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

Cartesian Off-Body Grid Adaption for Viscous Time- Accurate Flow Simulation

An improved solution adaption capability has been implemented in the OVERFLOW overset grid CFD code. Building on the Cartesian off-body approach inherent in OVERFLOW and the original adaptive refinement method developed by Meakin, the new scheme provides for automated creation of multiple levels of finer Cartesian grids. Refinement can be based on the undivided second-difference of the flow solution variables, or on a specific flow quantity such as vorticity. Coupled with load-balancing and an inmemory solution interpolation procedure, the adaption process provides very good performance for time-accurate simulations on parallel compute platforms. A method of using refined, thin body-fitted grids combined with adaption in the off-body grids is presented, which maximizes the part of the domain subject to adaption. Two- and three-dimensional examples are used to illustrate the effectiveness and performance of the adaption scheme

Multihydroxy-functional oligophenylene oxide

Multihydroxy-functional oligophenylene oxide obtainable by reacting a compound containing hydroxyaryl comprising at least three hydroxyaryl groups according to formula (I), wherein R = an aromatic, aliphatic or cycloaliphatic group containing 1-50 carbon atoms, R, R = H or an aromatic, aliphatic or cycloaliphatic group containing 1-50 carbon atoms, or two of the R, R or R groups together constitute a ring structure containing 4-50 carbon atoms with a polyphenylene oxide in the presence of a catalyst complex comprising a transition metal and and amine

Functional oligomers, telechelics, graft- and star-shaped poly(2,6-dimethyl-1,4-phenylene ether)s prepared by redistribution

No abstract

Denken over dieren : dier en ding, zegen en zorg

Dit rapport, dat in opdracht van het ministerie van Economische zaken, Landbouw en Innovatie is opgesteld, beschrijft een eerste trendanalyse (nulmeting) van (verwachte) morele opvattingen in Nederland over de omgang met dieren, nu en in de toekomst ten behoeve van het dierbeleid. In dit onderzoek is gestreefd naar de volgende inzichten: 1) de hedendaagse publieke opvattingen over de omgang met dieren; 2) de thema's die in de verschillende dierpraktijken spelen; 3) de verwachte ontwikkeling van deze thema's in de komende 20 jaar

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

Predictors of outcome for severely emotionally disturbed children in treatment

Despite general agreement that severely emotionally disturbed children and adolescents are an "at risk" group, and that ongoing evaluation and research into the effectiveness of services provided for them is important, very little outcome evaluation actually takes place. The absence of well-conducted and appropriately interpreted studies is particularly notable for day or residential treatment programs, which cater for the most severely emotionally disturbed youths. This thesis outlines the main areas of conceptual, pragmatic and methodological confusion and neglect which impede progress in research in this area. It argues for plurality of data analytic strategies and research designs. It then critically reviews the reported findings about the effectiveness of day and residential treatment in specialist facilities, and the predictors of good outcomes for this treatment type. This review confirms that there is very little to guide practice. Having argued for the legitimacy of its methods and the necessity to address basic questions, the thesis reports the results of a naturalistic study based on data accumulated during a decade-long evaluative research program taking place at Arndell Child and Adolescent Unit, Sydney. The study addresses the question of what child, family and treatment variables predict outcome for 159 children and adolescents treated at this facility from 1990 to 1999. Statistically significant results with large effect size were obtained. Among the most disturbed subgroup of forty three children, (a) psychodynamic milieu-based treatment was shown to be more effective than the “empirically-validated” cognitive-behavioural treatment which superseded it in 1996, and (b) children from step-families showed better outcome than those from other family structures. Furthermore, it was found for the study sample as a whole that severe school-based problem behaviours were associated with a limited trajectory of improvement in home-based problem behaviour. These results are discussed with regard to implications for treatment, research methodology, policy and further studies

Flow characterisation for a validation study in high-speed aerodynamics

Validation studies are becoming increasingly relevant when investigating complex flow problems in high-speed aerodynamics. These investigations require calibration of numerical models with accurate data from the physical wind tunnel being studied. This paper presents the characterisation process for a joint experimental-computational study to investigate the streamwise corners of a Mach 2.5 channel flow. As well as checks of flow quality typically performed for phenomenological investigations, additional quantitative tests are conducted. The extra care to obtain high quality data and eliminate any systematic errors reveal useful information about the wind tunnel flow. Further important physical insights are gained from designing and conducting wind tunnel tests in conjunction with numerical simulations. Crucially, the close experimental-computational collaboration enabled the identification of secondary flows in the sidewall boundary-layers; these strongly influence the flow in the corner regions, the target of the validation study

A surface-patterned chip as a strong source of ultracold atoms for quantum technologies

Laser-cooled atoms are central to modern precision measurements. They are also increasingly important as an enabling technology for experimental cavity quantum electrodynamics, quantum information processing and matter–wave interferometry. Although significant progress has been made in miniaturizing atomic metrological devices, these are limited in accuracy by their use of hot atomic ensembles and buffer gases. Advances have also been made in producing portable apparatus that benefits from the advantages of atoms in the microkelvin regime. However, simplifying atomic cooling and loading using microfabrication technology has proved difficult. In this Letter we address this problem, realizing an atom chip that enables the integration of laser cooling and trapping into a compact apparatus. Our source delivers ten thousand times more atoms than previous magneto-optical traps with microfabricated optics and, for the first time, can reach sub-Doppler temperatures. Moreover, the same chip design offers a simple way to form stable optical lattices. These features, combined with simplicity of fabrication and ease of operation, make these new traps a key advance in the development of cold-atom technology for high-accuracy, portable measurement devices