bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpretation: hermeneutics
Authors: Clark Timothy
Published: November 2023

Hermeneutics is the theory of interpretation: of what it is to interpret a text and of how that interpretation may validate itself. In the eighteenth and parts of the nineteenth centuries, the context for such issues was predominantly religious: hermeneutics meant, primarily, discussion of the possible methods of achieving a correct interpretation of a text, especially of the Bible. Today, the crucial questions in hermeneutics remain: what do we mean when we say that someone ‘understands’ a text? For instance, does understanding mean reproducing exactly what the text says on its own terms, or does it mean interpreting it in terms of its author’s life or its social or historical context? Alternatively, might it mean measuring the text against contemporary knowledge and finding it either wanting or valuable? Secondly, how can genuine understanding, however conceived, overcome the obstacles of both distance in historical time and often distance in culture between the text and its reader? In the twentieth century, questions about the nature of interpretation also increasingly overflowed traditional boundaries between intellectual disciplines, and took centre-stage in the question of the difference between kinds of understanding at work in the natural sciences and in the humanities.
Literature into culture: Cultural Studies after Leavis
Authors: Jordan Glenn , Weedon Chris
Published: November 2023

Over the last thirty years, Cultural Studies has developed into a diverse and lively international intellectual field. As Stuart Hall, one of its founders, has put it: ‘Today, cultural studies programmes exist everywhere, especially in the United States . . . where they’ve come to provide a focal point for interdisciplinary studies and research, and for the development of critical theory.’ The institutional success of Cultural Studies is demonstrated by a number of major international journals, global and national associations, increasing numbers of international conferences, academic programmes, and publishers’ catalogues advertising new and essential publications in the field. As a field of study, Cultural Studies has had important effects on the study of literature. It has challenged the idea of canonical literature, and affected the way literary texts are theorized and read. It has introduced cross- and interdisciplinary perspectives. It has sought to theorize the role of literature in society in new ways, and to look at literary texts in relation to cultural institutions, cultural history, and other cultural texts, forms, and practices. It has further focused attention on the circuit of literary production.
Reconstructing historicism
Authors: Hamilton Paul
Published: November 2023

All critics are historicist up to a point. The pastness of the texts that we interpret demands accommodations of critical approach to negotiate historical differences. Equally, if a work of literature speaks to us now with a contemporary relevance, that inevitably plays some part in our evaluations. So far, this give and take is only what one would expect. Historicism becomes more interesting when it addresses questions of perennial philosophical importance, such as the relations between fact and fiction in history and aesthetics. Are historical and aesthetic discourses necessarily opposed in their tasks, or do they offer each other mutual support? Traditionally, the aptness of literary skills to the evocation or re-creation of the past has helped to distinguish historical explanations from scientific ones, for which fictional assistance is usually thought to be a disadvantage.
Sexualities
Authors: Purvis Tony
Published: November 2023

In the last two decades, the breadth of output in literary and cultural criticism which has investigated the specificities and constructions of human sexualities is vast, and it is a corpus which continues to grow. It is unusual for undergraduate programmes in the arts, humanities, and social sciences not to offer courses which explore some aspect or representation of sex, sexuality, or sexual desire. The critical attention to, and analysis of, cultural texts as well as to sexual practices has been matched by a prodigious theoretical output. Moreover, activist campaigns, lobbies of parliaments, and ‘queer’ coalitions have mobilized around issues such as sexual abuse and homophobic bullying, religious persecution and fundamentalism, HIV and AIDS, the age of consent, and equal opportunities at work. Sex and sexualities are theorized, televisualized, and talked about more than ever, or so it seems.
The responsibilities of the writer
Authors: Burke Sèan
Published: November 2023

Like writing, reading so often begins in romance and ends in pragmatism. On first looking into the Ion of Plato or Coleridge’s ‘Kubla Khan’, the idea of the poet as divinely inspired enthrals. Only later do we recognize that such celebrations are of a piece with the banishment of the poets. The line ‘Weave a circle around him thrice’ we either neglect or hazily register in magical, runic terms. Only on rereading do we discern the theme of exclusion, of quarantine, the structure by which society simultaneously celebrates and ostracizes its artists; only by setting Plato’s Republic beside his Ion can we recognize that the very irrationality that sets the poet apart also makes the poet accountable to—or excluded from—a polis constructed according to the principles of philosophical rationalism.
Theories of the gaze
Authors: Hawthorn Jeremy
Published: November 2023

[Fred’s mother Mrs Vincy] never left Fred’s side when her husband was not in the house, and thus Rosamond was in the unusual position of being much alone. Lydgate, naturally, never thought of staying long with her, yet it seemed that the brief impersonal conversations they had together were creating that peculiar intimacy which consists in shyness. They were obliged to look at each other in speaking, and somehow the looking could not be carried through as the matter of course which it really was. Lydgate began to feel this sort of consciousness unpleasant, and one day looked down, or anywhere, like an ill-worked puppet. But this turned out badly: the next day, Rosamond looked down, and the consequence was that when their eyes met again, both were more conscious than before. There was no help for this in science, and as Lydgate did not want to flirt, there seemed to be no help for it in folly. It was therefore a relief when neighbours no longer considered the house in quarantine, and when the chances of seeing Rosamond alone were very much reduced.
Moral Sense and Virtue in Hume’s Ethics
Authors: Russell Paul
Published: November 2023

On the face of it, Hume’s understanding of the relationship between virtue and moral sense seems clear enough. According to Hume, a virtue is a quality of mind or character trait that produces approval, and vice a quality of mind that produces blame ( T 614; cp. 473,575). This relationship between virtue and vice and our moral sentiments is described and analysed by Hume as part of his wider and more general account of the mechanism of the indirect passions. Any quality or object, Hume maintains, that is closely related to a person and that produces either pleasure or pain will give rise to an indirect passion. In the case of pride and humility the quality or object must be closely related to myself, whereas in the case of love and hate the quality or object must belong or be related to some other person. When the quality or object is pleasant we shall feel either pride or love, when it is painful I feel either humility or hate.
Manners, Morals, and Practical Wisdom
Authors: Stohr Karen
Published: November 2023

So says Elizabeth Bennet upon her realization that the charming Mr Wickham is a cad underneath, and that Mr Darcy, for all his haughtiness and unpleasant social manners, has a fundamentally good moral character. It is not surprising that she should be so deceived; what is surprising, at least to modern readers, is that Elizabeth apparently expects manners and morals to track one another. In the world of Jane Austen’s fiction, it is not simply a happy accident that good manners and good morals are ordinarily found together; rather, a person’s manners are the outward expression of her moral character.
Rethinking Literary History: Idealism, realism, and the birth of modernism
Authors: Moi Toril
Published: November 2023

For anyone interested in the emergence of modernism, Ibsen’s writings are a find: an undisturbed archaeological site concealing a perfectly preserved genealogy of modernism. Ibsen’s career spans the whole of the second half of the nineteenth century. In the 1850s Ibsen wrote romantic tragedy and national romantic drama; by the 1890s he had become Europe’s most famous avant-garde playwright, hailed by the emerging modernist generation as their leader and lodestar. To trace Ibsen’s aesthetic transformations is to trace the birth of European modernism.
Pindar, Athletes, and the Early Greek Statue Habit
Authors: Smith R R R
Published: November 2023

My subject is victor statues at Olympia and elsewhere in the fifth century BC, seen as an early and important part of the statue habit in antiquity. They are a good example of how statues marked special priorities, both by their numbers and by their visual styling. Naked victor statues were to the fifth century what honorific statues wearing the citizen suit of himation and chiton were to the Hellenistic period—defining components of their times. Pindar stands behind the victor statues as a key text for the whole phenomenon.
Pindar’s Poetry as Poetry: A Literary Commentary on Olympian 12
Authors: Silk Michael
Published: November 2023

The simplest way of illuminating Pindar’s poetry ‘as poetry’ is through a close reading of a Pindaric ode. For this purpose Olympian 12 is of a convenient size (it is one of Pindar’s shortest victory odes), and one on which, conveniently, there is no satisfactory commentary. The text of the poem is not controversial, though my translation may be.
The broad conceptualization of work and health
Authors: Mustard Cameron
Published: November 2023

Work-related health interventions in industrialized countries have been predominantly concerned with the regulation of materials and processes that are potentially hazardous to the health of workers. Occupational health protection efforts have produced immensely safer, cleaner, and healthier work environments [see Chapter 6 for brief descriptions of the occupational health and safety (OHS) systems in several countries]. Workers’ compensation systems in developed economies have frequently used fiscal incentives to influence firm-level practices concerning the prevention and rehabilitation of compensable occupational injuries and diseases. There is evidence that these incentive-based policies are effective instruments for influencing firm behaviour (Hyatt and Thomason 1998).
Lessons from the literature on valuing reductions in physical risk
Authors: Cookson Richard , Dorman Peter
Published: November 2023

The economic literature on valuing reductions in physical risk (or ‘valuing safety’, for short) concerns attempts to value the prevention of injury and disease in economic evaluations. There are several general literature reviews (Viscusi 1993; Beattie et al. 1998a) and textbooks (Jones-Lee 1989; Viscusi 1992; Dorman 1996) on the topic. A more comprehensive review from which this chapter was developed is also available as a working paper (Cookson and Dorman 2008).
Study design
Authors: Gnam William , Robson Lynda , Kohstall Thomas
Published: November 2023

This chapter considers issues of study design in determining the effectiveness of occupational health and safety (OHS) interventions. We focus on how study design may affect the validity of an estimate of the net intervention effect (defined as the difference between the outcomes of the intervention and those of the alternative to which it is being compared). This discussion is directly relevant to economic evaluations since estimates of net value are derived from estimates of effects. We cover overall design issues but not other important specific aspects such as recruitment or data collection (see Chapter 7 for details).
Introduction
Authors: Thomas Frédéric , Guégan Jean-François , Renaud François
Published: November 2023

What are the effects of parasites and pathogens on the ecology and evolution of free-living organisms? This is a huge question! The time when parasites were of interest only to parasitologists is definitively over. The influence of parasites on the evolution of free-living organisms is for some scientists a central research topic and for others an inescapable factor, given that all organisms are affected by parasites. While past studies have mainly focused on the direct effects of pathogens on the fecundity and survival of their hosts, current research shows a surprising number of unexpected consequences for various host traits such as behaviour, morphology, and/or physiology.
Parasitism and the evolution of life-history traits
Authors: Michalakis Yannis
Published: November 2023

It is a well-known fact that a parasitized host is not just like any other host. Alterations due to parasitism, whether behavioural or physiological, feed back on the host’s life-history traits: the traits pertaining to survival and reproduction. By definition, such alterations have a central role in the ecology and evolution of the host, a good enough reason for any research project on host–parasite interactions to include at some stage characterization of the effects of the parasite on its host’s life-history traits. Several chapters of this book refer to various aspects of such parasite-induced alterations.
Taking Socrates’ Question Seriously
Authors: Haybron Daniel M
Published: November 2023

Definitions of happiness are not, in themselves, particularly exciting. Like opinions and a certain rude part of the anatomy, everybody’s got one. Not only that, but on the typical definition that treats happiness as a purely psychological affair, you could be happy but not have a good life at all: you could, for instance, lead a sham life hooked up to an “experience machine,” à la The Matrix, that offers whatever experiences you—who would think they were real—might want. Most people recoil at the thought of permanently plugging into such a machine. Apparently our mental states are not the only things that matter. From such observations one might infer that philosophical work on happiness holds little promise: its subject matter is neither interesting nor important.
Pleasure
Authors: Haybron Daniel M
Published: November 2023

One might have thought happiness and pleasure were two very different things. Certainly the temptation to regard the terms as interchangeable is less than overwhelming. Yet the best-known theories of happiness ask us to regard these things as more or less identical: to be happy just is for one’s experience to be, on balance, more pleasant than not. This is hedonism in its traditional reductive form, as found in the works of Bentham, Sidgwick, Brandt, and many others. We can distinguish variations on the theme. But the root idea, shared by all hedonists, is that happiness consists solely in pleasant states of mind, or pleasantness itself (and freedom from unpleasantness or unpleasant states, a nicety I will usually omit hereafter).
Emotional State
Authors: Haybron Daniel M
Published: November 2023

Probably most languages have some counterpart to ‘happiness’ in its oldest meaning, a term for prosperity, good fortune, or “good hap”—roughly, well-being. This is the concept likely invoked at weddings, births, and other major events where we wish, utterly vaguely, for the individuals’ lives to go well for them: “May the newlyweds meet with happiness in their life together.” Once upon a time, this may have been conceptual apparatus enough for the general lot: the life of enviable fortune tended to be just that — mainly a matter of luck — with little point in troubling yourself about how well you were actually doing in that regard. Moreover, your well-being was at best a secondary concern. What mattered then — and still today in many parts of the world — was less a matter of personal fulfillment and more a matter of your family’s material wealth and social standing. You married for cattle, not love, and he who died with the most cows won. If you didn’t like cows, or your spouse, tough; no one was asking.
Limitations of the technique
Authors: Marhofer Peter
Published: November 2023

Every serious analysis of a new method should also consider its potential limitations. For ultrasound-guided regional anaesthesia, these can be divided into technical and non-technical limitations.

Physical law dictates that the deeper the anatomical structures, the lower the ultrasound frequencies needed to visualize them. Therefore, direct nerve visualization for deep blocks, such as psoas compartment blockade, is not always possible. Nevertheless, the identification of adjacent structures (e.g., the lower pole of the kidney during psoas compartment blockade) increases the margin of safety for deep blocks.
Getting past the traditional concepts
Authors: Berthoz Alain , Petit Jean-Luc , Macann Christopher
Published: November 2023

In this chapter we are going to try and develop a theoretical posture for the physiology of action. The reader may wonder why we use an expression paradoxically associating posture with theory. Posture does not just describe the relative position of the parts of our body. The Russian physiologist Bernstein wrote that posture is a ‘preparation for action’. Posture is an expression of emotions and a reflection of intentions; it is influenced by our culture and by our social training. The fact is that physiologists do not always have the time, or the need, to formulate and legitimate the concepts and procedures employed in their empirical science, even if in fact their hypotheses are driven by an implicit epistemology.
Prolegomena to a theory of constitution
Authors: Berthoz Alain , Petit Jean-Luc , Macann Christopher
Published: November 2023

Any reader who upholds clear-cut distinctions will no doubt to ask whether we are not confusing what we propose under the heading of ‘new ideas in the field of the physiology of action’ with a retrospective commentary on the history of philosophy of the kind of ‘a little-known aspect of transcendental philosophy from Kant to Husserl’. Our basic idea is, however, quite simple and can possibly be expressed in such a way as to preclude any ambiguity. We find, in the philosophical tradition, a kinaesthetic theory that is still (to our knowledge) largely unknown, and so little exploited, in spite of the contribution it can be shown to make to the cognitive sciences.
Greeks and Latins: Ethno-Religious Identity
Authors: Shawcross Teresa
Published: November 2023

According to the Chronicle of Morea, the knights who settled in the Morea with the initial conquest and their descendants continued to identify closely with other westerners. Both in B (§182) and in H (vv.2550–3), Prince Geoffroy II de Villehardouin justifies his marriage to the daughter of the Latin Emperor of Constantinople by pointing out to his father-in-law, who opposed the match, that the two parties were not only of equal social standing, but also of French ancestry. Guillaume II de Villehardouin, although himself born and raised in Greece, is said to have been overjoyed at the conquest of the Kingdom of Sicily by Charles I d’Anjou, brother to the French king, because it meant that another ruler of the same race would govern territory neighbouring that of the Principality (H vv.6265–71 and B § 441). This sense of solidarity with the West, and especially with the nobility of France, is associated in the Chronicle with the status of the conquerors and settlers as foreigners in the Aegean world. Thus, in B, the future Geoffroy I de Villehardouin prefaces his advisory speech to Guillaume I de Champlitte regarding the conquest of the Peloponnese with a remark reminding his lord that he has entered an alien environment, far from both the friends and the enemies to whom he had previously been accustomed (§ 108). In H, Guillaume II de Villehardouin addresses the Emperor Michael VIII Palaeologus in a manner which draws attention to a lack of familiarity with Greek customs and with the Byzantine court in particular (vv.4256–65).
Some Major Challenges
Authors: Gerald O’Collins S J
Published: November 2023

God brought forth the Word as a root brings forth a shoot, a spring the river and the sun its beam. (Tertullian, Adversus Praxean) You preach to me God, born and dying, two thousand years ago, at the other end of the world, in some small town I know not where; and you tell me that all who have not believed in this mystery are damned. (Jean-Jacques Rousseau, E´mile) In the light of Christian faith, practice, and worship, that branch of theology called Christology reflects systematically on the person, being, and activity of Jesus of Nazareth (c.5 bc–c.ad 30).
The Resurrection
Authors: Gerald O’Collins S J
Published: November 2023

The resurrection of Christ has been allegorised and volatilised in nearly every imaginable way, but the fact remains that neither Jesus himself nor the Christian community can manifest a distinctive character or true identity apart from the resurrection event itself, where faith, hope and love are given their vindication and new birth right. (Richard R. Niebuhr, Resurrection and Historical Reason) The resurrection of Jesus supplies us with enough questions to inspire writing at least a generous section for a theological library.
The Son of God
Authors: Gerald O’Collins S J
Published: November 2023

One is tempted to say that more happened [in Christology] in this period of less than two decades than in the whole of the next seven centuries, up to the time when the doctrine of the early church was completed. (Martin Hengel, The Son of God) The Gospel of Mark illustrates two possible extremes in presenting the sonship of Jesus. He can be interpreted in totally human terms. Many of those who hear him in the Nazareth synagogue demand testily: ‘ is he not the carpenter, the Son of Mary?’ (Mark 6: 3). Other passages suggest that he can be interpreted as a heavenly being who for a brief period appears as a ‘ guest’ on earth.
Ephesus, Chalcedon, and Beyond
Authors: Gerald O’Collins S J
Published: November 2023

There was equal danger in believing the Lord Jesus Christ to be God only and not man also, or man only and not God. (St Leo the Great, Tome) Differences between what have been called the ‘ schools’ of Antioch and Alexandria set the stage for the christological controversies of the fifth century and beyond. Unlike the followers of Arius and Apollinarius, the groups who remained unreconciled to the teaching at Ephesus in 431 and Chalcedon in 451 still have their followers— known, respectively, as the Nestorians (who call themselves ‘ Assyrians’ or ‘ the Church of the East’ ) and Monophysites (now generally called ‘ Oriental Orthodox’ ).
Divine and Human
Authors: Gerald O’Collins S J
Published: November 2023

And is it true? And is it true This most tremendous tale of all. The Maker of the stars and sea Become a Child on earth for me? (John Betjeman, ‘ Christmas’ ) Earlier chapters have documented, from the New Testament to date, those Christian beliefs in Jesus Christ which bear on his being (1) divine and human, (2) an eternally pre-existent, divine person, and (3) the Saviour of the whole world. The foundations for such beliefs about this identity-in-relationship with God and the role for human salvation are found in his life, death, and resurrection (with the coming of the Holy Spirit). We have looked at various struggles to maintain intact these beliefs and to clarify them, to the extent that clarification is possible. Contemporary journals and books over flow with systematic questions that could be faced here.
Faith, Holiness, and Virginal Conception
Authors: Gerald O’Collins S J
Published: November 2023

Praising is all a poet understands, The only giving is with empty hands.

(Peter Steele, ‘ XXI’ ) We might begin by going back to the mystics; if there is some guidance to Jesus’ mind in their experience, we can profitably consult St Teresa of Avila on the difficulty she had in expressing what she received from God.(Frederick Crowe, ‘ The Mind of Jesus’ ) Previous chapters have often operated at the interface between exegesis and theology. This will also hold true of this chapter, which takes up two questions which bear on Jesus’ historical life after he came to ‘ the age of reason’ (his faith and holiness) and one which bears on his human origin (the virginal conception).
Introduction
Authors: Moore Brian C J , Tyler, Lorraine K , Marslen-Wilson William
Published: November 2023

Spoken-language communication is arguably the most important activity that distinguishes humans from non-human species. This chapter provides an overview of the chapters that make up this volume on the processes underlying speech communication. The volume includes contributions from researchers with a wide range of specialities within the general area of speech perception and language processing. It also includes contributions from key researchers in neuroanatomy and functional neuroimaging—in an effort to cut across traditional disciplinary boundaries and foster cross-disciplinary interactions in this important and rapidly developing area of the biological and cognitive sciences.
Neural correlates of Early Stone Age tool making: technology, language and cognition in human evolution
Authors: Stout Dietrich , Toth Nicholas , Schick Kathy , Chaminade Thierry
Published: November 2023

Human brains and technology have been coevolving for at least the past 2.6 Myr since the appearance of the first intentionally modified stone tools (Semaw et al. 1997). Roughly 90% of this time span, from 2.6 to 0.25 Myr ago, is encompassed by the Early Stone Age (ESA; generally known outside Africa as the Lower Palaeolithic). This period witnessed a technological progression from simple ‘Oldowan’ stone chips to skilfully shaped ‘Acheulean’ cutting tools, as well as a nearly threefold increase in hominin brain size (figure 1.1).
Wild agency: nested intentionalities in cognitive neuroscience and archaeology
Authors: Jordan J Scott
Published: November 2023

What Malafouris seems to be after in this quotation is a rethinking of the relationship between cognitive science and archaeology, specifically as regards the manner in which we conceptualize cognition and the impact that conceptualization has on our interpretation of archaeological data. In modern taxonomies, cognition is conceptualized as an internal, centralized decision-making function that uses perceptual input in order to generate the appropriate behavioural output (Clark 1997, 2001; Jordan 2003a, 2004). Within the frame-work of such internalism, the archaeological record is conceptualized as constituting a ‘result’ of cognition.
Social cognition
Authors: Frith Chris D
Published: November 2023

As currently used, the term ‘cognition’ refers to the many different processes by which creatures understand and make sense of the world. The term does much the same work as was previously done by the term ‘information processing’ and is strongly influenced by developments in computing beginning in the 1940s. Perception, attention, memory and action planning would all be examples of cognitive processes. All these processes are important in social interactions and the study of information processing in a social setting is referred to as social cognition.
Introduction to Metric and Topological Spaces
Authors: Sutherland Wilson A
Published: November 2023

One of the ways in which topology has influenced other branches of mathematics in the past few decades is by putting the study of continuity and convergence into a general setting. This new edition of Wilson Sutherland's classic text introduces metric and topological spaces by describing some of that influence. The aim is to move gradually from familiar real analysis to abstract topological spaces, using metric spaces as a bridge between the two. The language of metric and topological spaces is established with continuity as the motivating concept. Several concepts are introduced, first in metric spaces and then repeated for topological spaces, to help convey familiarity. The discussion develops to cover connectedness, compactness and completeness, a trio widely used in the rest of mathematics. Topology also has a more geometric aspect which is familiar in popular expositions of the subject as `rubber-sheet geometry', with pictures of Möbius bands, doughnuts, Klein bottles and the like; this geometric aspect is illustrated by describing some standard surfaces, and it is shown how all this fits into the same story as the more analytic developments. The book is primarily aimed at second- or third-year mathematics students. There are numerous exercises, many of the more challenging ones accompanied by hints, as well as a companion website, with further explanations and examples as well as material supplementary to that in the book.
Semiconductor field effect devices
Authors: Winquist Fredrik , Danielsson Bengt
Published: November 2023

The research and development of biosensors is at present in a rapidly growing phase due to the demands from a number of different areas such as clinical chemistry, process industry, agriculture and environmental control. Many different types of biosensor have been developed, and the majority of the biosensor concepts are based on the combination of immobilized enzymes with classical sensors such as photometers, amperometric or potentiometric electrodes, gas electrodes or thermistors. The performance of a biosensor is to a large extent dependent on the sensor elements. One class of sensors that has been developed during the last decade is the solid state chemical sensors; these have properties that make them especially valuable for biosensing purposes. Based on semiconductor technology, they are characterized by their ruggedness, ability to be directly integrated with microelectronics and hence the possibility to be mass fabricated at low cost. One type of such sensor is based on field effect devices, made by the MOS (Metal Oxide Semiconductor) technology. They can be designed either as capacitors or field effect transistors.
Thermometric sensors
Authors: Danielsson Bengt , Winquist Fredrik
Published: November 2023

Bioanalytical calorimetry has many attractive features, which were recognized early in studies using conventional calorimeters. Since biological reactions are usually more or less exothermic, calorimetry offers a general detection method which is insensitive to the optical properties of the sample. Enzymic reactions are associated with rather high molar enthalpy changes in the range of20-100 kJ mol-1 (Table 1) and it is often possible to base measurements on only one enzymic step. This is in contrast to other techniques where the detection is based on, for instance, the change in concentration of coloured reactants. In such cases it is usually necessary to couple the primary reaction with one or several (enzymic) reactions in order to obtain measurable changes.
Cellular assays for lymphoid immune deficiency
Authors: Chapel H , Sewell H
Published: November 2023

Cellular assays for immune deficiency include enumeration of the various cell types involved in the immune response as well as demonstration of their functional abilities. Cellular assays for lymphoid immune deficiency currently involve those of T-cells and B-cells, as well as subpopulations of these cells; in the future, assays for antigen processing cells may also be available. Assays for non specific immune deficiency, i.e. those defects involving phagocytic cells and complement are described in Chapters 3 and 4 respectively.
Neutrophil function tests in clinical immunology
Authors: Gentle T A , Thompson R A
Published: November 2023

Tests of neutrophil function are used in the assessment of suspected immunodeficiency. The types of clinical presentation are often characteristic and the history suggests the need for assessment of neutrophil function. Patients tend to get recurrent staphylococcal infections especially skin infections, and have chronic gingivitis.
Molecular characterization of viral infections in vivo
Authors: Ian Lipkin W , Oldstone Michael B A
Published: November 2023

Natural and experimental infections of animals continue to be important as models in studying the pathogenesis and management of infectious diseases. Classically, methods for examining animal models have required extraction of individual tissues for biochemical or histological analysis. Examples of these techniques reviewed elsewhere in this volume include nucleic acid and protein electrophoresis, immunohistochemistry and enzyme linked immunoadsorbent assays (ELISA). Over the past few years, however, we have used a new technology which allows for sensitive and specific detection of nucleic acids and proteins in whole animal sections (WAS) fixed to tape or artificial membranes. The power of WAS technology rests in its unique potential for defining and quantitating the distribution of genes and gene products in an anatomical context. Further, because the entire animal is examined, there is no bias a priori against recognizing novel distributions of genes or gene products. Although we have used WAS primarily for studies in viral pathogenesis, problems in developmental biology, neoplasia, and pharmacology may also be suitable for WAS analysis. WAS would also seem ideal for the investigation of tissue-specific distributions of transcripts and proteins in transgenic animal systems. In this chapter we will discuss our methods for WAS in situ hybridization and protein blotting (Figure 1 ). For illustrations of WAS applications the reader is referred to a recent review (1 ).
Whole-cell voltage-clamp techniques applied to the study of synaptic function in hippocampal slices
Authors: Madison Daniel V
Published: November 2023

When the technique of recording from brain slices came into general use for electrophysiological experiments, a great many predictions were made about the utility of this preparation for conducting experiments on the physiology and pharmacology of the central nervous system. These predictions were based on some substantial and obvious benefits offered by this preparation. Indeed, the slice preparation has been used for experiments that are difficult or imposible to conduct on in vivo preparations. However, as is often the case when foretelling the future, the predictions on the usefulness of the slice preparation proved inaccurate. Indeed, the brain slice preparation has fulfilled its promise perhaps more than anyone could have imagined.
Optical techniques and Ca2+ imaging
Authors: Moreton R B
Published: November 2023

Optical techniques covers a wide range of subjects, including the use of stains or fluorescent dyes to visualize specific subcellular components, and the use of sophisticated image-analysis techniques to identify and map structures in two or three dimensions, or to study cell motility. This chapter concentrates on the use of computer-linked video cameras to capture and analyse optical information. Specific attention is paid to using fluorescent probes to detect and map the intracellular distribution of ions and molecules, especially that of calcium which is providing so much exciting new information about the way in which receptors are used to translate extracellular signals into control of cell metabolism and secretion. For reviews of some other optical techniques, see refs 1-3.
X-ray Microanalysis
Authors: Wendt-Gallitelli Maria Fiora , Isenberg Gerrit
Published: November 2023

1. Introduction The heart ventricular myocyte is one of those contractile cells where movements of Ca couple excitation to contraction, rhythmically every second. According to our textbooks, it is the Ca bound to troponin C (TnC) that controls the actin-myosin interaction (attachment of cross-bridges). Quantitation of this activator Ca, therefore, would help in understanding the way of contractile activation. Besides knowledge of the concentration of Ca-TnC as a function of time, one should know how and from where the activator Ca derives, and how and to where it is redistributed. During the last two decades, a variety of different methods has addressed the above question. The outcome can be summarized in the simplified model of Figure 1. For mammalian ventricular myocytes, the model postulates most of the activator Ca to derive from an intracellular ‘release compartment’ (R) where it has been stored during diastole. Ca-release is induced by Ca-entry during excitation. Ca diffuses from the release compartment into the myofibrillar space along a gradient. Ca diffusion occurs with Ca binding to TnC. TnC competes with sites on the SR Ca-pump which have an even higher Ca affinity. Thus, after a while, Ca has sequestered out of the myofibrillar space into the ‘uptake compartment’ (U). Ca-influx through the sarcolemma is thought not only to trigger SR Ca-release but also to fill the SR with Ca. Vice versa, not all of the released Ca recirculates to the SR, a fraction of 20% might be extruded into the extracellular space. At steady-state beating, the sum of Ca-influx and Ca-efflux should equal.
Ca2+ Buffering: Computer Programs and Simulations
Authors: Fabiato Alexandre
Published: November 2023

1. Introduction The free calcium concentration ([free Ca24]) inside most animal cells is in the nanomolar (nM) to micromolar (µM) range. When one wants to make up a solution simulating the intracellular milieu, it is not possible to obtain such a low [free Ca24) by simply adding a small amount of calcium to the solution.* In fact, the total calcium contamination of the other salts contained in the solution would be in excess to the [free Ca24) that should be obtained. Thus, it is necessary to use Ca24 buffers that are made of a ligand in equilibrium with a metal, which in this case is Ca24.
Use of Fluorescent Tnc Derivatives and ‘Caged’ Compounds to Study Cellular Ca2+ Phenomena
Authors: Ashley C C , Griffiths P J , Lea T J , Mulligan P , Palmer, R E , Simnett Sarah J
Published: November 2023

1. Stncdanz as an indicator 1.2 Introduction Although it has been established using the photoprotein aequorin (Figure 1) that the free calcium concentration within muscle cells changes rapidly upon activation (1, 2) little is known of the time-course of calcium bound to the contractile system as a result of this transient change in the free calcium.
The Ca2+-Atpase of the Plasma Membrane
Authors: Carafoli Ernesto
Published: November 2023

1. Introduction The ejection of Ca2+ from cells is a necessity dictated by the existence in the plasma membrane of Ca channels which permit, albeit in a strictly controlled fashion, the penetration of Ca into the cell. Normally, Ca is about 10 000 times less concentrated in the cytosol than in the environment: therefore its ejection is an active process, and is indeed mediated by an ATP-powered pump. The pump was discovered by Schatzmann in 1966 in erythrocytes (1), and was subsequently found in a number of other eukaryotic plasma membranes (for reviews, see refs 2-5). The pump belongs to the P-class of ion-motive ATPases (6-7) and is now well-characterized functionally. More recent work on the purified pump has provided significant information on its structural properties (8).
Proteins Involved in the Uptake and Release of Ca2+ from the Sarcoplasmic Reticulum
Authors: Hamilton Susan L , Tate Charlotte A
Published: November 2023

1. Introduction Changes in the intracellular concentration of Ca2+ in skeletal muscle regulate the state of the muscle contraction and relaxation. A number of different proteins located in the sarcoplasmic reticulum (SR) are involved in the regulation of the Ca2+concentrations; some of the proteins with known roles and others with putative roles are listed in Table 1. In this chapter we will detail some of the methods used to study the two proteins most directly involved in controlling Ca2+ levels in skeletal muscle: (a) the Ca2+ ATPase, the protein responsible for the uptake of Ca2+ into the lumen of the SR, and (b) the Ca2+-release channel, the protein responsible for the release of the luminally sequestered Ca2+ into the cytoplasm.
The Role and Study of Mammalian
Authors: McCormack James G , Crompton Martin
Published: November 2023

The inner membrane of mitochondria of mammalian, and perhaps of all vertebrate, tissues contains Ca2+ transport systems that mediate continuous Ca2+ cycling across the membrane (Figure I; see refs 1-3 for reviews). The cycle comprises a Ca2+ uniporter which allows passive Ca2+ entry down the Ca2+ electrochemical gradient and one, or possibly two, active egress mechanisms. The principal efflux mechanism involves obligatory exchange between Ca2+ and Na+ with the probable stoichiometry of 2Na+: 1Ca2\ this exchange is linked to the chemiosmotic H+ circuit via Na+:H+ exchange. Mitochondria may also contain a Na+-independent mechanism for Ca2+ efflux, although whether this involves direct Ca2+: H+ exchange is controversial. Although cycling of Ca2+involves the dissipation of the protonmotive gradient, under normal cellular conditions the calculated overall energy cost is less than 1% of the respiratory capacity of the mitochondria (1, 2).
An enzymatic method for the complete mutagenesis of genes
Authors: Knowles Jonathan , Lehtovaara Päiyi
Published: November 2023

Site-directed mutagenesis has contributed considerably to our understanding of the relationship between protein structure and function. However, since site-directed mutagenesis is laborious, at least with regard to all the possible mutants that should be examined for a full understanding of any particular aspect, it is important that other more efficient methods for the investigation of protein structure by mutagenesis should be available. More importantly. site directed mutagenesis experiments are limited by the imagination of the investigator which has proved in recent years to be often too limited to understand the complexities of proteins.
Spiked oligonucleotide mutagenesis
Authors: Blacklow Stephen C , Knowles Jeremy R
Published: November 2023

Two approaches exist for the mutagenesis of cloned genes. In site-specific mutagenesis the presumed importance of a single amino acid is probed by changing or deleting it and examining the functional consequences. This approach is often helpful in providing experimental evidence for mechanistic suggestions developed from structural and kinetic studies. Random mutagenesis, on the other hand, does not rely on any preconceived notions based on structure or mechanism, but rather is employed to identify all possible changes that satisfy a particular functional selection. These two approaches are therefore complementary and both have been used in this laboratory for studies of structure function relationships in the glycolytic enzyme triosephosphate isomerase. In this chapter we describe a method for the random mutagenesis of any gene that has been cloned and expressed in Escherichia coli. Several different methods have been devised for the random mutagenesis of cloned genes (1). These include in vivo methods such as the use of mutator strains, in vitro enzyme-dependent approaches (e.g. ref. 2, and Chapter 8), and procedures that use chemicals to damage the DNA (e.g. ref. 3, and Chapter 7). However, it is known that mutagenesis by these procedures may result in an uneven distribution of mutations because of the presence of mutagenic ‘hot spots’ in the DNA. The method described in this chapter was developed to ensure complete randomness in the changes of nucleotides in the gene of interest.
Composites
Authors: Vincent Julian F V
Published: November 2023

Composite materials are composed of stiff strong fibres, plates, or particles (the discontinuous phase) in a relatively compliant matrix (the continuous phase). Composites with ceramic materials (CaCO3, hydroxyapatite, etc.) as the discontinuous phase are covered in Chapter 3. In other biological compo sites the discontinuous phase can be protein (as in skin and keratin) or polysaccharide (arthropod cuticle, plants). The chemical nature is not impor tant for mechanical analysis although bond energy and density are important. In order to provide reinforcement, the fibres have to be sufficiently long: maximum reinforcement is obtained with infinitely long fibres; collagen fibres in echinoderms have an aspect ratio of over 5000. The fibre takes forces from the matrix through shear forces developed at the fibre-matrix interface. This transfer of force occurs along a length of fibre determined by the relative moduli of matrix and fibre, the conditions at the interface, and the diameter of the fibre. In order to reinforce effectively, the length of the fibre has to be at least twice this transfer length. At lesser lengths the fibres reinforce less effectively, acting as filler particles. The aim in testing composite materials should be to integrate the morphology of the material (such as the amount, aspect ratio, and orientation of fibres) with the mechanical properties of the whole material and of the separate phases. Harris (1) and Piggott (2) are good introductions to definitions and analysis. Although not strictly composites, cellular materials have been included in this chapter because they are often constructed of composite materials (3).
Cartilage and joints
Authors: Smeathers J E
Published: November 2023

Cartilage is found in various forms in most invertebrates (Coelenterata, Annelida, Mollusca, and Arthropoda) and vertebrates; the literature on cartilage from a wide range of species has been comprehensively reviewed (1). It has been most thoroughly described for the vertebrates, hence this text refers exclusively to mammalian cartilage, the majority of experimental work having been done on human articular cartilage (2). Cartilage is the primary connective tissue of chordates. It can be modified into a variety of forms to produce a flexible coupling between bones and skeletal supporting structures. Vertebrae can move slightly because the fibrocartilagenous discs can bend, twist, and shear. The ends of long bones are coated with articular cartilage, which is very smooth and, when wetted with synovial fluid, allows the bones to slide easily over each other. Cartilage contains cells (chondrocytes) which produce a soft chondromucoid ground substance reinforced with collagen fibre network which can be considered as a composite material, exhibiting rubber-like properties.
Soft composites
Authors: Shadwick Robert E
Published: November 2023

This chapter describes common techniques for characterizing the mechanical properties of soft biological materials in vitro. The important factors to consider when designing an experiment are:
Preparation and Handling of Biological Macromolecules for Crystallization
Authors: Lorber B , Giege R
Published: November 2023

In the crystallization of biological macromolecules the quality and quantity of the required material is important. Although experimenters may have no choice, difficulties in crystal growth may be linked to the nature or source of the biological material. Purification, stabilization, storage, and handling of macromolecules are therefore essential steps prior to crystallization. As a general rule purity and homogeneity are regarded as conditions sine qua non; however. quality of the macromolecules will depend upon the way they are prepared. Although some structures were solved with less than 1 mg of material (for example, ref. !), a few milligrams should be available for the first crystallization trials. Once crystals can be produced which are suitable for X-ray analysis, additional material will be needed to improve their quality and size and to prepare heavy-atom derivatives. For these reasons it is essential that isolation procedures arc able to supply enough fresh macro molecules of reproducible quality.