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Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adeno‐associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumor‐targeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumor‐bearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasome‐inhibiting drugs and AAVP should be considered for clinical anticancer therapy., Highlights ► Proteasome in cancer is a barrier to tumor targeting by RGD4C/AAVP.► Proteasome inhibiting drugs enhance targeted gene transfer by RGD4C/AAVP.► Proteasome inhibition increases targeted cancer gene therapy by RGD4C/AAVP.► RGD4C/AAVP persistence in cancer is improved by proteasome inhibition

Theoretical studies have predicted that scandium can bind to the twelve five-membered rings in C 60 . It is then possible to stabilize four dihydrogen ligands (H 2 ) on each Sc atom with a binding energy of ∼30 kJ/mol, ideal for vehicular hydrogen storage. The resulting C 60 [ScH 2 (H 2 ) 4 ] 12 complex is predicted to be a minimum energy structure with ∼7.0 wt% reversible hydrogen capacity. However, wet chemical synthesis of the calculated η 5 -coordinated fullerene complex is unprecedented. The chemistry of C 60 is generally olefinic (i.e., η 2 -coordination, in which the metal is coordinated to two carbon atoms contributing two electrons to the bonding). Furthermore, stabilization of multiple dihydrogen ligands on a single transition metal has not been demonstrated. Recently we have probed new synthesis techniques in order to coordinate C 60 with either Fe, Sc, Cr, Co or Li. The new compounds were characterized with solid-state nuclear magnetic resonance, and structures have been proposed. All of the structures were found to have unique binding sites for hydrogen employing the technique of temperature programmed desorption. Furthermore, some of the structures were shown to have significant hydrogen capacities with volumetric measurements.

We report on the fabrication and characterization of molecular junctions which are fabricated with electromigration and subsequent trapping of the molecule from solution. Transport measurements show molecule-specific features (vibrational modes; gate coupling) and indicate the presence of a single molecule in the gap. Electromigrated junctions can be very stable and allow for temperature dependent measurements, which provide, next to gate dependent measurements, an additional tool to perform detailed studies of transmolecular conduction mechanisms.

Emerging developments in geographic information systems and distributed computing offer a roadmap towards an unprecedented spatial data infrastructure in the climate sciences. Key to this are the standards developments for digital geographic information being led by the International Organisation for Standardisation (ISO) technical committee on geographic information/geomatics (TC211) and the Open Geospatial Consortium (OGC). These, coupled with the evolution of standardised web services for applications on the internet by the World Wide Web Consortium (W3C), mean that opportunities for both new applications and increased interoperability exist. These are exemplified by the ability to construct ISO-compliant data models that expose legacy data sources through OGC web services. This paper concentrates on the applicability of these standards to climate data by introducing some examples and outlining the challenges ahead. An abstract data model is developed, based on ISO standards, and applied to a range of climate data –both observational and modelled. An OGC Web Map Server interface is constructed for numerical weather prediction (NWP) data stored in legacy data files. A W3C web service for remotely accessing gridded climate data is illustrated. Challenges identified include the following: first, both the ISO and OGC specifications require extensions to support climate data. Secondly, OGC services need to fully comply with W3C web services, and support complex access control. Finally, to achieve real interoperability, broadly accepted community-based semantic data models are required across the range of climate data types. These challenges are being actively pursued, and broad data interoperability for the climate sciences appears within reach. Copyright © 2005 Royal Meteorological Society.

We provide a rapid and accurate method for calculating the prolate and oblate spheroidal wave functions (PSWFs and OSWFs), Smn(c; ), and their eigenvalues, mn, for arbitrary complex size parameter c in the asymptotic regime of large jcj, m and n fixed. The ability to calculate these SWFs for large and complex size parameters is important for many applications in mathematics, engineering, and physics. For arbitrary arg(c), the PSWFs and their eigenvalues are accurately expressed by established prolate-type or oblate-type asymptotic expansions. However, determining the proper expansion type is dependent upon finding spheroidal branch points, c mn ;r , in the complex c-plane where the PSWF alternates expansion type due to analytic continuation. We implement a numerical search method for tabulating these branch points as a function of spheroidal parameters m, n, and arg(c). The resulting table allows rapid determination of the appropriate asymptotic expansion type of the SWFs. Normalizations, which are dependent on c, are derived for both the prolate and oblate-type asymptotic expansions and for both (n m) even and odd. The ordering for these expansions is different from the original ordering of the SWFs and is dictated by the location of c mn ;r . We document this ordering for the specific case of arg(c) = =4 which occurs for the diffusion equation in spheroidal coordinates. Some representative values of mn and Smn(c; ) for large, complex c are also given.

In recent years, a number of curriculum reform projects have championed the notion of having students do science in ways that move beyond hands-on work with authentic materials and methods, or developing a conceptual grasp of current theories. These reformers have argued that students should come to an understanding of science through doing the discipline and taking a high degree of agency over investigations from start to finish. This stance has occasionally been mocked by its critics as an attempt to create “little scientists”—a mission, it is implied, that is either romantic or without purpose. Here, we make the strong case for a practice-based scientific literacy, arguing through three related empirical studies that taking the notion of “little scientists” seriously might be more productive in achieving current standards for scientific literacy than continuing to refine ideas and techniques based on the coverage of conceptual content. Study 1 is a classroom case study that illustrates how project-based instruction can be carried out when teachers develop guidance and support strategies to bootstrap students' participation in forms of inquiry they are still in the process of mastering. Study 2 shows how sustained on-line work with volunteer scientists appears to influence students' success in formulating credible scientific arguments in written project reports following an authentic genre. Study 3, using data from three suburban high school classes, suggests that involving students in the formulation of research questions and data analysis strategies results in better spontaneous use of empirical data collection and analysis strategies on a transfer task. The study also suggests that failing to involve students in the formulation of research can result in a loss of agency. The implications of these findings for future research and practice are discussed. © 2004 Wiley Periodicals, Inc. J Res Sci Teach 41: 234–266, 2004

The nm23 genes encode a family of multifunctional proteins with well-documented enzymatic and DNA-binding functions. There are five isoforms of nm23 of which two, nm23-H1 and nm23-H2 have been widely studied within the context of metastasis suppression in a large variety of human cancers. However, the role of nm23 in mediating the invasive behavior of central nervous system neoplasms remains to be clarified. In the present study, we provide evidence that nm23 may suppress the invasive phenotype in primary human brain tumors.

In recent years progress has been made in applying moving and deforming mesh systems to phase change problems. This allows the numerical attention where it is needed, near the migrating phase change zone. In spatially unbounded problems one hopes that numerically finite outer boundaries either escape significant activity or are automatically pushed further away as activity nears. Not infrequently this approach fails. Temperature activity often spreads more rapidly than phase change, thereby reaching far boundaries; stretching of the mesh by movement of far boundaries can challenge mesh control and cause ill-conditioning. In this paper the advantages of time dependent mesh adaption are enhanced by the joining of a new formulation for infinite elements to far boundaries. This is accomplished through a co-ordinate transformation within the framework of conventional 2-D quadratic, biquadratic, and linear–quadratic elements. Standard 2 by 2 Gauss–Legendre quadrature suffices throughout and normal Galerkin finite element features are undisturbed, including strict conservation of energy. The formulation is independent of global co-ordinates, entails no restrictions on the unknown function and should be applicable to other problem types. All test cases on quadrilateral and triangular grids show very significant improvements with infinite elements relative to comparable solution systems using strictly finite grids.

Two-dimensional heat conduction phase change problems are solved using a moving boundary-moving mesh approach. A transfinite mapping technique successfully controls interior mesh motion, and numerical results compare well with analytical solutions. Calculations also agree well with two-dimensional laboratory data for cases featuring time-dependent boundary conditions.

Boundary integral equation methods are presented for the solution of some two-dimensional phase change problems. Convection may enter through boundary conditions, but cannot be considered within phase boundaries. A general formulation based on space-time Green's functions is developed using the complete heat equation, followed by a simpler formulation using the Laplace equation. The latter is pursued and applied in detail. An elementary, noniterative system is constructed, featuring linear interpolation over elements on a polygonal boundary. Nodal values of the temperature gradient normal to a phase change boundary are produced directly in the numerical solution. The system performs well against basic analytical solutions, using these values in the interphase jump condition, with the simplest formulation of the surface normal at boundary vertices. Because the discretized surface changes automatically to fit the scale of the problem, the method appears to offer many of the advantages of moving mesh finite element methods. However, it only requires the manipulation of a surface mesh and solution for surface variables. In some applications, coarse meshes and very large time steps may be used, relative to those which would be required by fixed grid domain methods. Computations are also compared to original lab data, describing two-dimensional soil freezing with a time-dependent boundary condition. Agreement between simulated and measured histories is good.