Progress in the use of adeno-associated viral vectors for gene therapy

The development of safe and efficient gene transfer vectors is crucial for the success of gene therapy trials. A viral vector system promising to meet these requirements is based on the apathogenic adeno-associated virus (AAV-2), a member of the parvovirus family. The advantages of this vector system is the stability of the viral capsid, the low immunogenicity, the ability to transduce both dividing and non-dividing cells, the potential to integrate site specifically and to achieve long-term gene expression even in vivo, and its broad tropism allowing the efficient transduction of diverse organs including the skin. All this makes AAV-2 attractive and efficient for in vitro gene transfer and local injection in vivo. This review covers the progress made in AAV vector technology including the development of AAV vectors based on other serotypes, summarizes the results obtained by AAV targeting vectors and outlines potential applications in the field of cutaneous gene therapy. Copyright (C) 2004 S. Karger AG, Basel

Viscous computation of a space shuttle flow field

A procedure is presented, as well as some results, to calculate the flow over the winged orbiter. This necessitates the use of two computer codes. A parabolized marching Navier-Stokes code is used to obtain the solution up to the bow shock-wing shock interaction region and for the region after the interaction. An unsteady Navier-Stokes code is to be used in the region of the shock interaction. Only resuls for the marching code are presented. For the flow conditions calculated, M infinity = 7.9, alpha = 25 deg, T(wall) = 540 R, Re(L) = 60728 per inch, laminar or turbulent, the PNS code was marched up to an X/L = 0.7 which is where the bow shock-wing shock interaction region occurs

User's Manual for FOMOCO Utilities-Force and Moment Computation Tools for Overset Grids

In the numerical computations of flows around complex configurations, accurate calculations of force and moment coefficients for aerodynamic surfaces are required. When overset grid methods are used, the surfaces on which force and moment coefficients are sought typically consist of a collection of overlapping surface grids. Direct integration of flow quantities on the overlapping grids would result in the overlapped regions being counted more than once. The FOMOCO Utilities is a software package for computing flow coefficients (force, moment, and mass flow rate) on a collection of overset surfaces with accurate accounting of the overlapped zones. FOMOCO Utilities can be used in stand-alone mode or in conjunction with the Chimera overset grid compressible Navier-Stokes flow solver OVERFLOW. The software package consists of two modules corresponding to a two-step procedure: (1) hybrid surface grid generation (MIXSUR module), and (2) flow quantities integration (OVERINT module). Instructions on how to use this software package are described in this user's manual. Equations used in the flow coefficients calculation are given in Appendix A

Grid Sensitivity Study for Slat Noise Simulations

The slat noise from the 30P/30N high-lift system is being investigated through computational fluid dynamics simulations in conjunction with a Ffowcs Williams-Hawkings acoustics solver. Many previous simulations have been performed for the configuration, and the case was introduced as a new category for the Second AIAA workshop on Benchmark problems for Airframe Noise Configurations (BANC-II). However, the cost of the simulations has restricted the study of grid resolution effects to a baseline grid and coarser meshes. In the present study, two different approaches are being used to investigate the effect of finer resolution of near-field unsteady structures. First, a standard grid refinement by a factor of two is used, and the calculations are performed by using the same CFL3D solver employed in the majority of the previous simulations. Second, the OVERFLOW code is applied to the baseline grid, but with a 5th-order upwind spatial discretization as compared with the second-order discretization used in the CFL3D simulations. In general, the fine grid CFL3D simulation and OVERFLOW calculation are in very good agreement and exhibit the lowest levels of both surface pressure fluctuations and radiated noise. Although the smaller scales resolved by these simulations increase the velocity fluctuation levels, they appear to mitigate the influence of the larger scales on the surface pressure. These new simulations are used to investigate the influence of the grid on unsteady high-lift simulations and to gain a better understanding of the physics responsible for the noise generation and radiation

User's manual for the HYPGEN hyperbolic grid generator and the HGUI graphical user interface

The HYPGEN program is used to generate a 3-D volume grid over a user-supplied single-block surface grid. This is accomplished by solving the 3-D hyperbolic grid generation equations consisting of two orthogonality relations and one cell volume constraint. In this user manual, the required input files and parameters and output files are described. Guidelines on how to select the input parameters are given. Illustrated examples are provided showing a variety of topologies and geometries that can be treated. HYPGEN can be used in stand-alone mode as a batch program or it can be called from within a graphical user interface HGUI that runs on Silicon Graphics workstations. This user manual provides a description of the menus, buttons, sliders, and typein fields in HGUI for users to enter the parameters needed to run HYPGEN. Instructions are given on how to configure the interface to allow HYPGEN to run either locally or on a faster remote machine through the use of shell scripts on UNIX operating systems. The volume grid generated is copied back to the local machine for visualization using a built-in hook to PLOT3D

High-Lift Propeller Noise Prediction for a Distributed Electric Propulsion Flight Demonstrator

Over the past several years, the use of electric propulsion technologies within aircraft design has received increased attention. The characteristics of electric propulsion systems open up new areas of the aircraft design space, such as the use of distributed electric propulsion (DEP). In this approach, electric motors are placed in many different locations to achieve increased efficiency through integration of the propulsion system with the airframe. Under a project called Scalable Convergent Electric Propulsion Technology Operations Research (SCEPTOR), NASA is designing a flight demonstrator aircraft that employs many "high-lift propellers" distributed upstream of the wing leading edge and two cruise propellers (one at each wingtip). As the high-lift propellers are operational at low flight speeds (take-off/approach flight conditions), the impact of the DEP configuration on the aircraft noise signature is also an important design consideration. This paper describes efforts toward the development of a mulit-fidelity aerodynamic and acoustic methodology for DEP high-lift propeller aeroacoustic modeling. Specifically, the PAS, OVERFLOW 2, and FUN3D codes are used to predict the aerodynamic performance of a baseline high-lift propeller blade set. Blade surface pressure results from the aerodynamic predictions are then used with PSU-WOPWOP and the F1A module of the NASA second generation Aircraft NOise Prediction Program to predict the isolated high-lift propeller noise source. Comparisons of predictions indicate that general trends related to angle of attack effects at the blade passage frequency are captured well with the various codes. Results for higher harmonics of the blade passage frequency appear consistent for the CFD based methods. Conversely, evidence of the need for a study of the effects of increased azimuthal grid resolution on the PAS based results is indicated and will be pursued in future work. Overall, the results indicate that the computational approach is acceptable for fundamental assessment of low-noise high-lift propeller designs. The extent to which the various approaches may be used in a complementary manner will be further established as measured data becomes available for validation. Ultimately, it is anticipated that this combined approach may be used to provide realistic incident source fields for acoustic shielding/scattering studies on various aircraft configurations

Flipping the classroom:an effective approach to deal with diversity at higher education

Even though the flipped classroom is an increasingly popular method in education, a literature search shows a gap in research on this method in higher education. This article describes an experiment with two central questions: (1) How do students and lecturers assess the effectiveness of the FC method? And (2) What are crucial design elements? To be able to answer these questions we designed an experiment within a large-size, interdisciplinary, course. For three years we carefully monitored and evaluated the course. A mixed-method approach was used to collect data. Our findings show a positive contribution of the FC approach to the learning experience of students. We also found that a strong link between theory and practice is essential in the course design; combined with active learning we were able to involve students and stimulate them to reach a deeper level of understanding. Moreover, we believe that the FC approach offers opportunities to have a large interdisciplinary group, with different learning needs, work together on higher attainment levels

Chimera Grid Tools

Chimera Grid Tools (CGT) is a software package for performing computational fluid dynamics (CFD) analysis utilizing the Chimera-overset-grid method. For modeling flows with viscosity about geometrically complex bodies in relative motion, the Chimera-overset-grid method is among the most computationally cost-effective methods for obtaining accurate aerodynamic results. CGT contains a large collection of tools for generating overset grids, preparing inputs for computer programs that solve equations of flow on the grids, and post-processing of flow-solution data. The tools in CGT include grid editing tools, surface-grid-generation tools, volume-grid-generation tools, utility scripts, configuration scripts, and tools for post-processing (including generation of animated images of flows and calculating forces and moments exerted on affected bodies). One of the tools, denoted OVERGRID, is a graphical user interface (GUI) that serves to visualize the grids and flow solutions and provides central access to many other tools. The GUI facilitates the generation of grids for a new flow-field configuration. Scripts that follow the grid generation process can then be constructed to mostly automate grid generation for similar configurations. CGT is designed for use in conjunction with a computer-aided-design program that provides the geometry description of the bodies, and a flow-solver program

On QBF Proofs and Preprocessing

QBFs (quantified boolean formulas), which are a superset of propositional formulas, provide a canonical representation for PSPACE problems. To overcome the inherent complexity of QBF, significant effort has been invested in developing QBF solvers as well as the underlying proof systems. At the same time, formula preprocessing is crucial for the application of QBF solvers. This paper focuses on a missing link in currently-available technology: How to obtain a certificate (e.g. proof) for a formula that had been preprocessed before it was given to a solver? The paper targets a suite of commonly-used preprocessing techniques and shows how to reconstruct certificates for them. On the negative side, the paper discusses certain limitations of the currently-used proof systems in the light of preprocessing. The presented techniques were implemented and evaluated in the state-of-the-art QBF preprocessor bloqqer.Comment: LPAR 201

Multi-functional annular fairing for coupling launch abort motor to space vehicle

An annular fairing having aerodynamic, thermal, structural and acoustic attributes couples a launch abort motor to a space vehicle having a payload of concern mounted on top of a rocket propulsion system. A first end of the annular fairing is fixedly attached to the launch abort motor while a second end of the annular fairing is attached in a releasable fashion to an aft region of the payload. The annular fairing increases in diameter between its first and second ends