bluuebunny/crossref_metadata_2025 huggingface dataset:
Quaternary Climatic Changes and Landscape Evolution
Authors: Ehlers Jürgen
Published: November 2020

The last 2–3 Ma have witnessed climatic changes of a scale unknown to the preceding 300 Ma. In the cold periods vegetation was reduced to a steppe, giving rise to large-scale aeolian deposition of sand and loess and river sands and gravels. In the warm stages, flora and fauna recolonized the region. Parts of Europe were repeatedly covered by mountain glaciers or continental ice sheets which brought along huge amounts of unweathered rock debris from their source areas. The ice sheets dammed rivers and redirected drainage towards the North Sea. They created a new, glacial landscape. This chapter presents an outline of the climatic history, and in particular the glacial processes involved in shaping the landscapes of western Europe. By convention, geologists generally tend to draw stratigraphical boundaries in marine deposits because they are more likely to represent continuous sedimentation and relatively consistent environments in comparison to terrestrial sediments. However, marine deposits from the period in question are relatively rarely exposed at the surface. According to a conclusion of the International Geological Congress 1948 the Tertiary/Quaternary boundary was defined as the base of the marine deposits of the Calabrian in southern Italy. In the Calabrian sediments fossils are found that reflect a very distinct climatic cooling (amongst others the foraminifer Hyalinea baltica). This climatic change roughly coincides with a reversal of the earth’s magnetic field; it is situated at the upper boundary of what is called the Olduvai Event. Consequently, it is relatively easy to identify; its age is today estimated at 1.77 Ma (Shackleton et al. 1990). However, in contrast to the older parts of the earth’s history, the significant changes within the Quaternary are not changes in faunal composition but changes in climate. For reasons of long-term climatic evolution the base of the Calabrian is not a very suitable global boundary. Its adoption excludes some of the major glaciations from the Quaternary. Therefore, in major parts of Europe another Tertiary/Quaternary boundary is in use, based on the stratigraphy of the Lower Rhine area (e.g. Zagwijn 1989). Here the most significant climatic change is already recorded as far back as the Gauss/Matuyama magnetic reversal (some 2.6 Ma ago).
Periglacial Geomorphology
Authors: Kolstrup Else
Published: November 2020

Many present landscape elements in western and central Europe are to a large extent the result of periglacial processes that prevailed during cold periods more than 10,000 years ago. As with the glacial chapter, this account of the periglacial geomorphology also needs to base itself upon processes that no longer or only to a limited extent take place in the areas today. Consequently, this chapter will include an overview of some of the most important periglacial processes and deposits and their effects upon landscape development as influenced by variations in periglacial environmental conditions, lithology, and vegetation cover. Most landscapes that were glaciated during the Weichselian have accentuated relief, especially where subsequent human modification has been relatively modest. It is probable that the glaciated parts of Europe were also accentuated after the Saalian glaciation, but today smooth surfaces and gentle slopes characterize the Saalian areas. During interglacial periods relatively little landscape modification has taken place, and the difference in morphology between the Weichselian glacial landscape and the areas beyond is mainly due to the activity of periglacial processes. As a consequence these European landscapes can be regarded as periglacial. Even where a periglacial overprinting can be strongly demonstrated in the geomorphology of many western European landscapes the expression ‘periglacial landscape’ has not been widely used. There may be two main reasons for this. First, even if landforms resulting from periglacial processes may be geographically widespread, they are not normally as eye-catching and morphologically diverse on a local scale as are those resulting from glacial activity. Secondly, it is difficult to geographically delimit a periglacial area: in relation to a glaciated area where the criterion is whether the ice was there or not, the delineation of a periglacial area is dependent on much more subtle features and arbitrary criteria. Further, landscapes that show general imprints of past periglacial conditions often contain areas that bear identifiable imprints of the dominant activity of a single agent, such as water, wind, or gravity. Even if some of these activities may be particularly efficient in cold climates, they are nevertheless of a wider occurrence.
Identifying Foragers and Farmers
Authors: Barker Graeme
Published: November 2020

One of the most exciting aspects of studying transitions from foraging to farming is the extraordinary range of evidence available, and the necessary interdisciplinarity of the exercise (Barker and Grant, 1999; Dincauze, 2000). The primary data for whether prehistoric people were living as foragers or farmers (or combining activities, as was often the case) have been collected by archaeologists, from their surveys and excavations. For much of the history of study, subsistence patterns were inferred principally from interpretations of artefacts, settlements, and associated structures. More recently, studies of artefact use have been strengthened by the application of techniques of physical and chemical analyses of food residues attached to them. A vital strand of research has been on the environmental contexts in which early farming took place. Such studies, of sediments, soils, and the microscopic flora and fauna they contain, have contributed reconstructions at a wide variety of scales, from regional climatic and environmental histories of late Pleistocene and Holocene climatic change to the landscapes of single occupation sites—the recognition of signs of animal stalling, for example. From the 1960s onwards, priority has also been given on archaeological excavations to the collection of the organic materials that survive in many conditions such as fragments of animal bone and seeds and other fragments of plants, waste discarded from the consumption of food that is the primary evidence for systems of subsistence. In certain conditions even faeces may survive, telling us about individual meals. Human teeth and bone provide further information about diet. Molecular biology is a new and exciting area of current research, with modern and ancient DNA (aDNA) being used to infer population histories and domestication processes (Jobling et al., 2004; M. Jones, 2001; Renfrew and Boyle, 2000). Further contributions have come from linguistics: studies of present-day languages have been used in support of theories about how farming was spread by new language groups (Bellwood and Renfrew, 2002). The art systems created by foragers and early farmers are yet another source of information, amongst the most intriguing for their potential insights about the beliefs of the people who created them. In short, there is a remarkably broad church of disciplines with contributions to offer, though integrating their findings can be challenging.
The ‘Hearth of Domestication’? Transitions to Farming in South-West Asia
Authors: Barker Graeme
Published: November 2020

The principal focus of this chapter is the classic zone of early farming research from the 1960s onwards, the so-called ‘hilly flanks of the Fertile Crescent’ in South-West Asia (Fig. 4.1). This region is normally defined as the arc of hill country to the west of the Syrian desert and to the north and east of the Tigris and Euphrates valleys. The western side of the arc begins east of the Nile in the Sinai and the Gulf of Arabah on the southern border of Israel and Jordan; it continues northwards as the hill country on either side of the Jordan rift valley in Israel, Palestine, Lebanon, western Jordan, and western Syria (the so-called ‘Levantine corridor’); and extends westwards to the Mediterranean littoral. The northern sector is formed by the Taurus mountains along the southern edge of the Anatolian plateau, which curve eastwards from the Mediterranean coast in northern Syria to form the present-day Syrian–Turkish border. The eastern sector consists of the Zagros mountains, running south-eastwards from eastern Turkey and north-west Iran to the Persian Gulf, forming the Iraq–Iran border for most of their length, and continuing in south-west Iran beyond the Persian Gulf towards the Straits of Hormuz. The region also embraces adjacent zones: the alluvial plains of the Tigris and Euphrates rivers and the vast tracts of steppe and desert country separating them from the Levantine, Taurus, and Zagros upland systems; the Anatolian plateau to the north of the Taurus, within modern Turkey; and the Iranian plateau east of the Zagros, within modern Iran. The archaeological literature commonly uses the term Near East to describe the main region of interest, with the Levant for its western side (a term also used in this chapter), and South-West Asia for the eastern side, but the entire region is more correctly termed South-West Asia. The upland areas of the region mostly receive more than 200 millimetres of rainfall a year, which is the minimum required for growing cereals without irrigation. Rainfall decreases drastically moving out into the steppe and desert zones.
The Horse in the Palaeolithic Parietal Art of the Quercy: Outline of a Stylistic Study
Authors: Lorblanchet Michel
Published: November 2020

The discovery of the engravings at Church Hole brings numerous and precious newelements that renew our knowledge of Palaeolithic parietal art. In particular, it poses the problem of styles in the closing phase of the Palaeolithic. As a comparison, I will present here an outline of the evolution of styles in the Palaeolithic parietal art of the Quercy between about 27,000–28,000 and 12,000–13,000 years ago. In order to clearly highlight the value of such an evolution, I shall begin by comparing various horse figures, since these are the dominant subjects in all phases of this long period. I shall start by comparing the equids of the cave of Roucadour with those (likewise unpublished) of the cave of Combe Nègre 1 (Lot), and then those of the caves of Sainte-Eulalie and Pergouset (Lot), and I shall end by recalling the characteristics of the horses of Pestillac and Lagrave which illustrate the end of the parietal Magdalenian in our region. I will make one last comparison with the portable art of the abri Murat (Lot) which yielded horse depictions in an azilian level. The cave of Roucadour, vast and of easy access, is in the northern part of the Causse de Gramat (Lot). Its total length is about 300 m, and it constituted a very attractive site for man during a large part of prehistory. During the neolithic and protohistory, a habitation (excavated by A. Niederlender and then by J. Gasco) was installed in front of the cave entrance. The deep galleries were also used in the same period, since quantities of pottery, burials, and bronze objects were discovered there. In 1962, two speleologists, Pierre Taurisson and Jean Paul Coussy, discovered parietal paintings and engravings in a lateral gallery. The cave was classed as a historical monument in 1964. The study and recording of the engravings were entrusted to the abbé André Glory, assisted by his collaborator, the abbé Jean-Louis Villeveygoux; the discoverers themselves also seem to have lent their help at the start. André Glory, who was then an engineer in the CNRS, had just finished tracing the decoration of Lascaux. He carried out four campaigns of recording at Roucadour from 1964 to 1965 (Glory 1964, 1966). A tragic road accident in 1966 cost him and his assistant their lives.
Rock Art and the Côa Valley Archaeological Park: A Case Study in the Preservation of Portugal’s Prehistoric Rupestral Heritage
Authors: Baptista António Martinho , Fernandes António Pedro Batarda
Published: November 2020

Although Nelson Rebanda—the archaeologist working for the electricity company (EDP) that was building a dam in the Côa river—probably discovered the first Côa Valley engraved surface with Palaeolithic motifs (the now well-known Rock 1 of Canada do Inferno) in November 1991, the find was only revealed to the public in November 1994 (Jorge 1995; Rebanda 1995). Subsequently, the first reports on ‘important archaeological finds in the Côa Valley’ started to appear in the newspapers. The Canada do Inferno engravings were located upstream and very near to the construction site of the Côa dam. The construction work advanced at a good pace and the completion of the dam would irremediably destroy the engravings. The public revelation of the find instantly triggered a huge controversy since the first specialists to visit the site immediately classified the engravings as being of Palaeolithic style. As a result of the media attention on the Côa and right after the broadcast of the first TV reports, a pilgrimage to the Côa Valley rock-art surfaces began. Reacting to the first news on an affair that was starting to be known as ‘the Côa scandal’, IPPAR (the state body that, at the time, was in charge of managing archaeology in Portugal) created, at the end of November 1994, a committee to follow the archaeological rescue work being done in the Côa. Nevertheless, and considering the serious problem created by the construction of the dam (and the construction work continued), it rapidly became evident that IPPAR was gradually losing control over the situation as it shifted to the public domain. In December 1994, IPPAR asked UNESCO for an expert opinion to challenge the efforts of EDP (the Portuguese Power Company responsible for the construction of the dam and at the time totally state owned) to demonstrate that the Côa findings were not of Palaeolithic chronology. Throughout 1995, this would be a crucial issue since some defended the position that, if the engravings were not Palaeolithic, their patrimonial value would not be very important and, therefore, the dam could be built!
Intermezzo
Authors: Dasgupta Subrata
Published: November 2020

By the end of World War II, independent of one another (and sometimes in mutual ignorance), a small assortment of highly creative minds—mathematicians, engineers, physicists, astronomers, and even an actuary, some working in solitary mode, some in twos or threes, others in small teams, some backed by corporations, others by governments, many driven by the imperative of war—had developed a shadowy shape of what the elusive Holy Grail of automatic computing might look like. They may not have been able to define a priori the nature of this entity, but they were beginning to grasp how they might recognize it when they saw it. Which brings us to the nature of a computational paradigm. Ever since the historian and philosopher of science Thomas Kuhn (1922–1996) published The Structure of Scientific Revolutions (1962), we have all become ultraconscious of the concept and significance of the paradigm, not just in the scientific context (with which Kuhn was concerned), but in all intellectual and cultural discourse. A paradigm is a complex network of theories, models, procedures and practices, exemplars, and philosophical assumptions and values that establishes a framework within which scientists in a given field identify and solve problems. A paradigm, in effect, defines a community of scientists; it determines their shared working culture as scientists in a branch of science and a shared mentality. A hallmark of a mature science, according to Kuhn, is the emergence of a dominant paradigm to which a majority of scientists in that field of science adhere and broadly, although not necessarily in detail, agree on. In particular, they agree on the fundamental philosophical assumptions and values that oversee the science in question; its methods of experimental and analytical inquiry; and its major theories, laws, and principles. A scientist “grows up” inside a paradigm, beginning from his earliest formal training in a science in high school, through undergraduate and graduate schools, through doctoral work into postdoctoral days. Scientists nurtured within and by a paradigm more or less speak the same language, understand the same terms, and read the same texts (which codify the paradigm).
A Liminal Artifact of an Uncommon Nature
Authors: Dasgupta Subrata
Published: November 2020

The story so far has been a narrative about the development of two very contrasting types of computational artifacts. On the one hand, Alan Turing conceived the idea of a purely abstract and formal artifact—the Turing machine—having no physical reality whatsoever, an artifact that belongs to the same realm of symbols and symbol manipulation, as do mathematical objects. On the other hand, the major part of this narrative has been concerned with a material artifact, the computer as a physical machine that, ultimately, must obey the laws of physics—in particular, the laws governing electromagnetism and mechanics. This was as true for Babbage’s machines (which were purely mechanical) as for Hollerith’s tabulator, as true for the electromechanical machines, as for the Harvard Mark I and the Bell Telephone computers, as true for the ABC and the ENIAC, as for the EDSAC and the Manchester Mark I. Beginning with the EDVAC report, and especially manifest in the development of the first operational stored-program computers, was the dawning awareness of a totally new kind of artifact, the likes of which had never been encountered before. Philosophers speak of the ontology of something to mean the essential nature of that thing, what it means to be that thing. The ontology of this new kind of artifact belonged neither to the familiar realm of the physical world nor the equally familiar realm of the abstract world. Rather, it had characteristics that looked toward both the physical and the abstract. Like Janus, the Roman god of gates, it looked in two opposite directions: a two-faced artifact—which, as we will see, served as the interface between the physical and the abstract, between the human and the automaton; a liminal artifact, hovering ontologically between and betwixt the material and the abstract (see Prologue, Section IV ). So uncommon was this breed that even a name for it was slow to be coined. During the Cambridge conference in England in 1949, we find a session devoted to programming and coding.
Statins: Protection Against Heart Attacks and Strokes—Hallelujah!
Authors: Cordes Eugene H.
Published: November 2020

Cholesterol! This may be the single most famous (or infamous) small molecule of life. Most people view it as a threat to good health and even to life itself. We search for foods that are cholesterol free or at least low in cholesterol. We use them in efforts to achieve a low-cholesterol diet. Our primary care physicians measure our blood cholesterol levels routinely and report the news, good and bad. If the level is high, they recommend a better diet (that is, one lower in cholesterol and saturated fat), more exercise, and perhaps weight reduction. If those measures fail to get the cholesterol level where it should be, it is highly likely that therapy with a cholesterol-lowering drug will be recommended. The drug will usually fall into a class known as statins. Statins are among the most frequently prescribed drugs in the world. The first statin approved for marketing by the FDA in the United States was lovastatin (Mevacor), which happened in 1987. Lovastatin was followed into clinical practice by pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), cerivastatin (Baychol), pitivastatin (Livalo), and rosuvastatin (Crestor). There are a lot of options from which to choose among the statins. The story of how statins were discovered and developed is pretty amazing. The tale focuses on cholesterol in its several dimensions—what it is, how it is made, how its levels are regulated, the health consequences that may ensue when proper regulation fails, and how statins act to restore that regulation. The task of this chapter is to tell the tale. The focal point is cholesterol. So that is where we begin. There are two sides to most stories, which is certainly the case for cholesterol. Although what we hear about cholesterol is mostly negative (isn’t there some way to get rid of this stuff?), the fact is, we cannot live without it and there are three reasons why. First, cholesterol is an essential component of all our membranes.
Fludalanine: Nice Try But No Hallelujah
Authors: Cordes Eugene H.
Published: November 2020

It is time that we experienced a tale of failure. As I have stated repeatedly, most drug discovery efforts fail. Choice of the wrong target dooms the effort from the start. Screening may fail to turn up actives, and molecular design may do no better. Given active molecules, medicinal chemistry efforts to improve properties may fail. Senior management’s heavy hand may terminate a promising effort. If one gets as far as development, a safety or efficacy issue may derail the project. Then, too, competitors may outrun you or financial support may dry up. There are many ways to fail, not so many to succeed. All five stories told so far have been successes: finasteride, ACE inhibitors, statins, imipenem/cilastatin, and the avermectins. Chapter 12 provides another example of a success: the gliptins. In this chapter, however, I pull together the threads of a failure: fludalanine. It is the most interesting failed drug discovery story that I know. There is much to learn from it, particularly about problem solving. It has a couple of surprises. By way of background, Merck had set its mind on finding an effective orally active antibiotic, driven in substantial part by the insistence of Max Tishler, Merck’s determined head of research. Orally active antibiotics are attractive. A patient with a bacterial infection may be treated in the hospital with an oral or a parenteral agent, one given by injection or inhalation. An injectable antibiotic may be given intravenously, intramuscularly, or subcutaneously. However, when the patient has been released from the hospital and sent home, it is convenient to have an antibiotic that can be taken by mouth, a tablet or capsule, for continued action against the infection. Ideally, an antibiotic should be available in both a parenteral (intravenous, intramuscular, or subcutaneous) formulation and an orally active formulation. In this way, the patient can be maintained on the same antibiotic when returning home from the hospital. Merck was having trouble meeting its objective.
Site Selection and Soil Preparation
Authors: White Robert E.
Published: November 2020

As outlined in chapter 1, “determining the site” in old established wine regions such as Burgundy, Tuscany, and the Rheingau has been achieved through centuries of acquired knowledge of the interaction between climate, soil, and grape variety. Commonly, vines were planted on the shallow soils of steep slopes, leaving the more productive lower terraces and flood plains for the cultivation of cereal crops and other food staples, as shown, for example, by the vineyards along the Rhine River in Germany. The small vineyard blocks of the Rhine River, the Côte d’Or, Valais and Vaud regions of Switzerland allowed winegrowers to dif­ferentiate sites on the basis of the most favorable combination of local climate and soil, which underpinned the concept of terroir. In much of the New World, by contrast, where agricultural land was abundant and population pressure less, vineyards have been established on the better soils of the plains and river valleys, as exemplified by such regions as the Central Valley of California, the Riverina in New South Wales, Australia, and Marlborough in New Zealand. Apart from the availability of land, the overriding factor governing site selection was climate and the suitability of particular varieties to the prevailing regional climate. In such regions, although soil variability undoubtedly occurred, plantings of a single variety were made on large areas and vineyard blocks managed as one unit. Soil type and soil variability were largely ignored. Notwithstanding this approach to viticulture in New World countries, in recent time winegrowers aiming at the premium end of the market have become more focused on matching grape varieties to soil and climate and adopting winemaking techniques to attain specific outcomes for their products. For established vineyards, one obvious result of this change is the appearance of “single vineyard” wines that are promoted as expressing the sense of place or terroir. Another reflection of this attitudinal change is the application of precision viticulture (see “Managing Natural Soil Variability in a Vineyard,” chapter 6), whereby vineyard management and harvesting are tailored to the variable expression of soil and local climate in the yield and sensory characteristics of the fruit and wine.
The Good, Bad, and Ugly of Coal and Gas
Authors: Fox Michael H.
Published: November 2020

About ten miles north of where I live in northern Colorado, a smokestack rises 500 feet in the air alongside a stair-step series of buildings. On a summer day, nothing appears to be coming from the smokestack, as though it is a ghostly relic; in the winter, a white plume rises. On closer approach, a lake teeming with ducks, geese, pelicans, and other waterfowl sits in the foreground. A herd of American bison roam on over 4,000 acres of grasslands surrounding the smokestack. This apparently benign plant called Rawhide Energy Station is actually a 280 MWe coal-fired power plant that provides about one-quarter of the electricity for four nearby communities—Fort Collins, Loveland, Longmont, and Estes Park. It is a public utility owned by the four communities and is near state-of-the-art for a coal-fired power plant, being one of the most efficient in the western United States and among the top ten in lowest emissions. I drove up to the Rawhide Energy Station and called on an intercom box to the security station to identify myself so the guard could open the security gate for me to enter. After driving across the edge of the lake, the armed guard then directed me to the visitor center. I met Jon Little, the knowledgeable and friendly tour guide, and a group of bicyclists from a local environmentally conscious brewery who were taking the tour also. We put on headphones with a radio set and a hard hat for the tour. The first and largest building houses the boiler and the generators. Th e coal arrives by train in five- to six-inch lumps, which are broken down into one-inch lumps before being fed by conveyor to grinders that convert it into a powder finer than facial powder. This powder is then mixed with air and blown into the 16-story. boiler from four directions, where it burns efficiently at a hellish temperature of 2,800˚F.
Low Carbon Energy Transitions
Authors: Araújo Kathleen
Published: November 2020

The world is at a pivotal crossroad in energy choices. There is a strong sense that our use of energy must be more sustainable. Moreover, many also broadly agree that a way must be found to rely increasingly on lower carbon energy sources. However, no single or clear solution exists on the means to carry out such a shift at either a national or international level. Traditional energy planning (when done) has revolved around limited cost projections that often fail to take longer term evidence and interactions of a wider set of factors into account. The good news is that evidence does exist on such change in case studies of different nations shifting toward low-carbon energy approaches. In fact, such shifts can occur quite quickly at times, alongside industrial and societal advance, innovation, and policy learning. These types of insights will be important for informing energy debates and decision-making going forward. Low Carbon Energy Transitions: Turning Points in National Policy and Innovation takes an in-depth look at four energy transitions that have occurred since the global oil crisis of 1973: Brazilian biofuels, Danish wind power, French nuclear power, and Icelandic geothermal energy. With these cases, Dr. Araújo argues that significant nationwide shifts to low-carbon energy can occur in under fifteen years, and that technological complexity is not necessarily a major impediment to such shifts. Dr. Araújo draws on more than five years of research, and interviews with over 120 different scientists, government workers, academics, and members of civil society in completing this study. Low Carbon Energy Transitions is written for for professionals in energy, the environment and policy as well as for students and citizens who are interested in critical decisions about energy sustainability. Technology briefings are provided for each of the major technologies in this book, so that scientific and non-scientific readers can engage in more even discussions about the choices that are involved.
Amlodipine (Novasc)
Authors: Li Jie Jack
Published: November 2020

Hypertension (high blood pressure) is estimated to afflict 1 billion individuals worldwide and is a major risk factor for stroke, coronary artery disease, heart failure, and end-stage renal disease. The first class of drugs to treat hypertension was the mercurial diuretics, discovered by Alfred Vogl in 1919 in Vienna. Diuretics, by removing fluid from the body, reduce the pressure on the heart. Mercurial diuretics revolutionized the treatment of congestive heart failure resulting from severe edema and were the primary treatment until the late 1950s, when thiazide diuretics emerged. In 1957, Merck chemist Frederick C. Novello prepared chlorothiazide (2, Diuril), a potent diuretic that does not cause elevation of bicarbonate excretion, an undesired side effect associated with mercurial diuretics. Shortly after chlorothiazide’s (2) success, George deStevens at Ciba reduced a double bond on chlorothiazide (2) to a single bond to give hydrochlorothiazide (3, HydroDiuril) which was 10-fold more potent than the prototype 2. Hydrochlorothiazide was introduced to medical practice in 1959 and within a short time became the drug of choice for the treatment of mild hypertension. One of the liabilities of these drugs is thiazide diuretic-induced hyperglycemia. As early as 1948, Raymond P. Ahlquist at the Medical College of Georgia speculated that there were two types of adrenergic receptors (adrenoceptors in short), which he termed α-adrenoceptor and β-adrenoceptor, that are 7-transmembraned protein as GPCR. In 1957, Irwin H. Slater and C. E. Powell at Eli Lilly prepared dichloroisoprenaline (DCI, 4), the dichloro analog of isoprenaline; it was later found to be the first selective β-adrenoreceptor blocking reagent, also known as a β-blocker. However, DCI was not further pursued as a drug candidate because it had a marked undesirable stimulant effect on the heart, an intrinsic sympathomimetic action (ISA). Beginning in 1958, James Black at Imperial Chemical Industries (ICI) led a team to look for β-blockers that were devoid of the stimulant effect on the heart. In 1962, the first selective β-adrenoreceptor inhibitor pronethalol (5) was discovered but was withdrawn from further development when it was found to cause thymic tumors in mice.
Esomeprazole (Nexium)
Authors: Li Jie Jack
Published: November 2020

Gastric acid, hydrochloric acid (HCl), is essential to our digestion. It helps break down proteins, fats, and starches in our food into nutrients such as amino acids and carbohydrates that our body can absorb. Alas, there can be too much of a good thing. Too much secretion of gastric acid for too long can cause heartburn or acid reflux, also known as gastroesophageal reflux disease (GERD). In addition, having too much gastric acid for too long will damage the mucosa of the stomach and may cause ulcer and even stomach cancers! While the exact pathogenesis of ulcers is not known, theories abound. It is still a popular belief that ulcer is caused by stress. Thirty years ago, the discovery of Helicobacter pylori demonstrated that the bacterium contributes to gastritis and peptic ulcers. Regardless of the root of stomach ulcers, they are closely associated with excessive secretion of gastric acid, so that was what early ulcer drugs intended to treat. Dozens of antacids are on the market to neutralize excess HCl: For instance, Mylanta and Maalox contain Al(OH)3 and Mg(OH)2. Tums contains CaCO3. Alka-Seltzer contains NaHCO3 (baking soda). However, antacids only treat the symptoms of excessive acid secretion, and are therefore only effective as a short-term treatment. A better therapy would treat the causation of excessive acid secretion. Histamine-2 receptor antagonists work by blocking the receptors that are responsible for excessive acid secretion: the histamine- 2 receptors. As a consequence, they are more efficacious and have fewer adverse effects in comparison to conventional antacids. The fact that histamine stimulates gastric acid secretion in the stomach was first observed by Popielski in the 1920s. Popielski studied under Pavlov, who won the Nobel Prize (for Physiology or Medicine) in 1904 for his studies in digestive system, but who is now better known for his classical dog-conditioning experiments. As an independent researcher at the University of Kraków, Popielski discovered that histamine was a stimulant of gastric glands, and acted directly without the involvement of vagal nerves. After injecting histamine subcutaneously into gastric fistulas in dogs, Popielski observed copious gastric acid secretion and extremely high acidity in the dogs’ stomachs.
Changing the Nature of Scientists: Participating in the Long-Term Ecological Research Program
Authors: Willig Michael R. , Walker Lawrence R.
Published: November 2020

From the outside looking in, scientists are often characterized as old men in white laboratory coats, working in splendid isolation, usually within the confines of rather sterile looking laboratories. Of course, this image was never quite accurate for ecologists, who abandoned white laboratory coats for more field-appropriate boots and khaki pants, but who nonetheless typically worked alone or with the benefit of a faithful field assistant (Figure 1.1a). The late 1900s was a time of rapid change in the way in which ecological research was conducted, in part because of opportunities for support from governmental agencies. Especially critical in effecting these changes was grant support that would allow scientists to comprehensively investigate the intricate and complex ecological interactions between organisms and their environment from a long-term and site-based perspective. Such efforts often involved large and diverse groups of scientists representing multiple disciplinary perspectives and investigative approaches (Figure 1.1b). The US Long-Term Ecological Research (LTER) program, with support from the National Science Foundation (NSF), was one of the first governmental programs to catalyze long-term, site-based, multidisciplinary, and collaborative research. The scientific research arising from such support has been broad and deep, resulting in thousands of publications. The research insights have been integrated into a number of synthetic books, each dedicated to long-term research at a particular site in the LTER program (Knapp et al. 1998; Bowman and Seastedt 2001; Greenland, Goodin, and Smith 2003; Schachak et al. 2005; Magnuson, Kratz, and Henson 2005; Foster and Aber 2006; Chapin et al. 2006; Havstad, Huenneke, and Schlesinger 2006; Redman and Foster 2008; Lauenroth and Burke 2008; Brokaw et al. 2012). In contrast, the effects of the LTER program’s many innovations on the participating scientists have not been explored in a comprehensive or systematic fashion. This book provides a window into how scientists have changed as a consequence of participation in the LTER program. The LTER network of sites, begun in 1980, effectively implemented the first effort by the NSF to systematically fund long-term, site-based environmental research.
Science, Citizenship, and Humanities in the Ancient Forest of H. J. Andrews
Authors: Swanson Frederick J.
Published: November 2020

The H. J. Andrews Experimental Forest Long-Term Ecological Research (LTER) program has nurtured a large, highly interdisciplinary community that has been a wonderful seedbed for emergence of ideas from our group, and for my own growth as a scientist, educator, collaborator, and communicator. Collaborations for me as an individual and within the Andrews forest group have grown over the decades: research–land management since the 1950s, ecology–earth sciences since the early 1970s, biophysical sciences–social sciences since the early 1990s, and humanities–arts–sciences over the past dozen years. As a US Forest Service scientist in seamless collaboration with academic and land manager colleagues, the stable yet dynamic community that the LTER program fosters has served as a great platform for connecting science lessons with society through many means, ranging from development of regional conservation strategies and landscape management plans to storytelling. This is a practice of citizenship by individual scientists and by a science-based team. The sustained learning that the LTER program has underwritten gives scientists a foundation for communicating findings from science and discussing their implications with the public, and the forest itself is a great stage for these conversations. I have had a career of immersion in the International Biological Program (IBP) and in the LTER program since its inception. After completing graduate studies in geology in 1972, I had the good fortune to join the early stages of IBP in the Coniferous Forest Biome Project at the H. J. Andrews Experimental Forest (AND) in the Cascade Range of Oregon. Our team of forest and stream ecologists, and a few earth scientists, had the decade of the 1970s to coalesce, mature, and craft stories of the ecosystems of the Pacific Northwest. The Andrews forest was a wonderful place to do that. It has a complex, ancient forest with nearly 100-m tall trees and fast, cold, clear, mountain streams whose beauty and chill takes your breath away. The year 1980 was pivotal for the group in three ways. First, Jerry Franklin led a synthesis of our team’s knowledge of old-growth forests, which set the stage for major transformation in public perception and policy toward federal forests a decade later and, incidentally, changed our lives.
A Forest to Prairie Transition as a Long-Term Ecological Research Scientist
Authors: Blair John
Published: November 2020

Being involved in the Long-Term Ecological Research (LTER) program for most of my career has greatly influenced my development as an ecologist. It has broadened my understanding and appreciation of ecological processes at scales ranging from microbial processes to ecosystem fluxes. Participating in the LTER program has heightened my awareness of the critical role of spatial and temporal variability in ecological dynamics, as well as the value of long-term data for identifying directional environmental changes or assessing responses to experimental manipulations. Working with other investigators at an LTER site over long periods of time has revealed the importance of a place-based understanding of ecological processes as a source of insight into complex ecological phenomena. Interacting and collaborating with students and scientists having diverse research interests and backgrounds has enhanced my ability to communicate more effectively with other scientists and with the public. There are some trade-offs between directing a large research program and advancing one’s personal research, but the rewards of long-term collaboration are substantial. I have been part of the LTER program for most of my career, from graduate student at one LTER site to principal investigator at another. I began my PhD training at the University of Georgia in 1983 under the direction of D.A. (Dac) Crossley, Jr., the first leader of the Coweeta (CWT) LTER program. My early research focused on forest ecology, including plant litter decomposition and effects of clear-cutting and regrowth on decomposer communities and forest floor processes (Blair and Crossley 1988). My first postdoctoral appointment was on a National Science Foundation (NSF) grant that I wrote to study forest-floor nitrogen dynamics using stable isotope tracers. In 1992, I joined the faculty of the Division of Biology at Kansas State University as an ecosystem ecologist. This position had been held by Tim Seastedt, another Crossley graduate student who served as principal investigator of the Konza Prairie LTER (KNZ) program and later as principal investigator of the Niwot Ridge LTER program. I was hired with the expectation that I would become engaged in the KNZ program, where my research would focus on ecosystem processes in tallgrass prairie.
The Long-Term Ecological Research Construct for Understanding Dynamics of Coral Reef Ecosystems and Its Influence on My Science
Authors: Schmitt Russell J.
Published: November 2020

The Long-Term Ecological Research (LTER) program facilitated my scientific growth in terms of the questions I can address; the tools, approaches, techniques and data to which I have access; and the diversity of intellectual and disciplinary expertise that I can tap. As a consequence, I am asking questions that cut across much larger spatial and especially temporal scales, and my research projects are more interdisciplinary, complex, and integrated. My ability to mentor students at all levels has been transformed by the variety of resources and opportunities afforded by the LTER program. One consequence is that these students are better prepared to become engaged globally. My role in the LTER program has required me to communicate scientific issues and findings to a broad audience. I have become more interested in the translation of science findings to public policy and practices to help conserve key functions of threatened ecosystems. My involvement with the LTER program has enabled me to forge a much larger circle of national and international collaborators to address questions that require a network of similar sites. The LTER construct has enabled me to broaden the scope of my research by expanding the interdisciplinary nature of my collaborations and the diversity of tools at my disposal. My involvement with the LTER program began in 2000 when I joined the Santa Barbara Coastal (SBC) site as an associate investigator, and it expanded in 2004 to include being the principal investigator of the newly established Moorea Coral Reef (MCR) site. I am privileged to continue to serve as principal investigator of MCR and as an associate investigator at SBC. My research interests center on ecological processes and feedbacks that drive the dynamics of populations and communities. Prior to my involvement in the LTER program, I conducted my research projects either alone or with a small group of like-minded collaborators to address such issues as regulation of (marine) animals with open populations or the effect of indirect interactions on coexistence of species (Figure 28.1). These projects taught me some of the limitations of “small science,” particularly when exacerbated by a lack of relevant long-term data.
Assessing the Paleobiology of the Sunghir People
Authors: Trinkaus Erik , Buzhilova Alexandra P. , Mednikova Maria B. , Dobrovolskaya Maria V.
Published: November 2020

During the Mid Upper Paleolithic, the period of Late Pleistocene human existence within the Interpleniglacial, human foraging populations developed an increasingly sophisticated, elaborated, and complicated existence across Eurasia and probably across most of the Old World. This period of the Paleolithic saw the emergence of various forms of elaborate technology (e.g., ceramics and textiles, as well as elaborations of lithic and organic tool manufacture and use), expanded artistic manifestations, complex social behaviors (especially reflected in personal decoration and mortuary behavior), and increasingly effective and flexible means of subsistence and food processing. For these reasons, the people of this period were referred to, a dozen years ago, as the “Hunters of the Golden Age” (Roebroeks et al. 2000). In those and other assessments of these people, referred to as “Gravettian” in central and western Europe and by other names further east, there is frequent reference to the material from the northern Russian site of Sunghir (Сунгирь; Sungir’). The references to Sunghir are especially to the extremely rich human burials discovered during excavations in 1964 and 1969. The human paleontological materials from Sunghir, however, have only been superficially integrated into the broader assessments of human existence during this time period of hunter-gatherer fluorescence. Several volumes (and innumerable articles) have been written on aspects of the archeological work done at the Sunghir site (e.g., Sukachev et al. 1966; O.N. Bader 1978; N.O. Bader 1998; Seleznev 2008), and there have been two edited volumes concerned principally with the human remains from within and without the burials (Zubov and Karitonov 1984; Alexeeva et al. 2000). However, all of these volumes (as is appropriate) are in Russian, and only the last of them contains extensive English summaries of the contributions. As a result (given the linguistically challenged nature of many Western anthropologists—including one of us), detailed assessments of the Sunghir site and the Sunghir human remains have been slow to permeate the broader anthropological community. Originally, in the 19th century and through much of the 20th century, the focus was on the populational affinities of human remains that emerged from the Upper Paleolithic of Eurasia.
The Ages-at-Death and Sexes of the Sunghir Humans
Authors: Trinkaus Erik , Buzhilova Alexandra P. , Mednikova Maria B. , Dobrovolskaya Maria V.
Published: November 2020

Assessment of the ages-at-death and the probable sexes of the Sunghir humans provides a baseline for their paleobiological evaluation. The former is particularly important for the comparative analysis of the immature Sunghir 2 and 3 skeletons, given the marked changes in size and shape with development. The latter is more important for the adult Sunghir 1, 5, and 6 remains, given some degree of sexual dimorphism among recent humans and apparently within Late Pleistocene early modern humans. In the assessment of age-at-death, it is necessary to evaluate the remains with reference to chronological scales derived from extant human populations of known age (or very recent historical skeletal samples with documented ages). This consideration applies particularly to changes in fibrocartilaginous articulations with age (in this case, a sternal rib end and an auricular surface of Sunghir 1) and to dental calcification during development (for Sunghir 2 and 3). The majority of the data available for these approaches derives from recent European and European-derived (primarily North American) populations, with occasional cross-references to more limited data on recent populations from elsewhere in the Old World. The one exception to this requirement is dental occlusal attrition, for which very general Late Pleistocene (and preindustrial Holocene) reference samples are appropriate, in all cases using scales that are based either on other methods of skeletal aging or employ some version of the “Miles technique” (sequential assessment of dental wear for postcanine teeth as they come into functional occlusion; Brothwell 1981). The determination of sex is most reliable when it utilizes the pelvis, and there is a series of criteria for pelvic sexual evaluation that appear to be universal among recent humans (Brůžek 2002). These dimorphic features mostly appear during adolescence associated with differential lateral development of the pelvis (Coleman 1969; Lavelle 1995). Dimorphic aspects of the greater sciatic notch may appear prior to puberty (Holcomb and Konigsberg 1995; Scheuer and Black 2000), but tests sexing recent human immature skeletons of known sex have provided poor results and tend to identify males more accurately than females (Cardoso and Saunders 2008; Vlak et al. 2008; Wilson et al. 2008).