Between history and values: A study on the nature of interpretation in international law

My thesis discusses the place of evaluative judgements in the interpretation of general international law. It concentrates on two questions. First, whether it is possible to interpret international legal practices without making an evaluative judgement about the point or value that provides the best justification of these practices. Second, whether the use of evaluative judgements in international legal interpretation threatens to undermine the objectivity of international law, the neutrality of international lawyers or the consensual and voluntary basis of the international legal system. I answer both questions in the negative. As regards the first, I argue that international legal practice has an interpretive structure, which combines appeals to the history of international practice with appeals to the principles and values that these practices are best understood as promoting. This interpretive structure is apparent not only in the claims of international lawyers about particular rules of international law (here I use the rule of estoppel as an example) but also in the most basic intuitions of international theorists about the theory and sources of general international law. I then argue that some popular concerns to the effect that the exercise of evaluation in the interpretation of international law will undermine the coherence or the usefulness of the discipline are generally unwarranted. The fact that international legal practice has an interpretive structure does not entail that propositions of international law are only subjectively true, that the interpreter enjoys license to manipulate their meaning for self-serving purposes, or that international law will collapse under the weight of irresolvable disagreements, divisions and conflicts about its proper interpretation

Potential for non-combustible nicotine products to reduce socioeconomic inequalities in smoking: a systematic review and synthesis of best available evidence

While some experts have emphasised the potential for e-cigarettes to facilitate cessation among smokers with low socioeconomic status (SES), there is limited evidence of their likely equity impact. We assessed the potential for electronic cigarettes and other non-combustible nicotine-containing products (NCNPs) to reduce inequalities in smoking by systematically reviewing evidence on their use by SES in countries at stage IV of the cigarette epidemic

Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine, a Nonribosomal Peptide Building Block.

A key problem in the engineering of pathways for the production of pharmaceutical compounds is the limited diversity of biosynthetic enzymes that restricts the attainability of suitable traits such as less harmful by-products, enhanced expression features or different cofactor requirements. A promising synthetic biology approach is to redesign the biosynthetic pathway by replacing the native enzymes by heterologous proteins from unrelated pathways. In this study, we applied this method to effectively re-engineer the biosynthesis of hydroxyphenylglycine (HPG), a building block for the calcium dependent antibiotic of Streptomyces coelicolor, a non-ribosomal peptide. A key step in HPG biosynthesis is the conversion of 4-hydroxymandelate to 4-hydroxyphenylglyoxylate, catalyzed by hydroxymandelate oxidase (HmO), with concomitant generation of H2O2. The same reaction can also be catalyzed by O2-independent mandelate dehydrogenase (MdlB), which is a catabolic enzyme involved in bacterial mandelate utilization. In this work, we engineered alternative HPG biosynthetic pathways by replacing the native HmO in S. coelicolor by both heterologous oxidases and MdlB dehydrogenases from various sources and confirmed the restoration of calcium-dependent antibiotic biosynthesis by biological and UHPLC-MS analysis. The alternative enzymes were isolated and kinetically characterized, confirming their divergent substrate specificities and catalytic mechanisms. These results demonstrate that heterologous enzymes with different physiological contexts can be used in a Streptomyces hosts to provide an expanded library of enzymatic reactions for a synthetic biology approach. This study thus broadens the options for the engineering of antibiotic production by using enzymes with different catalytic and structural features