Oxfam

Abstract Antisense oligonucleotides (ASOs) are a powerful class of drugs with the potential to treat a wide range of human diseases. However, the prediction of ASO efficacy remains challenging, as large-scale and costly experimental screens are typically required to identify optimal candidates for a specific therapeutic target. To address this challenge, we compiled ASO Atlas, a database comprising 188,521 RNase H-mediated ASO sequences targeting 334 unique genes with corresponding knockdown efficacy measurements extracted from published patents. Using ASO Atlas, we trained OligoAI, a deep learning model capable of jointly modelling RNA target context, ASO sequence, sugar and backbone chemistries, and dosage to predict in vitro efficacy. We experimentally validated OligoAI by targeting KCNT2, achieving a 5.72-fold reduction in screening effort compared to random selection. ASO Atlas provides the first systematic resource to rigorously evaluate hypotheses regarding key parameters in ASO design, including sequence composition, chemical modifications, and target region selection. Both ASO Atlas and OligoAI have been made freely accessible through an online web-tool with the aim of facilitating the accelerated optimisation of ASO design.

LCA is increasingly applied to the electromobility sector, in academic and industrial literature, and in policies. While there is awareness on the existence of specific gaps and lack of harmonization in LCA of electromobility, there is however still no common understanding on these and on their relevance. This study intends to develop this common understanding and to further explore potential ways forward. The analysis of gaps and lack of harmonization starts from, and expands the analysis of, the extensive review of state-of-the-art academic and industrial literature, and of existing guidelines and standards, performed by Eltohamy et al. (2024). It further builds on four additional actions: (i) review of position papers; (ii) workshops, gathering LCA experts from industry and research; (iii) in-depth survey on the LCA practice of selected industrials; and (iv) iterative, document-based, approach towards common identification and analysis of gaps. This study accordingly compiles and analyzes the gaps and lack of harmonization in LCA of the electromobility sector per LCA phase. It discusses how these limits alter LCA accuracy, comparability and comprehensiveness and their associated relevance as function of the study context. The identified gaps and lack of harmonization relate to (i) the LCA general method, and more specific rules regarding functional unit, approach to address multi-functionality, system boundaries, electricity modelling, normalization and weighting, sensitivity and uncertainty analysis, etc.; (ii) models used to support LCA, sometimes not accurately representing the real world (e.g. models for data gap filling, prospective EoL modelling, impact characterization); (iii) data, both in terms of (incomplete and imprecise) secondary datasets and of lack of primary data; and (iv) difficulties in implementation. The path forward to overcome these limitations is expected to rely firstly on research and development, particularly crucial to address actual gaps in models and data, and secondly on guidelines setting and consensus building, both key regarding harmonization of method-related issues. This study highlights, classifies and analyzes the existing gaps and lack of harmonization in LCA of the electromobility sector. It flags the key challenges and opportunities to be overcome in the path forward, e.g. regarding trade-offs in accuracy, comprehensiveness and simplicity, or alignment with comparable harmonization initiatives in sectors other than the electromobility one. We now encourage the LCA community to use this study as a blueprint towards improved practices, whether harmonization is key, such as for comparative LCAs of vehicles or parts, or of lower importance, such as in some research contexts.

ABSTRACT This article explores the connections between the London Assurance Company and slavery in the Atlantic world in the 1720s and 1730s. Relying on new archival sources, it offers a more specific accounting of the London Assurance’s underwriting of ships engaged in the trade in enslaved persons and those carrying goods to and from plantation colonies. It adds to our understanding of the connections between London’s insurance industry and the world of slavery by looking at financial investments. Previous studies of insurance and slavery have focused on underwriting, while this article encompasses underwriting and investing. Understanding how the London Assurance engaged with Atlantic slavery sheds further light on two long-term processes. First, it helps us understand slavery’s role in London’s development as a financial centre. The London Assurance functions as a case study, revealing the multiple avenues through which financial services firms engaged with slavery, and how those activities connected to other firms and financial services in the City. Second, appreciating the international elements of the London Assurance’s business shows how metropolitan-based financial interests used connections to slavery to advance British economic interests abroad without the support of formal empire.

Recent years have seen enormous progress in the field of advanced therapeutics for the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). In particular, four antisense oligonucleotide (ASO) therapies targeting various DMD-causing mutations have achieved FDA approval, marking major milestones in the treatment of this disease. These compounds are designed to induce alternative splicing events that restore the translation reading frame of the dystrophin gene, leading to the generation of internally-deleted, but mostly functional, pseudodystrophin proteins with the potential to compensate for the genetic loss of dystrophin. However, the efficacy of these compounds is very limited, with delivery remaining a key obstacle to effective therapy. There is therefore an urgent need for improved ASO technologies with better efficacy, and with applicability to a wider range of patient mutations. Here we discuss recent developments in ASO therapies for DMD, and future prospects with a focus on ASO chemical modification and bioconjugation strategies.

Este breve ensayo pretende, con base bibliográfica y experiencial, discutir un tema que se va tornando frecuente y que se entrelaza profundamente con la razón de ser y las condiciones de trabajo de docentes, estudiantes y cuerpos directivos. Parte, por supuesto, de algunas definiciones que enmarcan el análisis y de consideraciones en aspectos centrales, todos relacionados con la finalidad de la educación y los valores que la orientan o que deberían orientarla

Appeals are a crucial part of Europe’s asylum system but they remain poorly understood. Building on insights and perspectives from legal geography and socio-legal studies, this book shines a light on what takes place during asylum appeals and puts forward suggestions for improving their fairness and accessibility. Drawing on hundreds of ethnographic observations of appeal hearings, as well as research interviews, the authors paint a detailed picture of the limitations of refugee protection available through asylum appeals. Refugee law can appear dependable and reliable in policy documents and legal texts. However, this work reveals that, in reality, myriad social, political, psychological, linguistic, contextual and economic factors interfere with and frequently confound the protection that refugee law promises during its concrete enactment. Drawing on evidence from Austria, Belgium, France, Germany, Greece, Italy and the United Kingdom, the book equips readers with a clear sense of the fragility of legal protection for people forced to migrate to Europe. The book will appeal to scholars of migration studies, legal studies, legal geography and the social sciences generally, as well as practitioners in asylum law throughout Europe and beyond. This book is freely available as a downloadable Open Access PDF at https://www.taylorfrancis.com under a Creative Commons Attribution-Non Commercial-No Derivatives (CC-BY-NC-ND) 4.0 license.