Plasma Photocathodes

Plasma wakefield accelerators offer accelerating and focusing electric fields three to four orders of magnitude larger than state-of-the-art radiofrequency cavity-based accelerators. Plasma photocathodes can release ultracold electron populations within such plasma waves and thus open a path toward tunable production of well-defined, compact electron beams with normalized emittance and brightness many orders of magnitude better than state-of-the-art. Such beams will have far-reaching impact for applications such as light sources, but also open up new vistas on high energy and high field physics. This paper reviews the innovation of plasma photocathodes, and reports on the experimental progress, challenges, and future prospects of the approach. Details of the proof-of-concept demonstration of a plasma photocathode in 90° geometry at SLAC FACET within the E-210: Trojan Horse program are described. Using this experience, alongside theoretical and simulation-supported advances, an outlook is given on future realizations of plasma photocathodes such as the upcoming E-310: Trojan Horse-II program at FACET-II with prospects toward excellent witness beam parameter quality, tunability, and stability. Future installations of plasma photocathodes also at compact, hybrid plasma wakefield accelerators, will then boost capacities and open up novel capabilities for experiments at the forefront of interaction of high brightness electron and photon beams.     

Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors

Carbon nanotubes (CNTs) constitute a class of nanomaterials that possess characteristics suitable for a variety of possible applications. Their compatibility with aqueous environments has been made possible by the chemical functionalization of their surface, allowing for exploration of their interactions with biological components including mammalian cells. Functionalized CNTs (f-CNTs) are being intensively explored in advanced biotechnological applications ranging from molecular biosensors to cellular growth substrates. We have been exploring the potential of f-CNTs as delivery vehicles of biologically active molecules in view of possible biomedical applications, including vaccination and gene delivery. Recently we reported the capability of ammonium-functionalized single-walled CNTs to penetrate human and murine cells and facilitate the delivery of plasmid DNA leading to expression of marker genes. To optimize f-CNTs as gene delivery vehicles, it is essential to characterize their interactions with DNA. In the present report, we study the interactions of three types of f-CNTs, ammonium-functionalized single-walled and multiwalled carbon nanotubes (SWNT-NH3+; MWNT-NH3+), and lysine-functionalized single-walled carbon nanotubes (SWNT-Lys-NH3+), with plasmid DNA. Nanotube-DNA complexes were analyzed by scanning electron microscopy, surface plasmon resonance, PicoGreen dye exclusion, and agarose gel shift assay. The results indicate that all three types of cationic carbon nanotubes are able to condense DNA to varying degrees, indicating that both nanotube surface area and charge density are critical parameters that determine the interaction and electrostatic complex formation between f-CNTs with DNA. All three different f-CNT types in this study exhibited upregulation of marker gene expression over naked DNA using a mammalian (human) cell line. Differences in the levels of gene expression were correlated with the structural and biophysical data obtained for the f-CNT:DNA complexes to suggest that large surface area leading to very efficient DNA condensation is not necessary for effective gene transfer. However, it will require further investigation to determine whether the degree of binding and tight association between DNA and nanotubes is a desirable trait to increase gene expression efficiency in vitro or in vivo. This study constitutes the first thorough investigation into the physicochemical interactions between cationic functionalized carbon nanotubes and DNA toward construction of carbon nanotube-based gene transfer vector systems.     

Oxidase‐Like Activity of Polymer‐Coated Cerium Oxide Nanoparticles

Inorganic enzyme? Ceria nanoparticles exhibit unique oxidase‐like activity at acidic pH values. These redox catalysts can be used in immunoassays (ELISA) when modified with targeting ligands (see picture; light blue and yellow structures are nanoparticles with attached ligands). This modification allows both for binding and for detection by the catalytic oxidation of sensitive colorimetric dyes (e.g. TMB).

     

Rapid genotyping of CYP2D6, CYP2C19 and TPMT polymorphisms by primer extension reaction in a dipstick format

In recent years an increasing amount of interest has been directed at the study and routine testing of polymorphisms responsible for variations in drug metabolism. Most of the current methods involve either time-consuming electrophoresis steps or specialized and expensive equipment. In this context, we have developed a rapid, simple and robust method for genotyping of CYP2D6*3, CYP2D6*4, CYP2C19*2, CYP2C19*3 and TPMT*2 single nucleotide polymorphisms (SNP). Genomic DNA is isolated from whole blood and the segments that span the SNP of interest are amplified by PCR. The products are subjected directly (without purification) to two primer extension (PEXT) reactions (three cycles each) using normal and mutant primers in the presence of biotin-dUTP. The PEXT primers contain a (dA)₃₀ segment at the 5′ end. The PEXT products are detected visually by a dry-reagent dipstick-type assay in which the biotinylated extension products are captured from immobilized streptavidin on the test zone of the strip and detected by hybridization with oligo(dT)-functionalized gold nanoparticles. Patient samples (76 variants in total) were genotyped and the results were fully concordant with those obtained by direct DNA sequencing.     

Biomedical applications of functionalised carbon nanotubes

The organic functionalisation of carbon nanotubes can improve substantially their solubility and biocompatibility profile; as a consequence, their manipulation and integration into biological systems has become possible so that functionalised carbon nanotubes hold currently strong promise as novel systems for the delivery of drugs, antigens and genes.     

Topological mixing in -spaces

If is a proper -space and a non-elementary discrete group of isometries acting properly discontinuously on it is shown that the geodesic flow on the quotient space is topologically mixing, provided that the generalized Busemann function has zeros on the boundary and the non-wandering set of the flow equals the whole quotient space of geodesics (the latter being redundant when is compact). Applications include the proof of topological mixing for (A) compact negatively curved polyhedra, (B) compact quotients of proper geodesically complete -spaces by a one-ended group of isometries and (C) finite -dimensional ideal polyhedra.

     

Galerkin and Runge–Kutta methods: unified formulation,a posteriori error estimates and nodal superconvergence

We unify the formulation and analysis of Galerkin and Runge–Kutta methods for the time discretization of parabolic equations. This, together with the concept of reconstruction of the approximate solutions, allows us to establish a posteriori superconvergence estimates for the error at the nodes for all methods.     

Optimal order a posteriori error estimates for a class of Runge–Kutta and Galerkin methods

We derive a posteriori error estimates, which exhibit optimal global order, for a class of time stepping methods of any order that include Runge–Kutta Collocation (RK-C) methods and the continuous Galerkin (cG) method for linear and nonlinear stiff ODEs and parabolic PDEs. The key ingredients in deriving these bounds are appropriate one-degree higher continuous reconstructions of the approximate solutions and pointwise error representations. The reconstructions are based on rather general orthogonality properties and lead to upper and lower bounds for the error regardless of the time-step; they do not hinge on asymptotics.     

Interior a posteriori error estimates for time discrete approximations of parabolic problems

We derive a posteriori estimates for single-step methods, including Runge–Kutta and Galerkin methods for the time discretization of linear parabolic equations. We focus on the estimation of the error at the nodes and derive a posteriori estimates that show the full classical order (superconvergence order) in the interior of the spatial domain without any compatibility assumptions.