The molecular epidemiology of variant CJD

The emergence of the novel prion diseases bovine spongiform encephalopathy (BSE) and, subsequently, variant Creutzfeldt-Jakob disease (vCJD) in epidemic forms has attracted much scientific attention. The oral transmission of these disorders, the causative relationship of vCJD to BSE and the resistance of the transmissible agents in both disorders to conventional forms of decontamination has caused great public health concern. The size of the still emerging vCJD epidemic is thankfully much lower than some early published estimates. This paper reviews current knowledge of the factors that influence the development of vCJD: the properties of the infectious agent; the route of inoculation and individual susceptibility factors. The current epidemiological data are reviewed, along with relevant animal transmission studies. In terms of genetic susceptibility, the best characterised is the common single nucleotide polymorphism at codon 129 of prion protein gene. Current biomarkers and future areas of research will be discussed. These issues are important in informing precautionary measures and the ongoing monitoring of vCJD

Design and Synthesis of Hoogsteen-Binding Peptide Nucleic Acid Monomers with Extended Linkers for Triple Helical U-A Recognition in RNA

RNA provides many functions within biological systems. For example, noncoding RNA (ncRNA), a form of RNA that is not part of transcription or translation, serves a variety of unique roles, such as catalysis or gene regulation. ncRNA generally forms double helical motifs that are ripe for molecular recognition. Sequence selective recognition of double helical RNA (dhRNA) can be achieved using Peptide Nucleic Acids (PNA) through triple helical formation by Hoogsteen hydrogen bonding of PNA nucleobases in the major groove of dhRNA. However, strong, and selective recognition is typically limited to polypurine strands and pyrimidine recognition remains an unsolved problem. A promising solution uses extended nucleobases to reach across the Hoogsteen face of the RNA base pair, bypassing the pyrimidine, and binding with the distal purine. Using this strategy, we designed and synthesized new extended nucleobases to help uncover the ideal linker length and heterocyclic substitution for optimal molecular recognition

Editorial for "Diffusion Tensor Imaging for Quantitative Assessment of Anterior Cruciate Ligament Injury Grades and Graft".

Tears to the anterior cruciate ligament (ACL) are common and serious knee injuries which tend to occur in young, active individuals. They result in functional impairment and require a period of relative immobilisation followed by rehabilitation, often leading to surgery. Individuals suffering from an ACL injury also have a higher risk of developing osteoarthritis as a long-term consequence(1, 2). ACL reconstructive surgery using a tendon graft remains the clinical standard of care to provide stability to the knee joint and allow patients to return to sport quicker. However, the question of when to allow patients to return to high-level sport remains hotly debated, as the risk of sustaining a second ACL rupture following reconstructive surgery is highest within the subsequent two years(3). While conventional MRI methods continue to provide high diagnostic structural information for ACL injuries, they are unable to deliver advanced quantitative measures required for biological tissue characterisation and longitudinal observation of graft maturation. Promising techniques such as diffusion tensor imaging (DTI), are used for research purposes only and have not yet made the translation into routine clinical application.University of Cambridg

Bifurcations of discrete breathers in a diatomic Fermi-Pasta-Ulam chain

Discrete breathers are time-periodic, spatially localized solutions of the equations of motion for a system of classical degrees of freedom interacting on a lattice. Such solutions are investigated for a diatomic Fermi-Pasta-Ulam chain, i. e., a chain of alternate heavy and light masses coupled by anharmonic forces. For hard interaction potentials, discrete breathers in this model are known to exist either as ``optic breathers'' with frequencies above the optic band, or as ``acoustic breathers'' with frequencies in the gap between the acoustic and the optic band. In this paper, bifurcations between different types of discrete breathers are found numerically, with the mass ratio m and the breather frequency omega as bifurcation parameters. We identify a period tripling bifurcation around optic breathers, which leads to new breather solutions with frequencies in the gap, and a second local bifurcation around acoustic breathers. These results provide new breather solutions of the FPU system which interpolate between the classical acoustic and optic modes. The two bifurcation lines originate from a particular ``corner'' in parameter space (omega,m). As parameters lie near this corner, we prove by means of a center manifold reduction that small amplitude solutions can be described by a four-dimensional reversible map. This allows us to derive formally a continuum limit differential equation which characterizes at leading order the numerically observed bifurcations.Comment: 30 pages, 10 figure

Multi-site breathers in Klein-Gordon lattices: stability, resonances, and bifurcations

We prove the most general theorem about spectral stability of multi-site breathers in the discrete Klein-Gordon equation with a small coupling constant. In the anti-continuum limit, multi-site breathers represent excited oscillations at different sites of the lattice separated by a number of "holes" (sites at rest). The theorem describes how the stability or instability of a multi-site breather depends on the phase difference and distance between the excited oscillators. Previously, only multi-site breathers with adjacent excited sites were considered within the first-order perturbation theory. We show that the stability of multi-site breathers with one-site holes change for large-amplitude oscillations in soft nonlinear potentials. We also discover and study a symmetry-breaking (pitchfork) bifurcation of one-site and multi-site breathers in soft quartic potentials near the points of 1:3 resonance.Comment: 34 pages, 12 figure

A New Approach of Designing Superalloys for Low Density

New low-density single-crystal (LDS) alloy, have bee. developed for turbine blade applications, which have the potential for significant improvements in the thrust-to-weight ratio over current production superalloys. An innovative alloying strategy was wed to achieve alloy density reductions, high-temperature creep resistance, microstructural stability, and cyclic oxidation resistance. The alloy design relies on molybdenum as a potent. lower-density solid-solution strengthener in the nickel-based superalloy. Low alloy density was also achieved with modest rhenium levels tmd the absence of tungsten. Microstructural, physical mechanical, and environmental testing demonstrated the feasibility of this new LDS superalloy design

Low-Density, Creep-Resistant Single-Crystal Superalloys

Several recently formulated nickel-base superalloys have been developed with excellent high-temperature creep resistance, at lower densities than those of currently used nickel-base superalloys. These alloys are the latest products of a continuing effort to develop alloys that have even greater strength-to-weight ratios, suitable for use in turbine blades of aircraft engines. Mass densities of turbine blades exert a significant effect on the overall weight of aircraft. For a given aircraft, a reduction in the density of turbine blades enables design reductions in the weight of other parts throughout the turbine rotor, including the disk, hub, and shaft, as well as supporting structures in the engine. The resulting total reduction in weight can be 8 to 10 times that of the reduction in weight of the turbine blades. The approach followed in formulating these alloys involved several strategies for identifying key alloying elements and the range of concentration of each element to study. To minimize the number of alloys needed to be cast, a design-of--experiments methodology was adopted. A statistics-based computer program that models the effects of varying compositions of four elements, including effects of two-way interactions between elements, was used to test all possible alloys within the design space. The starting points for the computational analysis were three alloy compositions mandated by engineering consensus. After likewise identification of key alloying elements to vary and the allowed ranges of concentrations, the computer program then selects a minimum number of alloys within the design space to allow determination of effects for all four elements and their interactions