Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons

The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration of transgene expression, which can be related to immune responses and to toxic effects of viral proteins. In addition, readministration is usually ineffective unless the animals are immunocompromised or a different adenovirus serotype is used. Recently, adenoviral vectors devoid of all viral coding sequences (helper-dependent or gutless vectors) have been developed to avoid expression of viral proteins. In mice, liver-directed gene transfer with AdSTK109, a helper-dependent adenoviral (Ad) vector containing the human α1-antitrypsin (hAAT) gene, resulted in sustained expression for longer than 10 months with negligible toxicity to the liver. In the present report, we have examined the duration of expression of AdSTK109 in the liver of baboons and compared it to first- generation vectors expressing hAAT. Transgene expression was limited to approximately 3-5 months with the first-generation vectors. In contrast, administration of AdSTK109 resulted in transgene expression for longer than a year in two of three baboons. We have also investigated the feasibility of circumventing the humoral response to the virus by sequential administration of vectors of different serotypes. We found that the ineffectiveness of readministration due to the humoral response to an Ad5 first-generation vector was overcome by use of an Ad2-based vector expressing hAAT. These data suggest that long-term expression of transgenes should be possible by combining the reduced immunogenicity and toxicity of helper-dependent vectors with sequential delivery of vectors of different serotypes

Performance issues in optical burst/packet switching

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-01524-3_8This chapter summarises the activities on optical packet switching (OPS) and optical burst switching (OBS) carried out by the COST 291 partners in the last 4 years. It consists of an introduction, five sections with contributions on five different specific topics, and a final section dedicated to the conclusions. Each section contains an introductive state-of-the-art description of the specific topic and at least one contribution on that topic. The conclusions give some points on the current situation of the OPS/OBS paradigms

Do Parental Licensing Schemes Violate the Rights of Biological Parents?

In his inventive and wide-ranging book, The Right to Be Loved, S. Matthew Liao develops a novel argument against licensing biological parents. Licensing schemes require prospective parents to demonstrate that they have the characteristics and means required for parenting. When would-be parents are found wanting, they are either not allowed to raise children, or have their authority restricted in a way that isn’t true of parents who pass the test. Liao believes that licensing biological parents (but not adoptive ones) can be rejected on principled grounds, without consideration of the effects expected from particular licensing schemes. This novel criticism differs from existing anti-licensing arguments, which tend to reject licensing schemes because of their effects

Exploiting disadvantage as causing harm

In Responding to Global Poverty, Christian Barry and Gerhard Øverland argue that, while exploitation is morally problematic, responsibilities not to exploit are characteristically less stringent than responsibilities not to harm. They even suggest that exploiters’ responsibilities to assist the exploited may be weaker than the responsibilities of culpable bystanders who are able to help the poor but fail to do so We think Barry and Øverland underestimate the prospects of the exploitation argument. In our paper, we suggest that exploitation can plausibly be understood as a kind of harm. If exploitation harms, then it requires special justification and can generate stringent responsibilities not to exploit that have a different ground than those generated by morally culpable failures to assist. This suggests an important way to rehabilitate arguments for poverty relief on the basis of a duty not to harm, and that there is more interesting territory to explore than Barry and Øverland’s arguments suggest