) solutions in the inner and outer regions of the geometry. We conjecture the general form of ‘hair’ expected for the 3-charge system, and the nature of the interior of black holes in general.     

Diastereoselective Photochemical Synthesis of α-Amino-β-hydroxyketones by Photocycloaddition of Carbonyl Compounds to 2,5-Dimethyl-4-isobutyloxazole

Summary. The photocycloaddition of aldehydes and α-ketoesters to 2,5-dimethyl-4-isobutyloxazole leads to bicyclic oxetanes with high to moderate (exo) diastereoselectivity that can be easily ring-opened to give α-amino-β-hydroxyketones.