bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical Aspects and Handling of Macromolecular Solutions and Crystals
Authors: Lorber B. , Giegé R.
Published: November 2020

The quality and quantity of the macromolecular samples are important prerequisites for successful crystallizations. Proteins and nucleic acids extracted from living cells or synthesized in vitro differ from small molecules by additional properties intrinsic to their chemical nature and their larger size. They are frequently difficult to prepare at a high degree of purity and homogeneity. Besides traces of impurities, harsh treatments may decrease their stability and activity through different kinds of alterations. Consequently, the quality of biomacromolecules depends on the way they are prepared and handled. As a general rule purity and homogeneity are regarded as conditions sine qua non. Accordingly, purification, stabilization, storage, and handling of macromolecules are essential steps prior to crystallization attempts. Other difficulties in crystal growth may come from the source of the biological material. It is advisable to have at disposal a few milligrams of material when starting first crystallization trials although structures were solved with submilligram quantities of protein (1). Once crystals suitable for X-ray analysis can be produced, additional material is often needed to improve their quality and size and to prepare heavy-atom derivatives. It is thus essential that isolation procedures are able to supply enough fresh material of reproducible quality. Similar situations are encountered with multi-macromolecular assemblies (e.g. viruses, nucleosomes, ribosomal particles, or their subunits). This chapter discusses biochemical methods used to prepare and characterize macromolecules intended for crystallization assays. Practical aspects concerning manipulation and qualitative analyses of soluble proteins will be emphasized. The cases of nucleic acids and membrane proteins are described in more detail in Chapters 8 and 9. Peculiar aspects of molecular biology that are important for crystallogenesis are presented in Chapter 3. They include the design of engineered macromolecules with new physical properties or modified to simplify purification or crystallographic analysis. Finally, methods for identification of macromolecular content of crystals and measurements of their density are presented as well. Many biological functions are sustained by classes of proteins and nucleic acids universally present in living organisms so that the source of macromolecules may seem unimportant. In fact, better crystallization conditions or better diffracting crystals are frequently found by switching from one organism to another.
Nucleic Acids and Their Complexes
Authors: Dock-Bregeon A.-C. , Moras D.
Published: November 2020

At first glance crystallizing nucleic acids poses the same problems as crystallizing proteins since most of the variables to investigate are alike. It is thus astonishing that crystallization data banks (1) that describe so many successful protein crystallizations are so poor in information on nucleic acids. This relies on the physico-chemical and biochemical characteristics of nucleic acids distinguishing them from proteins. The aim of this chapter is to underline features explaining the difficulties often encountered in nucleic acid crystallization and to discuss strategies that could help to crystallize them more readily, either as free molecules or as complexes with proteins. Other general principles, in particular for RNA crystallization, are discussed in ref. 2. Among natural nucleic acids only the smaller ones provide good candidates for successful crystallizations. Large DNAs or RNAs can a priori be excluded because of their flexibility that generates conformational heterogeneity not compatible with crystallization. Thus the smaller RNAs with more compact structures (with 75-120 nt), especially transfer RNAs (tRNAs), but also 5S RNA, were the first natural nucleic acids to be crystallized (3, 4). At present attempts are being made with other RNA systems, such as ribozymes and introns, fragments of mRNA, viroids, viral and other tRNA-like RNAs, SELEX-evolved RNAs, and crystallization successes leading to X-ray structure determinations were reported for RNA domains of up to 160 nt long, with the resolution of the P4-P6 domain of the self-splicing Tetrahymena intron (5). The recent excitement in nucleic acid crystallography, and particularly in RNA crystallography, have partly been due to technological improvements in the preparation methods of the molecules. Advances in oligonucleotide chemical synthesis provide opportunity for making large amounts of pure desoxyribo- and more recently of ribo-oligomers of any desired sequence. This led to the crystallization of a number of DNA and RNA fragments and was followed by the co-crystallization of complexes between proteins and such synthetic fragments. Transcription methods of RNAs from synthetic DNA templates were also essential for rejuvenating the structural biology of RNAs. In the case of complexes of proteins with RNAs, the main difficulty was to purify large quantities of homogeneous biological material with well defined physico-chemical properties.
From Solution to Crystals With a Physico-Chemical Aspect
Authors: Riès-Kautt M. , Ducruix A.
Published: November 2020

Biological macromolecules follow the same thermodynamic rules as inorganic or organic small molecules concerning supersaturation, nucleation, and crystal growth (1). Nevertheless macromolecules present particularities, because the intramolecular interactions responsible of their tertiary structure, the intermolecular interactions involved in the crystal contacts, and the interactions necessary to solubilize them in a solvent are similar. Therefore these different interactions may become competitive with each other. In addition, the biological properties of biological macromolecules may be conserved although the physico-chemical properties, such as the net charge, may change depending on the crystallization conditions (pH, ionic strength, etc.). A charged biological macromolecule requires counterions to maintain the electroneutrality of the solution; therefore it should be considered as a protein (or nucleic acid) salt with its own physico-chemical properties, depending on the nature of the counterions. To crystallize a biological macromolecule, its solution must have reached supersaturation which is the driving force for crystal growth. The understanding of the influence of the crystallization parameters on protein solubility of model proteins is necessary to guide the preparation of crystals of new proteins and their manipulation. Only the practical issues are developed in this chapter, and the reader should refer to recent reviews (2-4) for a description of the fundamental physical chemistry underlying crystallogenesis. The solubilization of a solute (e.g. a biological macromolecule) in an efficient solvent requires solvent-solute interactions, which must be similar to the solvent-solvent interactions and to the solute-solute interactions of the compound to be dissolved. All of the compounds of a protein solution (protein, water, buffer, crystallizing agents, and others) interact with each other via various, often weak, types of interactions: monopole-monopole, monopole-dipole, dipole-dipole, Van der Waals hydrophobic interactions, and hydrogen bonds. Solubility is defined as the amount of solute dissolved in a solution in equilibrium with its crystal form at a given temperature. For example, crystalline ammonium sulfate dissolves at 25°C until its concentration reaches 4.1 moles per litre of water, the excess remaining non-dissolved. More salt can be dissolved when raising the temperature, but if the temperature is brought back to 25°C, the solution becomes supersaturated, and the excess of salt crystallizes until its concentration reaches again its solubility value at 25°C (4.1 moles per litre of water).
Diagnostic of Pre-Nucleation and Nucleation By Spectroscopic Methods and Background on the Physics of Crystal Growth
Authors: Veesler S. , Boistelle R.
Published: November 2020

Unlike the crystallization of small inorganic molecules, the problem of protein crystallization was first approached by trial and error methods without any theoretical background. A physico-chemical approach was chosen because crystallographers and biochemists needed criteria to rationally select crystallization conditions. In fact, the problem of the production of homogeneous and structurally perfect protein crystals is set the same as the production of high-quality crystals for opto-electronic applications, because, in both cases, the crystal growth mechanisms are the same. Biological macromolecules and small organic molecules follow the same rules concerning crystallization even if each material exhibits specific characteristics. This chapter introduces the fundamentals of crystallization: supersaturation, nucleation, and crystal growth mechanisms. Phase diagrams are presented in Chapter 10. Special attention will be paid to the behaviour of the macromolecules in solution and to the techniques used for their analysis: light scattering (LS), small angle X-ray scattering (SAXS), small angle neutron scattering (SANS), and osmotic pressure (OP). Before obtaining any nucleation or growth, it is necessary to dissolve the biological macromolecules under consideration in some good solvent. However, it may immediately be asked whether a good solvent is a solvent in which the material is highly soluble, or in which nucleation is easily controlled, or in which growth is fast, or solvent in which the crystals exhibit the appropriate morphology. In practice, the choice of the solvent often depends on the nature of the material to be dissolved, taking into account the well known rule which says that ‘like dissolves like’. This means that, for dissolution to occur, it is necessary that the solute and the solvent exchange bonds: between an ion and a dipole, a dipole and another dipole, hydrogen bonds, and/or Van der Waals bonds. Therefore, the nature of the bonds depends on both the nature of the solute and the solvent which can be dipolar protic, dipolar aprotic, or completely apolar. Once the material has dissolved, the solution must be supersaturated in order to observe nucleation or growth. The solution is supersaturated when the solute concentration exceeds its solubility. There are several ways to achieve supersaturation.
Soaking Techniques
Authors: Stum E. A. , Gleichmann T.
Published: November 2020

Once crystals of a macromolecule are obtained there are many circumstances where it is necessary to change the environment in which the macromolecule is bathed. Such changes include the addition of inhibitors, activators, substrates, products, cryo-protectants, and heavy atoms to the bathing solution to achieve their binding to the macromolecule, which may have sufficient freedom to undergo some conformational changes in response to these effectors. In fact, macromolecular crystals have typically a high solvent content which ranges from 27-95% (1, 2). Although, part of this solvent, ‘bound solvent’ (typically 10%) is tightly associated with the protein matrix consisting of both water molecules and other ions that occupy well defined positions in refined crystal structure it can be replaced in soaking experiments, at a slower rate compared to the ‘free solvent’. In this chapter we will consider the relative merits of various methods for modifying crystals, the restraints that the lattice may impose on the macromolecule, and the relative merits of soaking compared to co-crystallization. The size and configuration of the channels within the lattice of macromolecular crystals will determine the maximum size of the solute molecules that may diffuse in. The solvent channels are sufficiently large to allow for the diffusion of most small molecules to any part of the surface of the macromolecule accessible in solution except for the regions involved in crystal contacts, although in some cases lattice forces may hinder conformational changes or rearrangements of the macromolecule in crystal. In other cases, the forces that drive the conformational changes can be sufficient to overcome the constraints imposed by the crystalline lattice leading to the disruption of intermolecular and crystal contacts resulting in the cracking and dissolution of the crystals. Some lattices may be more flexible and capable of accommodating conformational changes, and while crystals may crack initially, they may subsequently anneal into a new rearrangement and occasionally improve their crystallinity. In general small changes are easily accommodated and many macromolecules maintain their activity in the crystalline state. This is exploited in time-resolved crystallography to obtain structural information of transition states of enzymes.
Phosphopeptide synthesis
Authors: White Peter D
Published: November 2020

Protein phosphorylation mediated by protein kinases is the principal mechanism by which eukaryotic cellular processes are modulated by external physiological stimuli. Phosphopeptides are essential tools for the study of this process, serving as model substrates for phosphatases, as antigens for the production of antibodies against phosphorylated proteins, and as reference compounds for determining their physical parameters. The development of methods for the production of phosphopeptides has consequently attracted considerable interest over the last few years, and these endeavours have yielded reliable procedures which have now made their synthesis routine. There are two strategies used currently for the preparation of phosphopeptides: the building block approach, in which pre-formed protected phosphoamino acids are incorporated during the course of chain assembly, and the global phosphorylation method, which involves post-synthetic phosphorylation of serine, threonine, or tyrosine side-chain hydroxyl groups on the solid support. The building block procedure is certainly the more straightforward of the two approaches and has now become, owing to the availability of suitably protected phosphoamino acids, the standard method for the routine production of phosphopeptides. For the side-chain protection of phosphotyrosine in Fmoc/tBu-based solid phase synthesis, methyl, benzyl, t-butyl, dialkylamino, and silyl groups have been employed. Of these, benzyl is most useful as it is the most convenient to introduce and is rapidly removed during the TFA-mediated acidolysis step. Only the mono-benzyl ester, Fmoc-Tyr(PO(OBzl)-OH)-OH 1, is available commercially; the dibenzyl ester offers no practical benefit as it undergoes mono-debenzylation in the course of the piperidine-mediated Fmoc deprotection reaction. Also available commercially is Fmoc-Tyr(PO3H2)-OH 2. This derivative, despite having no phosphate protection, appears to work well, particularly in the synthesis of small- to medium-sized phosphopeptides; although formation of the pyrophosphate 3 can be a problem in peptides containing adjacent Tyr(PO3H2) residues. Phosphate triesters of serine and threonine are not compatible with Fmoc/tBu chemistry as they undergo β-elimination when treated with piperidine, resulting in the formation of dehydroalanine and dehydoaminobutyric acid, respectively For this reason, it was long believed that the building block approach could not be used for preparation of peptides containing these amino acids.
Production of targeted embryonic stem cell clones
Authors: Matise Michael P. , Joyner Alexandra L.
Published: November 2020

The discovery that cloned DNA introduced into tissue culture cells can undergo homologous recombination at specific chromosomal loci has revolutionized our ability to study gene function in cell culture and in vivo. In theory, this technique, termed gene targeting, allows one to generate any type of mutation in any cloned gene. The kinds of mutations that can be created include null mutations, point mutations, deletions of specific functional domains, exchanges of functional domains from related genes, and gain-of-function mutations in which exogenous cDNA sequences are inserted adjacent to endogenous regulatory sequences. In principle, such specific genetic alterations can be made in any cell line growing in culture. However, not all cell types can be maintained in culture under the conditions necessary for transfection and selection. Over ten years ago, pluripotent embryonic stem (ES) cells derived from the inner cell mass (ICM) of mouse blastocyst stage embryos were isolated and conditions defined for their propogation and maintenance in culture (1, 2). ES cells resemble ICM cells in many respects, including their ability to contribute to all embryonic tissues in chimeric mice. Using stringent culture conditions, the embryonic developmental potential of ES cells can be maintained following genetic manipulations and after many passages in vitro. Furthermore, permanent mouse lines carrying genetic alterations introduced into ES cells can be obtained by transmitting the mutation through the germline by generating ES cell chimeras (described in Chapters 4 and 5). Thus, applying gene targeting technology to ES cells in culture affords researchers the opportunity to modify endogenous genes and study their function in vivo. In initial studies, one of the main challenges of gene targeting was to distinguish the rare homologous recombination events from more commonly occurring random integrations (discussed in Chapter 1). However, advances in cell culture and in selection schemes, in vector construction using isogenic DNA, and in the application of rapid screening procedures have made it possible to identify homologous recombination events efficiently. Since there are numerous publications available that describe basic tissue culture techniques in this chapter we will only describe techniques specific for ES cells.
Stopped-flow spectroscopy
Authors: Wilson M. T. , Torres J.
Published: November 2020

There was a time, fortunately some years ago now, when to undertake rapid kinetic measurements using a stopped-flow spectrophotometer verged on the heroic. One needed to be armed with knowledge of amplifiers, light sources, oscilloscopes etc. and ideally one’s credibility was greatly enhanced were one to build one’s own instrument. Analysis of the data was similarly difficult. To obtain a single rate constant might involve a wide range of skills in addition to those required for the chemical/biochemical manipulation of the system and could easily include photography, developing prints and considerable mathematical agility. Now all this has changed and, from the point of view of the scientist attempting to solve problems through transient kinetic studies, a good thing too! Very high quality data can readily be obtained by anyone with a few hours training and the ability to use a mouse and ‘point and click’ programs. Excellent stopped -flow spectrophotometers can be bought which are reliable, stable, sensitive and which are controlled by computers able to signal-average and to analyse, in seconds, kinetic progress curves in a number of ways yielding rate constants, amplitudes, residuals and statistics. Because it is now so easy, from the technical point of view, to make measurement and to do so without an apprenticeship in kinetic methods, it becomes important to make sure that one collects data that are meaningful and open to sensible interpretation. There are a number of pitfalls to avoid. The emphasis of this article is, therefore, somewhat different to that written by Eccleston (1) in an earlier volume of this series. Less time will be spent on consideration of the hardware, although the general principles are given, but the focus will be on making sure that the data collected means what one thinks it means and then how to be sure one is extracting kinetic parameters from this in a sensible way. With the advent of powerful, fast computers it has now become possible to process very large data sets quickly and this has paved the way for the application of ‘rapid scan’ devices (usually, but not exclusively, diode arrays), which allow complete spectra to be collected at very short time intervals during a reaction.
Spectrophotometry and fluorimetry of cellular compartments and Intracellular processes
Authors: Lindsay Bashford C.
Published: November 2020

Optical spectroscopy, Spectrophotometry and fluorimetry can be used to monitor processes occurring in living cells provided that suitable chromophores are present which ‘report’ on the events in which they participate. The advantages of optical techniques are manifold. Firstly they can be fast—with appropriate apparatus events in the pico- and nano-second domains can be studied by fluorescence spectroscopy. Secondly they are continuous—instant feedback from the experimental system can guide the most complex of experimental protocols, and allow the experimenter to adjust system parameters as necessary. Thirdly they are convenient, and most laboratories have access to equipment that can provide quantitative analysis of optical signals; examples include conventional spectrophotometers/fluorimeters, dedicated instruments (e.g. for fluorescence lifetime and polarization measurements), cameras, microscopes and plate readers. Significantly detectors from one apparatus can often be used on others to open up new experimental protocols. Fortunately the principles underlying the use of such a diverse array of optical devices are straightforward and universal—they apply just as much to laboratory ‘work-horse’ instruments as they do to the most specialized, laser-illuminated fluorescence microscope. The availability of fast laboratory computers with large storage capacities means that most modern spectrometers are microprocessor controlled and digitization of signals opens up the full range of possibilities of data accumulation, storage, analysis and interpretation. The main problem with optical measurements is not the acquisition but rather the interpretation of the data obtained. Straightforward analysis of the results depends on the clarity of the experimental design and the appropriate choice of chromophore. This chapter describes some of the problems that can be addressed by spectroscopic techniques and attempts to give guidance on good experimental design. Optical spectroscopy requires either spectrophotometers, to measure absorbance, fluorimeters, to measure fluorescence, or microscopes, which can measure fluorescence or absorbance of single cells or small groups of cells. Fluorimeters and spectrophotometers usually require solutions or suspensions of material in conventional cuvettes; microscopes provide two-dimensional images from smears, slices or surfaces. Other devices that record signals resolved in two-dimensions include gel scanners and microplate readers.
Learn
Authors: Shroff Gautam
Published: November 2020

In February 2011, IBM’s Watson computer entered the championship round of the popular TV quiz show Jeopardy!, going on to beat Brad Rutter and Ken Jennings, each long-time champions of the game. Fourteen years earlier, in 1997, IBM’s Deep Blue computer had beaten world chess champion Garry Kasparov. At that time no one ascribed any aspects of human ‘intelligence’ to Deep Blue, even though playing chess well is often considered an indicator of human intelligence. Deep Blue’s feat, while remarkable, relied on using vast amounts of computing power to look ahead and search through many millions of possible move sequences. ‘Brute force, not “intelligence”,’ we all said. Watson’s success certainly appeared similar. Looking at Watson one saw dozens of servers and many terabytes of memory, packed into ‘the equivalent of eight refrigerators’, to quote Dave Ferrucci, the architect of Watson. Why should Watson be a surprise? Consider one of the easier questions that Watson answered during Jeopardy!: ‘Which New Yorker who fought at the Battle of Gettysburg was once considered the inventor of baseball?’ A quick Google search might reveal that Alexander Cartwright wrote the rules of the game; further, he also lived in Manhattan. But what about having fought at Gettysburg? Adding ‘civil war’ or even ‘Gettysburg’ to the query brings us to a Wikipedia page for Abner Doubleday where we find that he ‘is often mistakenly credited with having invented baseball’. ‘Abner Doubleday ’ is indeed the right answer, which Watson guessed correctly. However, if Watson was following these sequence of steps, just as you or I might, how advanced would its abilities to understand natural language have to be? Notice that it would have had to parse the sentence ‘is often mistakenly credited with . . .’ and ‘understand’ it to a sufficient degree and recognize it as providing sufficient evidence to conclude that Abner Doubleday was ‘once considered the inventor of baseball’. Of course, the questions can be tougher: ‘B.I.D. means you take and Rx this many times a day’—what’s your guess? How is Watson supposed to ‘know’ that ‘B.I.D.’ stands for the Latin bis in die, meaning twice a day, and not for ‘B.I.D. Canada Ltd.’, a manufacturer and installer of bulk handling equipment, or even Bid Rx, an internet website? How does it decide that Rx is also a medical abbreviation? If it had to figure all this out from Wikipedia and other public resources it would certainly need farmore sophisticated techniques for processing language than we have seen in Chapter 2.
Antimony, Gold, and Jupiter's Wolf
Authors: Wothers Peter
Published: November 2020

The iconic Periodic Table of the Elements is now in its most satisfyingly elegant form. This is because all the 'gaps' corresponding to missing elements in the seventh row, or period, have recently been filled and the elements named. But where do these names come from? For some, usually the most recent, the origins are quite obvious, but in others - even well-known elements such as oxygen or nitrogen - the roots are less clear. Here, Peter Wothers explores the fascinating and often surprising stories behind how the chemical elements received their names. Delving back in time to explore the history and gradual development of chemistry, he sifts through medieval manuscripts for clues to the stories surrounding the discovery of the elements, showing how they were first encountered or created, and how they were used in everyday lives. As he reveals, the oldest-known elements were often associated with astronomical bodies, and connections with the heavens influenced the naming of a number of elements. Following this, a number of elements, including hydrogen and oxygen, were named during the great reform of chemistry, set amidst the French Revolution. While some of the origins of the names were controversial (and, indeed incorrect - some saying, for instance, that oxygen might be literally taken to mean 'the son of a vinegar merchant'), they have nonetheless influenced language used around the world to this very day. Throughout, Wothers delights in dusting off the original sources, and bringing to light the astonishing, the unusual, and the downright weird origins behind the names of the elements so familiar to us today.
The Salt Makers
Authors: Wothers Peter
Published: November 2020

This chapter looks at the elements from the penultimate group of the periodic table—the halogens (‘salt-formers’). We shall see that the first of these elements was discovered by Scheele during his investigations of the mineral pyrolusite. Lavoisier knew of the element but he failed to recognize it as such since he was convinced the gas had to contain oxygen and so must be a compound. It was left to Davy to prove that this was not so, which led to the English chemist naming this element that had been discovered (but not properly named) over thirty years before by the great Scheele. Davy’s choice was to influence the names given to all the members of this group, including the most recent member named in 2016. There are three common acids known as mineral acids, since they may all be obtained by heating combinations of certain minerals. Their modern names are nitric acid, sulfuric acid, and hydrochloric acid. Of these three, hydrochloric was probably the last to be discovered. Nitric and sulfuric acids were obtained in the thirteenth or early fourteenth centuries, but the earliest unambiguous preparation of relatively pure hydrochloric acid is from a hundred years later, in a manuscript from Bologna which translates as Secrets for Colour. It gives a curious recipe for a water to soften bones: ‘Take common salt and Roman vitriol in equal quantities, and grind them very well together; then distil them through an alembic, and keep the distilled water in a vessel well closed.’ As we saw in Chapter 3, ‘Roman vitriol’ is a hydrated metal sulfate, probably iron or copper sulfate; its mixture with salt, when heated, produces water and hydrogen chloride, which together form the acid solution. Later texts from the sixteenth and seventeenth centuries include similar methods to prepare this so-called spirit of salt, or ‘oyle of salt’. The first mentioned use, to soften bones, is indeed best achieved with hydrochloric acid, which readily dissolves the minerals from bone to leave only the organic matter largely intact. Leave a chicken bone in dilute hydrochloric acid for a few hours, and it may easily be bent without breaking.
What’s Just?
Authors: Dryzek John S. , Norgaard Richard B. , Schlosberg David
Published: November 2020

Climate change is a collective global issue that requires a collective response—but that is not its whole story. Those most responsible for the existence of problems (industrialized societies with a long history of emissions) are not the same people or countries as those likely to be most affected by the consequences. Nor are they necessarily the same as those most capable of doing something; so for example China has a capacity that is much greater than its historical responsibility. What this means is that major questions of justice arise in the distribution of the burdens and benefits of action (and inaction). Climate change crystallizes questions that pervade many global issues, and so provides a crucial arena for thinking about how to pursue justice in general. How then do we use justice to frame social responses to a climate-changing world? Any response here is complicated by the fact that justice itself is what political theorists call an “essentially contested concept” on which agreement is not possible, even in theory, despite the philosophical industry that addresses the concept. Further, and strikingly in the case of climate change, the range of injustices experienced can become “compound” when existing ones make new ones even worse (Shue, 1992). For two decades climate justice has been addressed and contested by negotiators, social movements, and philosophers. Justice means different things to different people at different stages of climate change. We examine definitions of justice in ethical theory, in its articulation in global negotiations, and for movements that demand it. While there is some general agreement on injustices in the causes and effects of climate change, justice claims can differ strikingly, and sometimes clash. We also explore the prospects for justice in adaptation to climate change. Key dimensions of climate justice were identified in the original agreement of UNFCCC in 1992. This specified that nations would work to “protect the climate system for the benefit of present and future generations of mankind, on the basis of equity and in accordance with their common but differentiated responsibilities and respective capacities.”
Modern working life and organizations— change, dynamism, and post-bureaucracy?
Authors: Alvesson Mats
Published: November 2020

Today’s working life can be understood in terms of grandiose ideas, illusion tricks, and zero-sum games. These three concepts provide a rather different perspective than conventional understandings of working life phenomena suggested by signifiers such as leadership, visions, strategy, change, entrepreneurship, innovations, and human resource management. Chapters 6–9 deal with four key themes in current organizations and working conditions. The first theme, addressed in this chapter, is ideas about major, drastic changes. People refer to the demise of bureaucracy and mass production, a transition to new forms of production and work organizations characterized by flexibility, dynamism, networks, knowledge intensive work, flat organizations, and so on. This is worth investigating, which is what this chapter aims to do. The second theme, which is tackled in Chapter 7, is concerned with the way in which organizations try to create legitimacy in relation to the predominant norms and ideas through formal structures signalling ‘the right practice’, without necessarily affecting the latter to any appreciable degree—in other words, an illusion trick. The idea is that organizations are increasingly devoting their time and energy to developing shop-window arrangements—designed to satisfy various groups interested in what is going on in a given organization, but without deeper insights into its workings. The third theme, covered in Chapter 8, discusses how various occupational groups are trying to advance their positions and gain status as professionals (experts) in line with ideas about the increased importance of knowledge and expertise. They try to get a hearing for their claims for a unique and superior ‘competence’ that entitles them a higher status and monopoly of a given sector of the labour market. People who are not formally qualified are kept at bay. Advancing positions through professionalization is not always so simple, however, since other groups have the same ambition. This involves, for example, personnel specialists, marketers, and nurses. The fourth theme is leadership, or rather ‘leadership’, which is discussed in Chapter 9.
Leadership—a driving force or empty talk?
Authors: Alvesson Mats
Published: November 2020

However, if, as we have seen, more education, training, and professionalization is not always the ideal way to improve society and its institutions, maybe leadership can do the trick and achieve fine results? And maybe this is the answer to the frustrations experienced by many groups and individuals? Perhaps good leadership can lead to a better working life and results that will satisfy shareholders and tax payers? This is what is claimed, on a broad front today—perhaps somewhat too widely. Leadership can be seen as a way of boosting the status and position of managers. Going from mere managers to becoming leaders parallels the efforts many occupations undergo to become more professional. ‘Leadershipization’ and professionalization can therefore be seen as parallel phenomena, triggering and reinforcing each other. The status boosting of groups of employees makes managers extra eager to add a new impressive quality to what they do. Recent decades have witnessed an enormous expansion of interest in ‘leadership’. Contemporary discussion and books about managerial leadership certainly cover a broad terrain, and there are no limits to what leadership is supposed to accomplish in terms of improving the feelings, thinking, values, ethics, change-mindedness, and the satisfaction and performance of followers (subordinates). The leader has become one of the dominant heroes of our time—even a mythical figure. When faced with major crises or even mediocre performances, cries for superior leadership are heard. All kinds of institutions, from firms to schools and universities to churches, are supposed to benefit greatly from more and better leadership. Whatever the problem, leadership has become the solution, and it is a standard recipe for success. Much of this interest in leadership revolves around change and development, and the ability of leaders to get people involved in and committed to opportunities beyond their everyday realities. Employees may be bored, tired, or alienated at work, but effective leadership is expected to address such problems. Followers are thought to be inspired and influenced by leaders, thus overcoming uncertainty, narrow mindedness, and low motivation.
The costs of grandiosity
Authors: Alvesson Mats
Published: November 2020

A critical reader might well ask at this point: What is the real problem? Why is this author so worried about what most people may see as positive things in life: increased consumption, more education, promises about a working life with stronger ingredients of milk and honey? The sceptical reader may want to challenge this text and pose the following critical questions: . Why not just accept what people want? Isn’t it natural that people want more—and more? Of course, people are looking for more things and want to increase their consumption. And if they want to pay the earth for things with certain brand names, maybe they will be more satisfied with that? . So what if there is a lot of higher education, even if all the graduates do not get jobs? It’s good to keep people occupied and out of the way in a cheap and agreeable manner. And don’t the students always learn something in all these courses? They don’t perhaps become smarter, but education is better than unemployment. . Why not permit new and finer titles and labels? Why not make elites and others happy through using knowledge vocabulary to describe society, economy, and the population? And if all these university colleges, polytechnics, and other higher education institutions want to call themselves universities, why not be generous? The division between universities and university colleges only favours those snobs who work or study at the former places. And the liberal awarding of titles like ‘marketing director’ and ‘professor’ might give the people concerned a nice title on their business cards and make them happier, perhaps more motivated, and make their spouses proud. . Who cares about ‘real’ equality of opportunity for women and minorities if there are fine equal opportunity policies and programmes? If we have a sufficient number of women who are promoted to fill their quotas on the board and in higher education, we will have sufficient equality to comply with the statistics, and then everyone can be happy.
Death at Number
Authors: Öhrström Lars
Published: November 2020

The five others went first, one by one, and contemporary sources noted how humane the spectacle was, as the participants did not need to see each other. Thousands of Stockholmers had turned out to watch, on this cold day of 30 January 1744, as the last of the six, Gustaf Schedin, accountant at the Insjö copper works, mounted the scaffold. As the culmination of the show, he would be both beheaded and then cut to pieces. The summer before, Schedin had led the fourth Dalecarlian Rebellion: the last march of the free miners and farmers of Dalarna— the mine-rich county 100 miles north-west of Stockholm—to the Swedish capital, in a movement expressing raging discontent with the king, Fredrik I, and his disastrous war with Russia. This sort of thing had been successful before: the fiercely independent-minded people of Dalarna traditionally wielded a certain power, rich as they were in natural resources—the jewel in the crown being the famous Great Copper Mountain mine in Falun. Once it was the largest of its kind in the world, and yielded something like 70 per cent of the world’s copper production. The Falun mine, like many others, was once managed as a cooperative operation, and worked by free miners called mountain-men (bergsmän) with special privileges and laws of their own. But their time was at an end. In 1743 the uprising ended in a bloodbath in Stockholm, and now the six leaders were to be executed. The copper mine was also losing its privileged position. It had given the Swedish kings and queens economic strength for numerous more-or-less successful military adventures down in continental Europe, but was now in decline, and so was the military power of Sweden. This traditionally male activity—becoming angry and getting the lads together to sort things and people out—is chemically related to high levels of the large organic molecule testosterone. For a inorganic chemist inclined to find a good story, it would have been great to now present a direct link between copper and the way we make this molecule in our bodies, starting from cholesterol, claiming that this made the men from Dalarna more inclined to hasty revolutionary actions.
The Last Alchemist in Paris
Authors: Öhrström Lars
Published: November 2020

The Periodic Table is packed with elements. This is hardly surprising, but it is also full of numbers: atomic numbers obviously, the number of protons in the nuclei, that form the address of an element in the table, but also atomic weights, number of isotopes, and any other property directly linked to the atom in question. In short, if you are inclined towards numerology and proving your favourite theory by combining two or more numbers to give a pleasing figure or neat coincidence, you have more opportunities here than with all the pyramids of Egypt combined. For example, gold (Au) has 79 protons and so consequently atomic number 79. Yttrium (Y), the first of seven elements to be found and named after the mine in Ytterby on Resaro Island in the Stockholm archipelago, has atomic number 39. One of the later discoveries from the same mine was scandium, atomic number 21, in 1879. Add these two numbers and you get 60, a common enough street number, but of special significance in this chapter. Divide 39 by 13, the number of bad luck, and you get 3, the atomic number of lithium (Li). In February 1896, a curious man in something of a state, and not touched by good luck for some time, checked in to the Hotel Orfila, on rue d’Assas 60, close to the Jardin du Luxembourg in Paris. As the foremost chronicler of the Stockholm archipelago, he would have been familiar with the mine on Resaro, and as a failed chemistry student he would have known about yttrium. He bluntly refused room number 13, installed himself in another chamber and set out to make gold. He was the celebrated novelist and playwright August Strindberg, aged 47, the atomic number of silver. He was also an accomplished painter, and thus a man of many talents, self-esteem being not the least of these. He set up his laboratory here, not far from Marie and Pierre Curie’s Sorbonne buildings, for he was going to show them all—the dusty old professors at Uppsala University, and especially that fraud Mendeleev with his proposed Periodic Table.
Two Brilliant Careers
Authors: Öhrström Lars
Published: November 2020

At the time of publishing, it is exactly 50 years since Bob Dylan answered a number of enigmatic questions with the ambiguous line ‘the answer is blowin’ in the wind’ on the A-side of the record The Freewheelin’ Bob Dylan. But one of these, ‘How many years can a mountain exist before it’s washed to the sea?’ we can at least try to answer, as part of the solution lies in one of the more famous rules of thumb one learns as a novice chemist: positively charged metal ions combined with oxides (O2−), sulphides (S2−), phosphates (PO43− ), silicates (SiO42−), and carbonates (CO32−), are insoluble in water, whereas similar nitrates (NO3− ), chlorides (Cl−), and bromides (Br−), are soluble. In terms of stuff you’ve got in your kitchen, this means that when you put a spoon of table salt (NaCl) into water it will ‘disappear’, faster if you stir or heat, and the water will look exactly the same as before. For the insoluble stuff, we move to the more expensive regions of the cupboards and investigate the state of our silver and copperware. When things like these were to be on display, my mother used to have me clean them with silver or copper polish, as the oxides and sulphides tarnishing the metal surfaces did not go away in a normal wash with water—they are completely insoluble. A suitable but boring exercise, and as close to a chemistry set as I ever came as a child. What they normally don’t tell you in chemistry textbooks however, are the enormous consequences of these rules, visible all over the world. Why are mountains made of rocks from oxides, sulphides, phosphates, silicates, and carbonates? Because they are insoluble! Any mountains made from sodium chloride would indeed have been ‘washed to the sea’ thousands of years ago, and where NaCl can be mined it is also known as rock salt, and found either underground or in regions with a very dry climate. Which brings us to the hero and heroine if this chapter.
Special Activities
Authors: Colbert Dom
Published: November 2020

Drowning is a hazard for the international traveller whether swimming, snorkeling, scuba diving, or boating. Alcohol always exacerbates the danger. Drowning in children is a particular problem. In one British study (1996–2003) 74% of drowning in children <14 years old occurred in swimming pools.
Medical Care Overseas
Authors: Colbert Dom
Published: November 2020

One is never really prepared for a mishap or an illness overseas, and whenever such an eventuality occurs one is faced with the problem of accessing the best local treatment. The travel health provider at home should always advise the traveller about the need to check out travel insurance and local medical facilities in the destination before travel, especially in the case of long-term or high-risk travellers. In addition, the traveller should be given a contact number for the clinic in his or her home country and be instructed to use this contact whenever necessary.
The Returned Traveller
Authors: Colbert Dom
Published: November 2020

Respiratory illness, fever, diarrhoea, and dermatitis are the four most frequent medical problems in the returned traveller. Unexplained fever is the most urgent of these because febrile conditions such as malaria, meningitis, and typhoid can all deteriorate rapidly and become life-threatening. Respiratory infections are also very common and are often viral in origin. A persistent cough or a doubtful CXR warrants further investigation. Diarrhoea that persists may well be helminthic in origin with giardiasis high on the list. In cases already treated with antibiotics one must consider C. difficile infection while the unmasking of inflammatory bowel disease or irritable bowel syndrome is probably more common than supposed. Dermatitis is often due to exacerbation of an existing condition, e.g. psoriasis or eczema. Tropical-related dermatitis is most frequently due to infected arthropod bites. CLM is the main parasitic cause. Exanthems and enanthems occur in a variety of systemic conditions ranging from acute HIV to dengue fever to coxsackie infection. Rashes are seldom diagnostic unless the cause is obvious, e.g. scabies or typhoid (rose spots). In all cases the practitioner should adhere to a strict protocol that involves a good history, careful physical examination, and routine screening and microscopy of blood, urine, and stool. Simple X-rays and ultrasound examination may also be considered. In no case should the practitioner hesitate to refer the patient to a specialist physician. Nowadays computer-assisted diagnosis is becoming more popular and more reliable. The Kabisa Travel System, developed in Antwerp, has been shown to perform equally well with travel physicians in diagnosing the cause of fever in those returned from a tropical environment. Kabisa is the Swaili word for ‘hand in the fire, I am absolutely certain’!