Conclusions and Policy Implications

The work presented in this volume is a compilation of research highlights that represent numerous studies carried out by researchers within the Energy Governance Work Package (WP4) of the Swiss Competence Center for Energy Research, Society and Transition (SCCER CREST). As our Introduction has illustrated in detail, these researchers worked together under common scientific interests in providing recommendations to overcome governance challenges in the course of the energy transition in Switzerland. Despite the variety of disciplines involved in this group, the conscious decision not to over-precise the shared notion of governance has successfully guided this challenging but fruitful four-year collaboration. These findings should help identify basic designs and structural principles of good energy governance, i.e., governance that is more effective, efficient, and transparent. The conclusion chapter summarizes these guiding principles and further challenges that emerged from our research in the context of Swiss energy governance.

New Horizons: Next-Generation Insulin Analogs: Structural Principles and Clinical Goals

Design of “first-generation” insulin analogs over the past three decades has provided pharmaceutical formulations with tailored pharmacokinetic (PK) and pharmacodynamic (PD) properties. Application of a molecular tool-kit—integrating protein sequence, chemical modification and formulation—has thus led to improved prandial and basal formulations for the treatment of diabetes mellitus. Although PK/PD changes were modest in relation to prior formulations of human and animal insulins, significant clinical advantages in efficacy (mean glycemia) and safety (rates of hypoglycemia) were obtained. Continuing innovation is providing further improvements to achieve ultra-rapid and ultra-basal analog formulations in an effort to reduce glycemic variability and optimize time in range. Beyond such PK/PD metrics, next-generation insulin analogs seek to exploit therapeutic mechanisms: glucose-responsive (“smart”) analogs, pathway-specific (“biased”) analogs, and organ-targeted analogs. Smart insulin analogs and delivery systems promise to mitigate hypoglycemic risk, a critical barrier to glycemic control, whereas biased and organ-targeted insulin analogs may better recapitulate physiologic hormonal regulation. In each therapeutic class considerations of cost and stability will impact utilization and global distribution. This review highlights structural principles underlying next-generation design efforts, their respective biological rationale and potential clinical applications.

Structural features within the NORAD long noncoding RNA underlie efficient repression of Pumilio activity

It is increasingly appreciated that long non-coding RNAs (lncRNAs) carry out important functions in mammalian cells, but how these are encoded in their sequences and manifested in their structures remains largely unknown. Some lncRNAs bind to and modulate the availability of RNA binding proteins, but the structural principles that underlie this mode of regulation are underexplored. Here, we focused on the NORAD lncRNA, which binds Pumilio proteins and modulates their ability to repress hundreds of mRNA targets. We probed the RNA structure and long-range RNA-RNA interactions formed by NORAD inside cells, under different stressful conditions. We discovered that NORAD structure is highly modular, and consists of well-defined domains that contribute independently to NORAD function. We discovered that NORAD structure spatially clusters the Pumilio binding sites along NORAD in a manner that contributes to the de-repression of Pumilio target proteins. Following arsenite stress, the majority of NORAD structure undergoes relaxation and forms inter-molecular interactions with RNAs that are targeted to stress granules. NORAD sequence thus dictates elaborated structural domain organization that facilitates its function on multiple levels, and which helps explain the extensive evolutionary sequence conservation of NORAD regions that are not predicted to directly bind Pumilio proteins.

Digital Capitalism and Critical Media Education

Digital capitalism has produced a new concentration of capital, knowledge, and power unprecedented in history. Quantification is fundamental to digital and capitalistic structural principles. In view of a comprehensive quantification and measurement of life and society, questions of meaning and significance must be asked beyond quantifying process structures. The first part of the article identifies capitalistic and digital structural principles, showing affinities between both principles. The second part points out central challenges and problem areas of digital capitalism. The third part discusses the manoeuvres of the IT industry in Germany to gain more influence on the education sector. Against the background of these developments, the last part outlines the need for alternative pathways and presents dimensions of a critical media education.[1] [1] The article is based on two German language publications (Niesyto, 2017a, 2021).

What is Mereology?

This chapter provides a brief illustration of the centrality of part-whole inquiry throughout the history of philosophy, West and East. It explains two original motivations for the contemporary formal explorations of mereological systems. Husserl’s approach, stemming from Brentano, sought to treat part-whole relations as formal ontology – comprising a set of general structural principles applying to any objects whatsoever. Leśniewski’s approach was motivated by nominalism and the search for an alternative foundation for mathematics not beset by the paradoxes of naïve set theory. Some attention is paid to the different uses of ‘part’ in natural language and to whether mereology should be thought of as providing a single, overarching account. The final section details the logical machinery used throughout the book.

Phthalocyanine pigments: general principles

This chapter describes some of the fundamental chemical and structural principles underlying the phthalocyanine system. Historically, phthalocyanines had been isolated as insoluble blue products in the early twentieth century, although the structures were not established at the time. After the serendipitous re-discovery of metal complex phthalocyanines by industry, and the elucidation of their structures, copper phthalocyanine (CuPc) pigments were introduced industrially in the 1930s to become, and remain, by far the most important blue and green organic pigments, finding almost universal use as colorants for paints, printing inks, plastics, and a wide range of other applications. The phthalocyanines have become one of the most extensively studied classes of organic compounds, because of their unique molecular structures, light absorption properties that produce strong, bright colors, and their exceptionally high stability. While their dominant use is as colorants, they are also of interest for a range of other applications, for example in electronic devices, biological applications, and as catalysts.

Structure-based design of stabilized recombinant influenza neuraminidase tetramers

Influenza virus neuraminidase (NA) is a major antiviral drug target and has recently reemerged as a key target of antibody-mediated protective immunity. Here we show that recombinant NAs across all non-bat subtypes adopt various tetrameric conformations, including a previously unreported 'open' state that may help explain poorly understood variations in NA stability across viral strains and subtypes. We used homology-directed protein design to uncover the structural principles underlying these distinct tetrameric conformations and stabilize multiple recombinant NAs in the 'closed' state. In addition to improving thermal stability, conformational stabilization improved affinity to protective antibodies elicited by viral infection, including antibodies targeting a quaternary epitope and the broadly conserved catalytic site. The stabilized NA proteins can also be integrated into viruses without affecting fitness. Our findings provide a deeper understanding of NA structure, stability, and antigenicity, as well as a roadmap towards structure-based discovery of NA-directed therapeutics and vaccines.

Foreign Subsidies, Distortions and Acquisitions

The world trade system’s bedrock was laid more than seventy years ago and its architecture and structural principles were shaped by the societal paradigm of western democracies. The last two decades have seen the admission of various government-dominated economies to the WTO. This raised serious paradigmatic challenges. The system tailored to the needs and characteristics of western democracies proved to be inadequately equipped to frame government-dominated economies. This paper addresses one of these new challenges: government subsidies. First, it gives an overview of the status and treatment of product and service subsidies in WTO law and the gaps and shortcomings that result in the system’s failure to address trade-distortive state aids. Second, it examines the European Commission’s White Paper on Levelling the Playing Field as Regards Foreign Subsidies (“White Paper”), which ushers a comprehensive European response to the problems raised by subsidization in international trade. Third, the paper analyzes the WTO framework that governs and confines unilateral actions targeting foreign subsidies. Fourth, the paper makes a proposal for a complementary way to address the world trade system’s “subsidies problem”.