bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating a Community
Authors: Sharples Niall
Published: November 2020

In the summer of 1979, when I was working on my undergraduate dissertation in the National Museum, I became involved in an interesting piece of field-work that has direct relevance to the material that we are going to examine in this chapter. A Mrs MacDonald came into the museum to enquire whether some objects she had in her possession were of any archaeological significance. She had been encouraged to make this visit by a recent television programme where the presenter discussed and exhibited objects that were similar to those in her possession. She explained to the curator that the objects had been found by a family member during ploughing and had been kept in the kitchen drawer for the last two decades, though they were often brought out for the children to play with. She then removed, from her shopping bag, a gold bracelet and a gold ‘dress fastener’ of distinctive Late Bronze Age type. This had the immediate effect of rendering the museum curator speechless—these were in the days before metal detecting had become a popular hobby, and new finds of this significance were seldom made. The most recent discovery of comparable objects was in the nineteenth century. Further discussion of the nature of the discovery revealed that the location of the find was still remembered; it was just behind the farmhouse. It was also thought that other objects were discovered at the time, but these were discarded, as they were not so interesting. As there was a possibility that objects were still present in the field it was decided that a team would be sent by the museum to explore the finds location. I was dispatched, with two other students then working in the museum, and a metal detector, purchased specially for the occasion, to see what we could find. I have to say that metal detecting must be one of the most boring pastimes ever invented. In our youthful enthusiasm, we decided to be thorough and systematic. We set out a grid that covered the area where the gold had been discovered and began work.
Focused history taking
Authors: Zengeya Stanley Tamuka , Serane Tiroumourougane V
Published: November 2020

Focused history taking is a vital part of the MRCPCH clinical exam; candidates are expected to grasp the key issues and formulate an effective management plan. This station requires candidates to be efficient, purposeful, and well-directed in their approach. The candidate is expected to obtain and present the key facts in the history and suggest an appropriate management plan. The examiner sits in the room as an observer while the candidate takes the history. This gives the examiner ample opportunity to assess the candidate’s communication skills, general approach, and knowledge of the condition. Only 13 minutes are allowed with the patient in the presence of the examiner. In the subsequent 9 minutes, the candidate will present and discuss the history. Problem-oriented history and management is the most effective way of approaching this station. The objectives of obtaining a focused paediatric history are: • to establish and maintain rapport with the child and parents • to obtain an overview of the child’s previous and current health issues • to establish the psychological, family, and social context of a child’s illness • to reach a correct diagnosis (or form a differential diagnosis) • to plan an appropriate management strategy. Although the principles of history taking in children are similar to those used for adults, there are important differences in the scheme and the details. The paediatric case history is potentially more difficult to elicit and is influenced by the age of the child. For each age group, you will have to adapt your style. The primary historian may be the child or another person, usually the parent. The consultation itself is triadic, involving the child, their family (or caregiver), and the doctor. Always keep in mind the principles of communication (discussed in chapter 2) and use an empathic approach while taking the history. Although in most cases the parents give the history, the child must also be encouraged to speak. In young children who have limited speech, you must take the history through the parents or the carers. In teenagers, there is a difficult line to tread between giving the child complete autonomy and allowing the parent to be the main historian.
Examination of the abdomen
Authors: Zengeya Stanley Tamuka , Serane Tiroumourougane V
Published: November 2020

The examination of the abdomen is one of the easier cases in the clinical exam. It is, however, easy for candidates to fail this station if they cannot elicit the appropriate physical findings. As always, listen carefully to the examiner’s instructions. You may be asked to examine either the gastrointestinal system or only the abdomen; they are not the same. Occasionally, you may be instructed to palpate the abdomen and beginning at the hands in such situations will annoy the examiner. While giving instructions to the child, you must use simple language that can be easily understood. The examination of the abdomen is best done in correlation with the available medical history, as it often gives major clues. It helps to have a systematic approach to presenting your findings, which should be practised thoroughly. However, the examination process itself can be performed in a different sequence depending on the age of the child and their degree of cooperation. Key competence skills required in the examination of the abdomen are given in table 7.1. Abdominal cases commonly encountered in the MRCPCH Clinical Exam are listed in table 7.2. These are repeated in every system to reiterate their importance and to help you recollect the initial approach of any clinical exam. Also refer to chapter 4. • On entering the examination room, demonstrate your adherence to infection control measures by washing your hands or decontaminating them using alcohol rub. • Introduce yourself both to the parents and the child. • Talk slowly and clearly with a smile on your face. • Establish rapport with the child and parents (remember that ignoring the child can have negative consequences!). • Ensure privacy: to expose the abdomen adequately, the child should be undressed to the waist. Be careful when exposing older children and adolescents, with whom limited exposure should be practised. Cover the lower part of the body with a bed sheet, to avoid accidental exposure. • Positioning: initial inspection may be done in the standing position. Growth, nutrition, hernias, and abdominal distension are best evaluated in this position.
Indigeneity of Past Landscape Transformations of the Tropics
Authors: Balée William
Published: November 2020

Indigeneity is the living heritage of traditional peoples. It includes not only their languages and cultures but their transformational etchings on landscapes—not just alterations in the form of inanimate structural changes of the substrate, as in the construction of earthworks and edifices, but sometimes changing the composition of the living flora and fauna. Archaeology is crucial to the identification of indigeneity in the past and in the analysis of landscapes and seascapes associated with it. Landscape transformations, from the perspective of historical ecology, refer to the turnover in species of given locales because of human-mediated disturbance. Primary landscape transformation denotes complete species turnover, whereas secondary landscape transformation denotes partial species turnover. In both cases, substrate alterations occur, but in primary landscape transformation these are qualitatively more profound. In order to understand landscape transformations, we might begin with consideration of geographer Carl Sauer’s comment (1963 [1925]: 333) that ‘We cannot form an idea of landscape except in terms of its time relations as well as of its space relations. It is in continuous process of development or of dissolution and replacement.’ Indigeneity is one of the factors involved in dissolution and replacement, which I refer to as ‘transformation’. Landscapes created in the past through mechanisms rooted in indigeneity are often called the ‘built environment’ by archaeologists. In many tropical forests, including those of Greater Amazonia, the Atlantic Coastal Forest, West Africa, Central Africa, Malesia, and Micronesia, both primary and secondary landscape transformations have noticeably affected the distribution of plant and animal species. In some cases, with specific reference to primary landscape transformation, entire forests came into existence, such as in the Llanos de Mojos, Bolivia and in Guinea, West Africa (see Fairhead, Chapter 16 this volume for more detailed discussion of anthropogenic forests in West Africa). Secondary landscape transformation occurred in the context of ancient settlements, the alteration of ridge tops, swidden cultivation, and resource management, such as in Pre-Amazonian forests of Eastern Brazil, Central African forests, and various forests of Malesia.
From Ecological Constraints To Cultural Identities: Pre-Columbian Attitudes toward Food
Authors: Chevalier Alexandre
Published: November 2020

In archaeology, differences of plant remains between contexts, regions or periods are usually interpreted in terms of social inequality (Bender 1978; van der Veen 2003), political power (Hastorf 1993; Quilter and Stocker 1983), territory exploitation (Rosenberg 1990) and, lately, feasting activities (Dietler and Hayden 2001; Duncan et al. 2009; Hastorf 2003), but rarely in terms of group identification, despite the fact that anthropology has highlighted more than once that food expresses one’s identity better than any material culture (Counihan and Kaplan 1998; Fischler 1985; MacClancy 2004; Montanari 2000; Scholliers 2001). In a comparable way to the faunal exploitation strategies discussed by Fiore et al. in the previous chapter, we propose here that plant exploitation strategies relate not only to factors such as optimality or expediency but also to group identity. Based on models drawn from the anthropology of food (Counihan and Van Esterik 1997; Douglas 1971; Fischler 1988; Goody 1982; Lévi-Strauss 1964, 1997; Mead 1997; Mennell et al. 1992; Mintz 1996) and social psychology of intergroup relations (Tajfel and Turner 1979, 1986), as well as on ethnobotanical examples (Pieroni and Price 2006a), we argue that cultural groups produce, select, and eat different food, and therefore exploit different territories, in order to differentiate themselves from other groups and to build strong group identities. In addition to economic rationality, ecological constraints, or technical limitations, social group alimentary choices may also reflect the need to express positive differentiation from an external group and similarity with those from the same group. Appealing to psychological theories of social identification that explain how individuals’ behaviours are affected by their relationships within their groups, we seek to explain how food choices as an expression of group identity may have shaped environments, created long-distance trade, and in some cases led to environmental overexploitation. In this way social identity concepts (Tajfel and Turner 1979, 1986) can help us to understand the link between trade, exotic products, prestige, and identity and the pivotal role plants may have played in the creation of group identity and in defining intergroup relations.
Effects of Ocean Acidification on the Marine Source of Atmospherically Active Trace Gases
Authors: Hopkins Frances , Nightingale Philip
Published: November 2020

A wide range of trace gases, including dimethyl sulphide (DMS) and organohalogens, are formed in the surface oceans via biological and/or photochemical processes. Consequently, these gases become supersaturated in seawater relative to the overlying marine air, leading to a net flux to the atmosphere. Upon entering the atmosphere, they are subject to rapid oxidation or radical attack to produce highly reactive radical species which are involved in a number of important atmospheric and climatic processes. Organohalogens can affect the oxidizing capacity of the atmosphere by interacting with ozone, with implications for air quality, stratospheric ozone levels, and global radiative forcing. DMS and iodine-containing organohalogens (iodocarbons) can both contribute to direct and indirect impacts of aerosols on climate through the production of new particles and cloud condensation nuclei (CCN) in the clean marine atmosphere. Therefore, marine trace gases are considered a vital component of the earth’s climate system, and changes in the net production rate and subsequent sea-to-air flux could have an impact on globally important processes. In recent years, attention has turned to the impact that future ocean acidification may have on the production of such gases, with the greatest focus on DMS and organohalogens. In this chapter, the current state-of-the-art in this growing area of research is outlined. The oceans are a major source of sulphur (S), an element essential to all life, and marine emissions of the gas DMS (chemical formula (CH3)2S) represent a key pathway in the global biogeochemical sulphur cycle. The surface oceans are supersaturated with DMS relative to the atmosphere, resulting in a oneway flux from sea to air (Lovelock et al. 1972; Watson and Liss 1998). DMS is a breakdown product of the biogenically produced dimethyl sulphoniopropionate (DMSP): . . . (CH3)2S+CH2CH2COO- → (CH3)2S + CH2CHCOOH (acrylic acid) (11.1) . . . Single-celled marine phytoplankton are the chief producers of DMSP, and this reaction is catalysed intra- and extracellularly by the enzyme DMSP-lyase (Malin et al. 1992; Liss et al. 1997). The capacity of phytoplankton to produce DMSP varies between species, with prymnesiophytes considered to be the most prolific (Malin et al. 1992 ; Liss et al. 1997 ; Watson and Liss 1998).
The Ice Returns
Authors: Zalasiewicz Jan , Williams Mark
Published: November 2020

Among the marvellous fossils retrieved from Seymour Island—a thin strip of land near the northern tip of the Antarctic Peninsula, is a giant penguin that lived forty million years ago. Called simply ‘Nordenskiöld’s giant penguin’, after one of the great early Antarctic explorers, it is not the kind of animal you would like to meet down a dark alley late at night. Standing at nearly the height of an average man and with a long beak to match, it was much taller than the modern Emperor penguin. Nordenskiöld’s giant penguin was a portent of a cooling climate. Its bones—many of which now reside in the collections of the Natural History Museum in London—have been found within the Eocene mudrocks of Seymour Island. This island holds a special affection for palaeoclimatologists. It was here, in the late nineteenth century, that some of the first Antarctic fossils were found. These give a glimpse of what that continent was like before it became an icy wilderness. Seventy million years ago, wide Cretaceous forests, inhabited by dinosaurs, flourished in Antarctica. Even as little as fifty million years ago, the kinds of tree and shrub that thrive today in Patagonia once covered the hills and slopes of the mountainous Antarctic Peninsula. Their fossilized remains are found in the rocks of Seymour Island. In the summer months the island is warmed by the faint Antarctic sun, its surface melting like a chocolate cake at a picnic. The resulting muddy quagmire is worth persevering with. It yields the most wonderful fossils of ancient plants, among them Auracaria, the warmth-loving monkey-puzzle tree. Antarctic scientists have another, ulterior motive for visiting Seymour Island; those in the know are aware that the Argentine Base at Marambio is famous for its steaks. They are the best on the continent, and everyone hopes to get invited in. How then did Antarctica change from a continent of lush forests to a frozen wasteland? After all, this part of ancient Gondwana had already drifted over the southern polar region during the Cretaceous. Thus, Antarctica is not simply a frozen wasteland because it lies at the Pole.
Electronics and Biological Signal Processing
Authors: Magee Patrick , Tooley Mark
Published: November 2020

This chapter continues the discussion of electricity but looks at the effect of connecting components together and briefly looks at the operational amplifier and active circuits (circuits discussed in the previous chapter have been passive ones, which involve no electronic circuits). It will then describe how the circuits can be used to process biological signals. If a resistor, an inductor and a capacitor are joined as in Figure 5.1, the magnitude of the voltage across the resistor (Vout) will vary as the input frequency, Vin, changes, because of the properties of the capacitor and inductor. The resistive action of inductor and capacitor oppose each other, and at a certain resonant frequency (r in the figure), the total AC resistance (impedance) will be at a minimum. The graph of reactance against frequency demonstrates this, and shows the minimum reactance at the resonant frequency. As the LC and R are forming a voltage divider, the voltage across R will be maximum at this frequency. At other input frequencies, the output voltage will be low. This simple circuit forms the basics of the passive band-pass filter, where the filter passes, or lets through, a certain band of frequencies (around the resonant frequency in this circuit). Frequencies lower or higher than the band-pass will be attenuated. Normally operational amplifiers (discussed in the next section) or digital filters are more effective and are used to achieve the same effect. Resonance is important for the understanding of the behaviour of transducers and this is discussed in Chapter 12. If a square wave is applied to the resistor capacitor network as shown in Figure 5.2, the capacitor charges up on the rising edge of the input with a time constant equal to the product of the resistance (Ω) and the capacitance (F), RC, and the output voltage will be Vouput = Vinput (1 − e−t /RC ). When the square wave is in the off state, or zero volts, the voltage will fall exponentially with the same time constant. It can be seen from the diagram that, with the appropriate values of R and C, the output from the network is a filtered version of the input.
Major Trauma
Authors: Gupta Pawan
Published: November 2020

In the UK, trauma is currently the commonest cause of death in people <40 years and its incidence is predicted to rise over the next 20 years. So you have an important role in the assessment and management of this group of patients. Doctors of the ED perform a vital role in the early stages of management of trauma patients. In patients with multiple injuries, the care is delivered by a trauma team constituted by middle-grade doctors from various specialties. A senior doctor, usually from the ED and with training in dealing with trauma, leads the team. The trauma team is often requested by the prehospital ambulance personnel, but this is not always the case. Although in your first few days you would not be expected to manage such situations on your own, you may come across a patient with serious trauma behind the curtains in a cubicle. Recognizing the seriousness of the situation and calling for help in the form of a trauma team may make all the difference to that patient in terms of recovery. The principles of assessment and management of trauma patients are discussed in the first answer of this chapter. The ATLS course introduces you to the principles of early management of trauma victims and this can be applied to any trauma patient whom you will see in the ED. The skills you learn on the ATLS course are applicable in many situations. It is advisable to attend this training course while you are working in the ED. You should suspect major trauma in the following situations: • Related to vehicles: high-speed collisions, victim’s ejection from the vehicle (partial or total), rollover, prolonged extrication, etc. • Death of a co-passenger • Pedestrians run over or thrown away to a distance, or with a significant impact (>20mph/32kph) • Falls from a height of >6m in adults and >3m in children or two to three times the height of the child. Resuscitation in the first hour in the resuscitation room has been proved to reduce mortality and morbidity among trauma patients, and so it might be you who will have saved the life of an individual.
The development of echocardiography in Sweden
Authors: Persson Stig , Eskilsson Jan
Published: November 2020

Medical history is filled with innovations contributing to the continuous development of medical science, but some achievements may be thought of as real feats. One event which really deserves such a designation should be the introduction of ultrasound in medical diagnosis. This is a real example of creative thinking that cut across scientific borders and which required a lot of careful and time-consuming work with equipment of initially very primitive standards. As described by Håkan westling in the first chapter of this book, it all started in the late 1940s when the young Swedish cardiologist Inge Edler started to take an interest in techniques used during world war II. The account of the very first course of events differ, however, in small details from what I learnt when Edler himself gave me his version. His general aim was to investigate if it would be possible to turn any of the horrors of the war to something positive in the service of mankind. It is true that his first idea was intended for radar and that he got in contact with the physicist Hellmuth Hertz to get advice. when Hertz had judged the idea as unrealistic — the wavelength of radar would not permit a resolution necessary for the visualization of human organs — Edler became interested in the hunt for submarines in the North Sea, where ultrasound was used for detection and as a tool for directing the torpedoes against the right target. Again, he got in touch with Hertz who had recently studied the basics of ultrasound and who immediately realized that it would be a good idea to test it in medical diagnosis. The description of the testing of an ultrasound reflectoscope from Kockum’s shipyard in Malmo, Sweden, in May 1953 and another one from Siemens-Reiniger-werke in west Germany during the autumn of the same year coincides with westling’s report. It is really fascinating to see how human creativity may convert technical equipment originally meant for industrial, non-destructive detection of flaws in materials to the use for diagnosis of defects in the human body.
Ultrasound in vascular disease —state of the art
Authors: Bekelis Kimon , Labropoulos Nicos
Published: November 2020

The current use of ultrasound in vascular disease extends from diagnosis of several disorders to guidance of operative intervention. Duplex ultrasound (DU) is the main diagnostic modality used in patients with carotid disease, deep venous thrombosis (DVT), peripheral arterial disease, monitoring patients with subarachnoid haemorrhage for vasospasm transcranially, and many other routine examinations. The introduction of new technology is permitting the expansion of these applications. New interventions such as carotid stenting and endovascular aneurysm repair have necessitated the use of DU for detecting in-stent restenosis or endoleaks. In preparation for lower extremity bypass, arterial mapping of the lower extremity by DU is used as the sole imaging modality for lower extremity bypass procedures. DU is also used intraoperatively in evaluating carotid endarterectomy, endovenous procedures such as laser and radiofrequency ablation, and the patency of in situ vein bypasses. Most recently, the breakthroughs in bioengineering have resulted in a plethora of applications for vascular ultrasound. Three-dimensional ultrasound has been used in the assessment of carotid plaque volume together with the monitoring of its evolution with time and its response to various treatments. The use of microbubbles as contrast agents during ultrasound imaging allows the assessment of microcirculation and can be used for ultrasound-guided delivery of drugs and genetic therapies. In addition the assessment of brachial flow mediated dilatation and carotid intima–media thickness by DU has provided a non-invasive way of assessing the arterial wall behavior and to evaluate these patients’ risks of adverse cardiovascular events. Finally, the development of intravascular ultrasound has given birth to the field of virtual histology and has opened new frontiers in the measuring intimal thickness and assessing vulnerable plaques. In recent years, the ‘gold standard’ of angiography for arterial mapping of the lower extremities has been challenged by DU. It has been supported as the sole method for evaluating patients undergoing lower extremity interventions by a number of authors. However, scanning the whole arterial tree is time-consuming, and might be obscured in obese patients or patients with tortuous or heavily calcified vessels.
The industrial development of ultrasound —a Swedish perspective
Authors: Arveheim Gunnar
Published: November 2020

My first contact with diagnostic ultrasound was in 1969, when I attended a demonstration of a Siemens Vidoson at Falun hospital, Sweden. A few Vidoson systems were installed in Sweden by the end of the 1960s. I was at that time sales engineer at the Medical Electronics Department at LIC, supplier of products to the public Swedish healthcare system. I joined Roche Bio-Electronics in 1971. There were some early ultrasound products — Fetasonde continuous wave (Cw) Doppler and Arteriosonde blood pressure units made in Cranbury, United States, and a French echoencephaloscope. I visited Lund several times in 1972 and became fascinated by the pioneering ultrasound work performed by Dr Inge Edler. Roche Bio-Electronics was transferred to Kontron, Zürich in 1973. I was entrusted to start up the Swedish subsidiary Kontron AB in February 1973. Bio-Electronics service engineer, Åke Larsén, also accepted the Kontron offer. I decided to focus on ultrasound in 1974, left Kontron, and joined a small trading company, wabloprodukter, as a third part-owner, starting an electromedical department, without salary but 10 % commission on sales. wablo became distributor for Parks Medical Electronics, Oregon, one of the early Doppler manufacturers. Doptone, the first fetal pulsedetector, was released in 1965 by Smith Kline Instruments (SKI), after a technology transfer agreement with Professor Rushmer’s team, headed by Don Baker, Bioengineering Department, University of washington, Seattle. Later, in 1965, Loren Parks released Parks first fetal and vascular Cw Doppler instruments. The two first wablo years became economically tough. I was close to giving up, but made a final week sales trip in southern Sweden in May 1975. On Friday of that week, visiting Allmänna Sjukhuset, Malmö (part of Lund University), Professor Lindell, of the Clinical Physiology Department said: ‘we have tried to find a Parks distributor, so far without success, we need to order two 806 Dopplers’. That became the turning point, and I decided to continue. During the coming years wablo delivered thousands of Parks Dopplers in the Nordic countries. Most of them are still today, 30 + years later, in daily clinical use! At the 2nd European Ultrasound Congress, Munich 1975, the Advanced Diagnostic Research (ADR) booth was crammed.
Mining, Community, and Environment
Authors: O'Brien William
Published: November 2020

The previous chapters in this book have reviewed the extensive research carried out on prehistoric copper mines in Europe. Numerous site investigations provide detailed information on the geological setting of these mines and the types of ore minerals extracted. The same studies yield important insights into methods of rock extraction, ore beneficiation, and smelting, and the overall organization of those activities. Building on this solid base of information, it is possible to move beyond an understanding of mining as a technological process to an emphasis on the prehistoric communities involved. The technical details and logistics of the mining process continue to be important, but are now considered as part of a socially informed chaîne opératoire of early metal production. Mining in the modern era is regarded as an economic activity; however, there is also a distinctive character to the individuals and communities who engage in that work. This is also true of prehistoric mining, which was undertaken within specific historical contexts that were structured by particular sets of cultural values. It was a highly social activity, involving closely-knit groups of individuals working together towards a common purpose, in situations where they depended on each other for their safety. With no written records, the challenge for researchers is to understand these social dynamics using material correlates available in the archaeological record. As in other areas of prehistory, there are certain limits to the inferences that can be made using this type of evidence. That said, the significance of metal to later prehistoric societies provides a broad indication of the importance of mining as an activity. A concern with the social background of these miners goes back to the earliest research in this field. The gradual move towards a ‘social archaeology’ of early copper mining reflects broader paradigm shifts in modern archaeology, away from culture historical explanations to more interpretative understandings of the material record. While recognizing the dangers of cross-cultural generalization, ethnohistoric studies serve to illustrate the vivid social history of mining communities.
Life and Art
Authors: Bradley Richard
Published: November 2020

Not many prehistoric houses survive above their foundations. The three dimensions of the buildings are collapsed (sometimes literally) into the two dimensions of the site plan. That may be all that can be discovered by archaeology, and yet the missing component could have been all-important. The change of perspective is revealing, for the treatment of the walls and roof may be just as significant as the layout of the floor. Few excavated houses are as well preserved as those in the Near East, and there are many parts of Europe in which the question cannot be investigated directly. Here, the existence of ceramic models suggests an alternative approach. During 2010, two exhibitions featuring the arts of the first farmers took place in Britain. They ran simultaneously, one in Oxford and the other in Norwich. They also complemented one another geographically and thematically. The Lost World of Old Europe was organized by The Institute for the Study of the Ancient World at New York University (Anthony 2010), and Unearthed by the Sainsbury Centre for Visual Arts of the University of East Anglia (Bailey et al 2010). The display at the Ashmolean Museum in Oxford featured artefacts from Romania, Moldova, and Bulgaria, whilst that in Norwich was restricted to finds of figurines from Romania, Albania, and Macedonia, although they were compared with others from the Jomon Culture of Japan. Not surprisingly, the Neolithic and Chalcolithic objects spanned a long period of time and were associated with several regional groups. Some were elaborately decorated, while others were entirely plain. The artefacts shown in Norwich were all depictions of the human form, but those in Oxford also included pottery vessels, stone artefacts, and early metalwork. One small group of objects was especially striking, for it consisted of ceramic models of domestic buildings. In one case, from the Cucuteni Culture of Romania, a group of figurines had been discovered inside a miniature house of this kind. The evidence of such models is revealing. There were examples in which the outer wall was highlighted by angular designs, as if to emphasize the rectilinear outline of the building, but there was also a model in the Oxford exhibition which showed a structure with a similar ground plan whose exterior was covered by curvilinear motifs.
The New Order
Authors: Bradley Richard
Published: November 2020

How would someone who had been brought up in a roundhouse adapt to life in a rectangular world? The experience of a servant working for a family in Malawi shows how difficult it could be. Her predicament is described in a book entitled Women’s Work in Heathen Lands, published in 1886. Jan Deregowski quotes the following extract:… In laying the table there is trouble for the girl. At home her house is round; a straight line and the right angle are unknown to her or her parents before her. Day after day therefore she will lay the cloth with the folds anything but parallel with one edge of the table. Plates, knives and forks are set down in a confusing manner, and it is only after lessons often repeated and much annoyance that she begins to see how things might be done (Laws 1886, quoted by Deregowski 1973: 180–1)… That simple story introduces a larger issue. Under what circumstances did people make the transition from a world of circular structures to one of squares and rectangles, and how were their lives affected by that process? It is surprising how much attention had been paid to structural changes among ancient buildings and how little to the political and social circumstances in which they happened. One way of approaching this topic is not only studying the advantages offered by new styles of architecture, but also asking which important features might be lost. That is too rarely considered. Many of the approaches described in Chapter 2 emphasized the possibilities offered by the change from circular to rectangular buildings. Houses could be larger and could accommodate more people; they would be easier to maintain; they could be expanded as the number of inhabitants increased and space was subdivided; in many cases rectilinear dwellings could be inhabited over longer periods than roundhouses. None of those arguments is unsatisfactory in itself, but all are incomplete because they do not take into account the motives of the people who chose to live there. Chapter 2 also showed how houses could be used to emphasize subtle distinctions among their inhabitants: differences that were based on age, gender, and social standing.
Concentration of the extract
Authors: Harris E. L V.
Published: November 2020

A concentration step is frequently required after a clarified solution of the protein has been obtained, in order to aid subsequent purification steps. This is particularly important when the protein is obtained in culture medium from cells (e.g. bacteria or tissue culture cells). Concentration of the protein solution results in a decreased volume, as well as a higher protein concentration. Clearly a smaller volume of solution is easier to handle in subsequent steps, such as precipitation or loading onto a chromatography column. Higher protein concentration minimize protein losses by non-specific adsorption to container walls or column matrices. In addition many subsequent purification steps require a minimum protein concentration to be effective, for example, precipitation is more efficient at concentrations above 100 μg/ml, whilst for adsorption chromatography (e.g. ion exchange or affinity) the concentration of protein must be greater than the dissociation constant. Concentration is achieved by removal of water and other small molecules: (a) By addition of a dry matrix polymer with pores that are too small to allow entry of the large protein molecules (Section 2). (b) By removal of the small molecules through a semi-permeable membrane which will not allow the large molecules through (i.e. ultrafiltration, Section 3). (c) By removal of water in vacua (i.e. lyophilization, Section 4). Precipitation can also be used to concentrate proteins if the pellet is redissolved in a smaller volume, and in addition often results in some degree of purification of the protein of interest. However, as mentioned above precipitation is more effective if the total protein concentration is above 100 μg/ml (see Section 6). Two-phase aqueous extraction can also be used to concentrate the protein, with an associated degree of purification (see Section 7). This is one of the simplest and quickest methods of concentrating solutions of proteins, requiring minimal apparatus. A dry matrix polymer, such as Sephadex, is added to the protein solution and allowed to absorb the water and other small molecules; the pores within the matrix are too small to allow the protein to be absorbed.
Experimental Design, Quantitative Analysis, and the Cartography of Crystal Growth
Authors: Carter C. W.
Published: November 2020

This chapter is about practical uses of mathematical models to simplify the task of finding the best conditions under which to crystallize a macromolecule. The models describe a system’s response to changes in the independent variables under experimental control. Such a mathematical description is a surface, whose two-dimensional projections can be plotted, so it is usually called a ‘response surface’. Various methods have been described for navigating an unknown surface. They share important characteristics: experiments performed at different levels of the independent variables are scored quantitatively, and fitted implicitly or explicitly, to some model for system behaviour. Initially, one examines behaviour on a coarse grid, seeking approximate indications for multiple crystal forms and identifying important experimental variables. Later, individual locations on the surface are mapped in greater detail to optimize conditions. Finding ‘winning combinations’ for crystal growth can be approached successively with increasingly well-defined protocols and with greater confidence. Whether it is used explicitly or more intuitively, the idea of a response surface underlies the experimental investigation of all multivariate processes, like crystal growth, where one hopes to find a ‘best’ set of conditions. The optimization process is illustrated schematically in Figure 1. In general, there are three stages to this quantitative approach: (a) Design. One must first induce variation in some desired experimental result by changing the experimental conditions. Experiments are performed according to a plan or design. Decisions must be made concerning the experimental variables and how to sample them. (b) Experiments and scores. Each experiment provides an estimate for how the system behaves at the corresponding point in the experimental space. When these estimates are examined together as a group, patterns often appear. For example, a crystal polymorphism may occur only in restricted regions of the variable space explored by the experiment. (c) Fitting and testing models. Imposing a mathematical model onto such patterns provides a way to predict how the system will behave at points where there were no experiments. The better the predictions, the better the model. Adequate models provide accurate interpolation within the range of experimental variables originally sampled; occasionally a very good model will correctly predict behaviour outside it (1).
Crystallization of Membrane Proteins
Authors: Reiss-Husson F. , Picot D.
Published: November 2020

Crystallization of membrane proteins is one of the most recent developments in protein crystal growth; in 1980, for the first time, two membrane proteins were successfully crystallized, bacteriorhodopsin (1) and porin (2). Since then, a number of membrane proteins (about 30) yielded three-dimensional crystals. In several cases, the quality of the crystals was sufficient for X-ray diffraction studies. The first atomic structure of a membrane protein, a photosynthetic bacterial reaction centre, was described in 1985 (3), followed by the structure of about ten other membrane protein families. Crystallization of membrane proteins is now an actively growing field, and has been discussed in several recent reviews (4-8). The major difficulty in the study of membrane proteins, which for years hampered their crystallization, comes from their peculiar solubility properties. These originate from their tight association with other membrane components, particularly lipids. Indeed integral membrane proteins contain hydrophobic surface regions buried in the lipid bilayer core, as well as hydrophilic regions with charged or polar residues more or less exposed at the external faces of the membrane. Disruption of the bilayer for isolating a membrane protein can be done in various ways: extraction with organic solvents, use of chaotropic agents, or solubilization by a detergent. The last method is the most frequently used, since it maintains the biological activity of the protein if a suitable detergent is found. This chapter will be restricted to specific aspects of three-dimensional crystallizations done in micellar solutions of detergent. In some cases, it is possible to separate soluble domains from the membrane protein either by limited proteolysis or by genetic engineering. Such protein fragments can then be treated as soluble proteins and so will not be discussed further in this chapter. We refer to Chapter 12 and the review by Kühlbrandt (9) for the methodology of two-dimensional crystallization used for electron diffraction. The general principles discussed in this book for the crystallization of soluble biological macromolecules apply for membrane proteins; the protein solution must be brought to supersaturation by modifying its physical parameters (concentrations of constituents, ionic strength, and so on), so that nucleation may occur.
Basic procedures
Authors: Chan Weng C , White Peter D
Published: November 2020

A number of excellent descriptions of the techniques related to peptide chain assembly have already been published. These processes are also described in the operator manuals supplied by the peptide synthesis instrument manufacturers. Accordingly, the treatment of the subject presented here has been kept brief in order to provide more space in this volume for those topics not covered in detail in other publications of this type. The protocols have been written as they would be carried out using a manual peptide synthesis vessel. Whilst it is appreciated that most scientists preparing peptides will be using automated peptide synthesizers, it is not possible, given the wide variation in operating procedures, to describe how such methods may be applied to individual instruments. Particular emphasis has been given here to those operations which are typically carried out off-instrument, such as first residue attachment and peptide-resin cleavage. The operations described in this chapter can be carried out in a purpose-built peptide synthesis vessel or in a sintered glass funnel fitted with a three-way stopcock. The operation of the system is extremely simple: solvents are added from the top of the vessel, ensuring any resin adhering to the sides is rinsed down into the resin bed; the resin bed is agitated by setting the tap to position 1 to allow flow of nitrogen to the reaction vessel; solvents and reagents are removed by setting the tap to position 2 to connect the vessel to the vacuum. The use of such vessels has previously been described in detail. Peptide synthesis resins are extremely fragile and the beads, if wrongly handled, can easily fracture, leading to the generation of fines which can block reaction vessel filter-frits and solvent lines. It is particularly important that the correct method is used for mixing the resin and soluble reactants. Polystyrene-based supports are best agitated by bubbling an inert gas through the resin bed, or by shaking or vortexing the reaction vessel. Whilst all of these approaches are employed in commercial synthesizers, gas-bubbling and shaking are the most appropriate for use in manual synthesis.
Difficult peptides
Authors: Quibell Martin , Johnson Tony
Published: November 2020

Solid phase peptide synthesis (SPPS), first proposed by R. B. Merrifield in 1962, has evolved over three decades into a tremendously powerful method for the preparation of peptides and small proteins. An absolute prerequisite for successful syntheses in all solid phase schemes is that reactions which accumulate solid supported products, and by the very nature of the technique contaminating by-products, must proceed cleanly and efficiently. During the earlier years of SPPS this optimal situation was not always achieved, primarily due to contaminated reagents and ill-defined polymers in combination with poorly flexible protection strategies. As the methods of SPPS gained popularity and more widespread application, reagents and protection strategies were improved and refined. However, reports of notable successful syntheses were accompanied by then unexplained failures, which have since been collectively termed ‘difficult peptides’. This chapter describes how an intrinsic understanding behind the occurrence of ‘difficult peptides’ has accumulated, leading to a general synthetic solution—the utilization of a backbone amide protection strategy. Within a few years of the introduction of SPPS, it was recognized that the assembly of some peptide sequences posed a special synthetic problem. The main feature evident during these syntheses was a sudden decrease in reaction kinetics, leading to incomplete amino-acylation by activated amino acid residues. The unreacted sites were readily detected by the Kaiser test for free amine; however, couplings showed no significant improvement even upon repeated or prolonged reaction. Efficient reactions are known to occur within a fully solvated peptide-polymer matrix, where reagent penetration is rapid and unhindered. This optimal situation no longer exists during the assembly of a difficult peptide, where the normally accessible solid phase reaction matrix becomes partially inaccessible during assembly. This situation arises suddenly, typically 6-12 residues into the synthesis, and may then persist for a number of cycles before easing, or in extreme cases remain throughout the completion of the assembly. The crude products are particularly poor if slower coupling β-branched residues (isoleucine, valine, threonine) are introduced after the onset of synthetic difficulties. The principles underlying the occurrence of difficult peptide sequences have for many years been the focus of intense debate and research. An intrinsic feature of the numerous ideas proposed is that aggregation occurs resulting in poor solvation within the peptide-polymer matrix.