Seven years passed since the discovery of lin−4’s unique properties and then, around the turn of the millennium, the research floodgates opened. This chapter tracks the nascent field of microRNA research, the frenetic race to discover and catalogue new microRNAs and find the organisms in which they were made. MicroRNAs held a prominent position in evolution, their number and diversity expanding at key transitions to more complex life, including for our own species, Homo sapiens. MicroRNAs, it would become clear, are the genome’s solution to how to control the natural fluctuations, randomness and noise in gene expression. The chapter also covers the pivotal experiments that laid the ground rules for how microRNAs work and revealed their effects on gene expression. Along the way, a selection of the scientific toolkit gets special attention, including some of the models used to find microRNAs and the technologies that would prove that microRNAs, despite their small size and limited number in genomes, controlled the vast majority of gene activity in our cells.

This chapter provides details of the molecular techniques in use to detect viral RNA and DNA, including PCR, NAAT, nested PCR, multiplex PCR, real time PCR, quantitative PCR, LAMP, TMA, microarrays, sequencing and point-of-care tests and their utility.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to new variants: viruses with different sets of mutations, some of which have increased transmissibility and immune escape. Detecting and monitoring new variants was made possible by intensive, global genomic surveillance efforts, including sequencing over 1.2 million SARS-CoV-2 genomes in the first pandemic year. Crucial to these efforts was the Rapid Acceleration of Diagnostics (RADx®) Variant Task Force, which was established in 2021 to monitor variants and assess the efficacy of RADx technologies against new variants. Major accomplishments of the RADx Variant Task Force include the establishment of the ROSALIND Diagnostic Monitoring system to identify mutations, the creation of an extensive biobank of sequenced samples, laboratory testing of RADx technologies against new variants as they emerged, and epitope mapping to identify mutations likely to affect an assay’s performance. Key lessons learned include (1) the need for very early establishment of pathogen sequencing, analysis, and data sharing; (2) the importance of both in silico and wet laboratory assessment of diagnostic assays; and (3) the benefits of interdisciplinary collaboration of government, academia, and industry.

This chapter reviews recent developments that reflect a convergence of work in various branches of linguistics and psycholinguistics around the implications of the incremental sequencing of speech units for understanding grammar and the cognitive processing that underlies the production, comprehension, and interpretation of utterances. Notions from Functional Discourse Grammar are used to present a view of syntactic structure as arising from the incremental extension of holophrases, i.e., minimal utterances. By prioritizing the timecourse of language processing, the chapter interprets syntactic hierarchy as arising from chunk-and-pass operations supported by predictive processing. Spoken dialogue is identified as the primary arena for these processes, with grammaticality subordinated to situational appropriateness. Linguistic data are seen as protocols of joint action aimed at the incremental co-creation of meaning. All of these notions make essential reference to context as constantly active, prior to and during the utterance of the linguistic signal, and as a crucial component of the operations and processes that take place in verbal interaction.

Physical time refers to five context-independent elements of time: tempo, duration, timing, sequencing, and stages. It makes two contributions. It refines the analysis of historical time by focusing on the rhytms in which it unfolds. It thus supplements the analysis of what changes in content by paying attention to how it changes in rhythm. It also refines causal analysis by treating the elements of physical time that produce distinct causal effects; these are frequently overlooked by linear notions of causality. CHA employs both physical time and historical time, and this distinguishes it from other methodologies. It configures these elements of time in distinct ways, which define the three strands of CHA: eventful, longue durée, and macro-causal analysis.

Text comprehension and picture comprehension can be synthesized into a common conceptual framework which differentiates between external and internal descriptive and depictive representations. Combining this framework with the human cognitive architecture including sensory registers, working memory, and long-term memory leads to an integrated model of text and picture comprehension. The model consists of a descriptive branch and a depictive branch of processing. It includes multiple sensory modalities. Due to a flexible combination of sensory modalities and representational formats, the model covers listening comprehension, reading comprehension, visual picture comprehension, and sound comprehension. The model considers text comprehension and picture comprehension to be different routes for constructing mental models and propositional representations with the help of prior knowledge. It allows us to explain the effects of coherence, text modality, split attention, text–picture contiguity, redundancy, sequencing, and the effects of different types of visualization.

This chapter introduces the readers to case study research, with the help of historical and contemporary examples. We define case study research and briefly discuss the existing case study designs. Subsequently, we explain the main purpose of this book: To take case study research to the next level by discussing the combinations of different case study designs in the same study, which we call "sequencing case study designs." Furthermore, we discuss the building blocks of case study designs, the strengths/weaknesses of archetypical designs, the conundrum surrounding the crafting/relaying of theoretical contributions, some concrete examples of designs, and the differences/similarities amongst different paradigmatic camps in case study research. We end the chapter by briefly introducing the contents of the subsequent chapters.

This chapter introduces health recovery processes, recommending realistic engagements backed by appropriate conceptual tools. Direct experience supported by the literature warns against linear narratives, ready-made solutions and missions accomplished! The nature of stresses and shocks, and their influence on health systems is discussed. The politics of transition and its implications are highlighted. Situation analysis, debate, and proposed intervention as the main drivers of a sound recovery process are reviewed. A situation analysis covers patterns, trends, and resource levels across a disrupted healthcare landscape including appraisal of vulnerabilities and strengths. An informed, contextualised debate regarding political settlement, demography, economy, privatisation, and urbanisation is needed with all stakeholders. Supporting health recovery processes entails seizing opportunities, while containing harmful drives. Realistic strategies and effective measures must be negotiated with overambitious stakeholders. The chapter concludes with advice on designing, managing, and evaluating recovery-oriented interventions, and readings to deepen the study of health recovery processes.

So far, we have focused on DNA types in which one allele is from the father and one from the mother. However, three other sources of DNA come from only one parent, and all can be employed in forensic testing. One is mitochondrial DNA (from the mother in all her children), and the other two are STR sites on the Y chromosome (from the father in his sons) and STR sites on the X chromosome (from the mother in her sons). These DNA sources are lineage markers, since they can be traced back generations through our family trees. Lineage markers are valuable in missing person cases where DNA from the person of interest is not available. Mitochondrial DNA (mtDNA) has been used in historical cases, such as identifying soldiers killed in past conflicts. We will explore these and other examples in this chapter.

This chapter discusses the remedies that are available under WTO law. It explains that the preferred solution to a dispute is a mutually agreed solution. If this is not possible, and the defending party does not implement any adverse rulings, the defending party may offer compensation (in the form of equivalent trade concessions). The last and least desirable option is retaliation, or the suspension of concessions. The chapter explains the procedures for each of these possible remedies, with a particular focus on the arbitration under Article 22.6 of the DSU of the amount of retaliation proposed by the complaining party. The chapter also discusses the “sequencing” problem arising out of the deadlines to request the right to retaliate in the DSU. Finally, the chapter discusses the special rules governing disputes over subsidies and the role played by suggestions by the panel and Appellate Body on implementation.

Institutions are essentially temporal, in the sense that, definitionally, they endure. Setting aside the conventional understanding of a historical institutionalism, we focus on the interplay of institutions and temporality. The chapter begins with a conception of time that is complex and social, and identifies four concepts amenable to deeper exploration: duration, tempo, and “temporal location,” which itself involves distinct notions of sequencing and timing. Institutions shape and are shaped by all of these aspects of temporality. The chapter surveys a range of institution-theoretic analyses, combining them in myriad ways via more complex notions such as the power of the institutional status quo, institutional intercurrence, punctuated equilibrium, critical junctures, and path dependence. While temporal approaches offer limited leverage on institutional origins, they show great strength in accounting for dynamic persistence and change, especially insofar as they supply means of understanding the layering and corresponding multiplicity of institutions of distinct temporal profiles operating at any given moment in social life.

In this chapter, we discuss problems in the single-stage or parallel-units environment. The problem statement is presented in Section 4.1. Three types of models are presented in Section 4.2 (sequence-based), Section 4.3 (continuous time grid-based), and Section 4.4 (discrete time grid-based). In Section 4.5, we present how batching decisions can be handled, and in Section 4.6 we discuss how the three types of models can be extended to handle a new feature, namely, general shared resources. Finally, in Section 4.7 we present extensions on the modeling of general resource constraints using discrete modeling of time. Building upon the material in Chapter 3, we illustrate how some of the modeling techniques introduced for single-unit problems can be extended to account for multiple units. Our goal is to outline some general ideas that the reader can apply to a wider range of problems.We focus on (1) problem features that are new, compared to the ones in single-unit problems (i.e., batching decisions and general shared resources); and (2) new modeling techniques that are necessary to account for these features.

This chapter introduces scheduling in the simplest production environment, the single-unit environment. The statements of different problems are presented in Section 3.1. Two different types of MIP sequence-based models are presented in Section 3.2. Section 3.3 discusses models based on a continuous time grid, while Section 3.4 presents models based on a discrete time grid. A number of extensions are discussed in Section 3.5, and we close in Section 3.6 with some general remarks.