Chapter 7 led us through the maze of signalling pathways in cancer cells to a core network that lies at the heart of tumour development and, predictably, features the most prominent oncogenes and tumour suppressors. This established a solid molecular base upon which to review the critical cancer questions: (1) how to detect them, (2) once detected, whether the course of their progression can be predicted, and (3) where we are in terms of treatment by drugs (chemotherapy). The first two are considered in this chapter before we turn to the current chemotherapy situation in Chapter 9 and future prospects in Chapter 10.

Chapter 6 described the phenotypic features that characterise tumour cells and the underlying molecular changes that subvert normal signalling pathways (Chapter 4) through the mutations acquired in the cancer cell genome (Chapter 5). As we’ve seen, the major ‘drivers’ of cancer development arise in pathways from receptor tyrosine kinases (RTKs) that ultimately control cell division. Thus, for example, aberrant activity of the RAS–mitogen-activated protein kinase (MAPK) pathway occurs frequently across a broad spectrum of cancer types. However, cancer-promoting mutations occur in other signalling pathways and ultimately they can affect all aspects of cellular behaviour. The molecular details of most of these pathways and how they can be subverted in cancers are now well established. The integration between diverse pathways creates a picture of a complex ‘information network’ rather than of discrete, linear systems. Despite the multiplicity of signalling pathways that can be involved, the tumour cells that emerge as the result of appropriate groups of mutations are phenotypically similar in that they share the characteristics discussed in the previous chapter. This suggests that the diverse pathways converge on a ‘central axis’, and in this chapter we’ll look first at the central defenders that do indeed constitute the heart of our protection mechanisms against cancer. We’ll then overlay the major pathways from receptor to nucleus to show how they impact on the central axis and dissect from this complex map each of the pathways in turn to introduce the key players. The intention is not show all known detail but to convey the principle features of the pathways with particular emphasis on identified proto-oncogenes and tumour suppressors.

In the final chapter of this book, we return to the concept of accent, by looking at how we develop and use our accent across time and space. The chapter then provides you with resources for more advanced study of English and phonology, by presenting a range of online websites and databases with speech samples, as well as movies and TV series to provide exposure to different varieties of English. The discussion then focuses on pragmatic considerations in data collection, including the use of free software programs such as Audacity and PRAAT to record and analyse speech. The chapter then reviews different types of data that can be collected for phonetic and phonological analysis, including word lists, reading passages, and conversational data, with a discussion of the benefits and drawbacks of using each type of data. In the final section of the chapter, you are guided through exercises to check your understanding of the content of the chapter.

This chapter introduces you to English vowels, and variation in vowel inventories across varieties of English. The discussion will first focus on English phonetics – the production of individual speech sounds. We will begin by examining the articulatory features used to classify and describe vowels, namely tongue height, front/backness of tongue articulation (also called advancement), degree of lip rounding/spreading. In this overview, we will also examine vowel inventories across a range of languages to understand which vowels are most common cross-linguistically, and why.

In the next sections of the chapter, we will focus on English vowels by first introducing the types of vowels that exist in different varieties of English. We will then examine the vowel inventories in a range of Englishes, among them OVEs including American, British, Australian, and New Zealand Englishes, and NVEs such as African, Asian, and Caribbean Englishes. We will also discuss the concepts of phoneme, phone, and allophone in this chapter, which sets the stage for exploring the concept of phonology through vowel variation within varieties of English, and phonological rules that govern this variation.

We study our first cryptographic tasks: secure encryption of a quantum state. We describe the classical one-time pad and present its quantum extension, the quantum one-time pad, which achieves perfectly secure quantum encryption. Before studying this task, we extend the mathematical formalism introduced in Chapter 1 by studying density matrices, general measurements on quantum states, and the partial trace operation.

The primary manuscripts that preserve Plato’s text give to the dialogue that is now his most widely read the title and subtitle Πολιτεία ἢ περὶ δικαίου.1 The title is attested as early as the time of Aristotle, who refers to his teacher’s work by that name on a number of occasions.2 The subtitle, like that for each of Plato’s works, appears also in the catalogue of his dialogues arranged in tetralogies by Thrasyllus in the first century (D.L. 3.57–61), although the practice of affixing subtitles is likely to have originated with booksellers already in the fourth century.3 The standard translation of Πολιτεία in English and other modern languages has been influenced by the title of Cicero’s De re publica, written in emulation of its Greek predecessor. But “Republic” is not an entirely satisfactory rendering of the title of Plato’s dialogue. The word πολιτεία designates that arrangement, whatever form it might take, that a people chooses to adopt in order to live together in a community (which, for a Greek, is a polis). That is the sense the word has when Plato puts it into the mouth of Socrates at the beginning of Timaeus, written some years after Republic. There Socrates refers to a summary of the presentation that he gave to his companions the previous day as “concerned with the political system (περὶ πολιτείας) and its citizenry that seemed to me would be the best.”4 The material covered in the summary includes several of the distinctive ideas for which Republic is most famous: the division of society into classes according to natural ability; the philosophically rigorous program of education for the Guardians, who are to repudiate the possession of private property; the equality of men and women with regard to their capacity to contribute to the state; the abolition of the “nuclear family,” so that spouses, siblings, parents and children are to be considered as common to all those of the appropriate age; eugenic management by the state of mating among the citizens and the production of children; official monitoring of children to determine who is worthy of elevation to, or demotion from, the ranks

How do we define knowledge, and, crucially for cryptography, ignorance? In this chapter we lay the basis for future security proofs by formalizing the notion of knowledge of a quantum party, such as the memory of an eavesdropper, about a classical piece of information, such as a secret key. For this we introduce an appropriate measure of conditional entropy, the min-entropy, and introduce important tools to bound it using guessing games.

Another way of examining the patterns among objects based on multiple variables is to plot the objects in multidimensional space based on their pairwise dissimilarities. We first describe multidimensional scaling as a very flexible ordination method that can be based on a wide range of dissimilarities. We also introduce cluster analysis based on dissimilarities, where the pattern among objects is represented in a tree-like plot called a dendrogram. We show how to correlate dissimilarities to other continuous and/or grouping variables and fit linear models that treat the dissimilarities as responses modeled against continuous or categorical predictors.