bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiphoton-Induced Cell Damage
Authors: König Karsten
Published: November 2023

Conventional one-photon fluorescence microscopes employ ultraviolet (UV) and visible (VIS) light sources, such as high-pressure mercury/xenon lamps, the argon ion laser at 364/488/515-nm emission, the frequency-converted Nd:YAG laser at 355/532 nm, and the helium neon laser at 543/633 nm. Typically, the radiation power on the target is some microwatt that corresponds to light intensities in the range of kW/cm2 when focused to diffraction-limited spots by objectives with high numerical aperture (NA > 1). Multiphoton absorption requires higher light intensities.
Nonlinear Multispectral Optical Imaging Microscopy Concepts, Instrumentation, and Applications
Authors: Wachsmann-Hogiu Sebastian , Farkas Daniel L
Published: November 2023

Nonlinear microscopy has made great advances during the past few years, as reviewed throughout this book. Simultaneously, other new approaches to microscopy have proven useful foradvancing its main goals (better resolution, detection, quantitation, and applications), perhaps none more so than spectral microscopy. This chapter examines the confluence of these two areas, reviewing the underlying physics, the instrumentation needed for achieving nonlinear multispectral imaging with microscopic resolution, and some of the interesting applications made possible by these advances in technology.
Cellular Metabolism Monitored by NAD(P)H Imaging with Two-Photon Excitation Microscopy
Authors: Masters Barry R
Published: November 2023

The history, techniques, limitations, and applications of the optical method to monitor oxidative metabolism based on autofluorescence of cells are the subjects of this chapter. In particular, microscopic techniques based on oneand two-photon excitation are compared. The intent is to provide a critical account of the methodology and its limitations, and to describe some of the important applications that are based on two-photon excitation microscopy.
Introduction
Authors: Journel André G , Kyriakidis Phaedon C
Published: November 2023

The problem of evaluation of future recoverable reserves is critical to the mining industry, in that reserves condition both investment and profitability associated with any mining venture. Recoverable reserves relate to a specific area/volume of the deposit, delineated by a mining plan to be economically accessible. This is as opposed to geological (in situ) resources, which refer to the amount of mineral available in the general area to be mined irrespective of whether this amount can be recovered (mined out) economically.
The Simulation Approach
Authors: Journel André G , Kyriakidis Phaedon C
Published: November 2023

This book is not about how to generate or simulate numerical models of a mineral deposit, but about how to use simulated numerical models of the grade spatial distribution for evaluating recoverable reserves.
To Everest, 1951
Authors: Hillary Sir Edmund
Published: November 2023

Riddiford And I, With two of our Sherpas, Pasang and Nyima, arrived in Lucknow on August 28th. We had been instructed to meet Shipton and his party at the railhead of Jogbani on the Indian-Nepalese border, but first we had to purchase stocks of food and fuel. Finding suitable food for Himalayan travel in the bazaars of Lucknow was an almost impossible task, and we ended up with a large amount of bulky and exceedingly expensive tinned food. We loaded all of this and our equipment on to several horse-drawn carts and transported it to the station. Our train wasn’t leaving for an hour, so we started in a rather leisurely way to complete the necessary official formalities entailed in getting all our luggage on the train. We emerged from a fog of utter confusion to realise that the train was leaving in a few minutes and that our luggage was far from being on board. With growing panic we summoned twenty coolies, hoisted the loads on them, and started at a jog-trot for the platform. We swept through the gates just as the guard appeared to blow his whistle. His firm cry of ‘Too Late!’ sounded the death-knell of our plans. But Riddiford was not the man to give in too lightly. His forceful persuasion (and judicious baksheesh) won the day.
Across the Nup La
Authors: Hillary Sir Edmund
Published: November 2023

I Had Always Wanted to attempt the Nup La. In 1951, Riddiford and the others had tried to get up its great icefalls, but had been forced back. Quite apart from the satisfaction of making the first ascent of this formidable pass, George and I had other, more secret, plans. The Nup La is the pass at the head of the Dudh Kosi river and the Ngojumba glacier. On its far side it leads into the West Rongbuk glacier and the northern slopes of Mount Everest. We thought that, if we managed to get over the pass, we’d do a quick trip around the north side of Everest, visiting many of the famous places of the early expeditions and perhaps attempt some climbs. Even to see the face of Everest, that had become so real to us through books and photographs, was an exciting prospect. But first we had to get over the Nup La.

On May 19th George and I left Namche Bazar and climbed up a thousand feet to the village of Khumjung. This was where our Sherpas Angputa and Tashi Phuta lived. We spent the night in Angputa’s house, and were royally entertained by his charming young wife and his aged parents. The Sherpa home is a strongly built and commodious structure. A well-to-do home is of two stories with the walls made of rock plastered together with mud. The roof is usually overlapping slabs of pine with great rocks to hold it all down.
The Swiss Attack
Authors: Hillary Sir Edmund
Published: November 2023

For Two Days We rested beside a little lake near the Ngojumba glacier. It was calm and peaceful here, and we slept almost continuously. We had obtained some fresh food, and we ate enormous meals of potatoes and butter and yak curds. But we couldn’t keep the old question out of our minds. ‘What did the Swiss do?’ It was now June 5th, and they should be coming off the mountain with their story of success or failure. We decided to go and see them and find out for ourselves.

Between us and the Khumbu glacier was a high pass. This had been crossed from east to west in 1951, and we planned to use it. On June 6th we moved off from our rest-camp and crossed the Ngojumba glacier to the side glacier leading up to the pass. There were six of us altogether – George and I, Angputa and Tashi Phuta, and two tough old specimens we’d recruited down the valley, Pemba and Angpemba. Angje had gone directly down to Namche Bazar with all our excess gear. On the side glacier – the ‘Guanara’ the Sherpas called it – we found a pleasant and easy route in the trough behind the left-hand moraine wall. It was a quiet and protected place, and the flowers were blooming in profusion. The air was warm and heavy, but George set a cracking pace. We soon drew well away from the Sherpas, so stopped in a grassy hollow and slept for an hour in the sun.
Camp Nine
Authors: Hillary Sir Edmund
Published: November 2023

I Awoke With The feeling that something was wrong. It took me a moment to understand what it was, and then I realised that everything was deathly quiet – the wind had dropped completely. And then I heard it approaching again like an express train emerging from a tunnel, and soon the tent was rocking and wrenching in familiar fashion. But the fact that the wind had stopped, even for a moment, was the first hopeful sign we’d had since I’d reached the South Col. I glanced at my watch – it was just after four o’clock, so I stirred Tenzing, and we started our long, slow preparations for breakfast. By 7.30 the wind had started to ease a little, and I crawled out of the tent and conferred with Lowe and Gregory in the Pyramid. We decided to start. All six of us were to carry substantial loads of oxygen, food, and equipment, and the previous day we’d carefully made them up so as not to have a pound of unnecessary weight. I was checking oxygen loads when a shout from George Lowe attracted my attention, and he came over to me with a very worried look on his face. Apparently Pemba had been ill all night and didn’t feel capable of leaving.
Inventing Barriers
Authors: Mcdonagh Eileen , Pappano Laura
Published: November 2023

How many times have you gotten into a cab, met a friend for dinner, or had a drink with colleagues after work, and found yourself opening the conversation with an observation about sports? Sports facts figure into speech patterns designed to connect strangers or set the scene for greetings among friends, much as do facts about the weather. Even those who eschew an interest in sports get drawn into the fray. When one author’s son moved from Boston to New York, he reported that people constantly observed, “Gee, it must be hard to be a Red Sox fan and live in New York.” The assumption was that the most salient difference between living in Boston and the Big Apple must be sports loyalties (even if it wasn’t). The power of sports talk is nowhere more evident than on sports radio, where fans tune in to confirm their allegiance to the home team, express their views on the decisions of management or player performance, and boost their commonality. Discussions are often detailed, including talk of salary caps, draft pick strategies, and injury reports. Nonetheless, there is a remarkable myopia to these conversations, which utterly fail to acknowledge the meaning of sports. Sports policies can be used to construct—and deconstruct—race and sex hierarchies. As such, sports is much more than facts; it is also an arena for establishing—or challenging—the meanings associated with race and sex differences.
Evolutionary Developmental Biology
Authors: Stern David L
Published: November 2023

Evolutionary developmental biology (EDB, often shortened to “evo-devo”) includes a broad array of studies, stretching from phylogenetic analysis of developmental genes to comparative studies of embryos and gene expression patterns to microevolutionary studies of the genetic basis for morphological change. This is a partial list and, in general, studies that attempt to combine evolutionary and developmental studies have been placed under the heading of EDB. While the field is broad and rich, I attempt in this chapter to highlight a few important conceptual findings in EDB. This brief summary will, of necessity, omit many exciting avenues of research that fall under the umbrella of EDB. Nonetheless, I believe there is a coherence to EDB studies that is reflected in the broad conceptual strokes I outline in this chapter. For example, the major finding of EDB has been the discovery that many of the genes controlling animal development are conserved across wide phylogenetic expanses.
Four, Two, or One? Gordon Allport and the Unique Personality
Authors: Barenbaum Nicole B
Published: November 2023

Arecurrent theme in the work of personality psychologist Gordon Allport (1897–1967) is the opposition between the general and the unique in psychology (e.g., Allport, 1962a). In a characteristic statement of this theme, Allport described in neutral terms two tendencies in human thought: “The mind may classify its experience and contemplate the general principles that emerge, or it may be concerned with the individual happening or single event confronting it “ (1942, p. 53). To illustrate these tendencies, however, he quoted from William James, choosing a passage that was far from neutral: The first thing the intellect does with an object is to class it along with something else. But any object that is infinitely important to us and awakens our devotion feels to us also as if it must be sui generis and unique. Probably a crab would be filled with a sense of personal outrage if it could hear us class it without ado or apology as a crustacean, and thus dispose of it.
Nietzsche ‘s Madness
Authors: Arnold Kyle , Atwood George
Published: November 2023

At first glance, a psychobiographical study of Nietzsche might appear inherently naive. After all, weren ‘t Nietzsche ‘s writings partly responsible for what literary theorists call the “death of the author, “ the current tendency of many scholars to dismiss any connection between an author ‘s subjectivity and his or her work? Doesn ‘t this imply that Nietzsche ‘s work also announced the “death “ of psychobiography (Sarup, 1993)? Perhaps. Yet as we so often find when examining Nietzsche ‘s texts, these strands of thought are interwoven with their polar opposites. Nietzsche ‘s apparent flight from the notion of alldetermining authorship is coupled with a desire to reconnect text with author, to use the lived experience of authors in rescuing their texts from what he saw as the thin, unbreathable air of impersonal and bloodless intellectuality. Philosophical ideas, for instance, are envisaged as “hav[ing] always lived on the ‘blood ‘ of the philosopher, they always consumed his senses and even, if you will believe us, his ‘heart.
Phage and the Early Development of Molecular Biology
Authors: Summers William C
Published: November 2023

Molecular biology evolved from multiple origins including the antivitalist biology of the early twentieth century which attempted to explain complex biological phenomena in terms of physical and chemical phenomena (16, 21), the Rockefeller Foundation program, led by physicists and mathematicians who believed the ‘‘human sciences’’ were ripe for deeper understanding based on chemistry and physics (29), research by physicists and chemists who saw life as a challenge to their burgeoning understanding of the fundamental structure of matter (2, c22), and work by a few microbiologists and geneticists who sought better understanding of the natures of genes and microbes (23).
Prophage Genomics
Authors: Brussow Harald
Published: November 2023

At the time of this writing, the GenBank phage database comprises 200 complete phage genome sequences. An equivalent number of phage sequences were passively acquired as prophages in bacterial genome sequencing projects. The scientific value of these prophage sequences was only recently recognized (13, 14). It goes beyond their potential to double the content of the current phage database and to correct a bias of the database towards selected phage systems (coliphages, dairy phages, mycobacteriophages) (7, 9). These prophage sequences allowed a first insight into the evolution of phage^host genome interactions at a molecular level. This analysis turned out to be especially fruitful for bacterial pathogens (1, 5, 49).
Evolution of Tailed Phages: Insights from Comparative Phage Genomics
Authors: Brussow Harald , Desiere Frank
Published: November 2023

Many phage researchers believe that phages are as old as their bacterial hosts. If this hypothesis is true, then we have to postulate elements of vertical evolution for phages. In view of the postulated antiquity of these relationships we might not expect sequence similarities between more distantly related phages. Comparative phage genomics can reveal DNA sequence, protein sequence, or gene map similarities in the absence of sequence similarities between increasingly diverged phages. For even more distant relationships, data from structural biology can be informative. Recent genomics-based ideas on phage evolution are dominated by two interpretations. In one view all doublestranded DNA tailed phage genomes are mosaics with access, by horizontal exchange, to a large common genetic pool, but in which access to the gene pool is not uniform for all phages (22). In this hypothesis horizontal gene transfer dominates over vertical evolution. In fact, it is in some way an updated version of the classical modular theory of phage evolution developed 30 years ago on the basis of heteroduplex mapping with lambdoid coliphages (2, 7). Other investigators studying phages from dairy bacteria observed strong elements of vertical evolution in the structural gene cluster of phages that were not erased by horizontal gene transfer events (5).
Gene Regulatory Circuitry of Phage
Authors: Little John W
Published: November 2023

The gene regulatory circuitry of phage l was the first complex regulatory circuit to be analyzed in molecular detail. l was chosen as a model system for this purpose because it displays a wide range of interesting regulatory properties. It can adopt two alternative life-styles, the lytic and lysogenic states, and it can switch from the lysogenic state to the lytic state in the process of prophage induction, often called the ‘‘genetic switch’’ (13, 28). A choice is made between these two alternative pathways soon after infection; the lysogenic state, in particular, is highly stable, and the switch can be highly efficient. It was clear early on that these properties would be of general relevance to other organisms, including higher eukaryotes.
Lipid-Containing Bacteriophage PM2, the Type Organism of Corticoviridae
Authors: Bamford Dennis H Bamford Jaana K H
Published: November 2023

Bacteriophage PM2 is the only described member of the Corticoviridae family (1). It was isolated from seawater collected from a polluted bay off the coast of Chile (13). The original host was a common marine bacterium Pseudoalteromonas espejiana BAL-31 (originally Pseudomonas BAL-31; 14, 18), which is the source of the DNA exonuclease BAL-31. Alternatively, Pseudoalteromonas sp. ER72M2 obtained from the East River, New York, by Leonard Mindich (26) can be used as a host for PM2. PM2 is the first bacteriophage in which the presence of lipids in the virion was firmly demonstrated (7, 15). The mass of the virion ( 4.5 107 Da) is distributed among nucleic acid (14%), lipid (14%), and protein (72%) constituents (8, 9). The sedimentation coefficient (S20,w) of the particle is 293 S and buoyant density in sucrose and cesium chloride is 1.26 g/cm3 and 1.28 g/cm3, respectively (8, 26). The stability of the virion is dependent on sodium and calcium ions and the virion equilibrated in sucrose is inactive (26).
Bacteriophage SPP1
Authors: lurz Juan C Alonso paulo tavares rudi , Trautner Thomas A
Published: November 2023

The lytic Bacillus subtilis bacteriophage SPP1 was isolated in Pavia (Subtilis Phage Pavia) and first described by Riva et al. (99). Interest in this phage derived at first from the observation that the complementary DNA strands of the phage were separable into a heavy strand (r 1.725 g/cm3) and a light strand (r 1.713 g/cm3) following denaturation and isopycnic centrifugation (99, 109). This observation and the finding that the phage was highly active in transfection led to the use of SPP1 in studies of mismatch repair (109). In later experiments the molecular biology of the phage, including its structure, total DNA sequence, genetics, and life cycle were established.
N15: The Linear Plasmid Prophage
Authors: Ravin Nikolai V
Published: November 2023

The temperate bacteriophage N15 is unique among Escherichia coli phages in that its prophage is not integrated into the bacterial chromosome but instead is a linear plasmid molecule with covalently closed ends. Linear plasmids are very unusual in the Enterobacteria and only two others have been reported: phiKO2 in Klebsiella oxytoca (4, 43) and pY54 inYersinia enterocolitica (16). However, such replicons are common in the spirochete genus, Borrelia (1). Here I will summarize the most relevant work on phage N15 with a special emphasis on the mechanism of replication, telomere formation, and control of lysogeny.
Phages of Cyanobacteria
Authors: Mann Nicholas H
Published: November 2023

The scientific importance of the phages of cyanobacteria (cyanophages) is intimately associated with the ecological significance of their hosts. Cyanobacteria are arguably the most diverse and widely distributed group of eubacteria on the planet and play central roles in major biogeochemical processes, such as the carbon and nitrogen cycles. Cyanobacteria exist in a wide range of freshwater and marine environments, ranging from thermophilic to psycrophilic, and terrestrial environments, including those subject to periodic desiccation. By virtue of their higher plant-like oxygenic photosynthetic apparatus they contribute significantly to the maintenance of the Earth’s atmosphere, in terms of both oxygen production and carbon dioxide fixation. Consequently, the ability of cyanophages to determine the population structures and genetic diversity of cyanobacteria, as well as to potentially influence the dynamics of biogeochemical processes, gives them a unique ecological significance.
Yersinia Phages
Authors: Appel Stefan Hertwig Mikael Skurnik Bernd
Published: November 2023

The genus Yersinia contains 11 species, of which Yersinia enterocolitica,Yersinia pestis, and Yersinia pseudotuberculosis are pathogenic for humans and animals (5). While Y. pestis is the causative agent of plague, Y. enterocolitica and Y. pseudotuberculosis are mainly enteropathogenic. In comparison with the other pathogenic Yersinia species, Y. enterocolitica is very heterogeneous, comprising pathogenic and nonpathogenic strains which belong to about 70 serogroups. In order to differentiateYersinia strains, a number of phages were isolated and used for typing. Several phage typing sets have been worked out for Y. enterocolitica (4, 30, 38). The sets contain temperate phages isolated from Yersinia strains (37, 39) or phages isolated from sewage (2, 8), whose origin is unknown. Three yersiniophages have been sequenced: phages fA1122, fYeO3-12, and PY54. This chapter is primarily an overview of the properties of those three phages.
Phages of Lactococcus lactis
Authors: Hammer Lone Brąndsted Karin
Published: November 2023

Lactococci are Gram-positive mesophilic bacteria with low G-C content that belong to the group of lactic acid bacteria. They are aerotolerant and live by means of fermentation, as they are lacking a respiratory chain, and the main end product during fermentation is lactic acid. In nature lactococci are mainly found on plant material (100). Some lactococci have apparently adapted to multiply in milk and contain a plasmid-encoded milk protease and enzymes responsible for catabolism of lactose. Lactococcus lactis is used world-wide as starter culture for large-scale milk fermentations producing cheese such as cheddar and other fermented milk products. It has been estimated that approximately 107 tonnes of cheese are made annually, leading to human consumption of close to 1018 lactococci (41). In the genus Lactococcus five species are currently found: L. lactis, L. garviae, L. plantarum, L. piscium, L. raffinolactis (101, 118).
The Use of Phage as Diagnostic Systems
Authors: Rees Cath
Published: November 2023

The most common use of bacteriophage in detection methodology is phage typing. When developing panels of phage which will discriminate between isolates of the same species on the basis of lytic spectrum, phage are chosen specifically because of their narrow (and there-fore discriminatory) host range. Since this is the use of phage most commonly encountered, a general impression has been created that phage have a narrow host range. Hence, one of the most commonly voiced criticisms of phage-based detection methods is that the host range of phage - and therefore any test - is limited, but this is far from the truth. When phage are selected for detection of species or of whole genera, those with the widest host range are chosen. A classic example of this is the phage Felix 01, first described as a broad-host-range phage infecting Salmonella enterica by Cherry et al. (8).
Diagnosing Depersonalization Disorder
Authors: Simeon Daphne , Abugel Jeffrey
Published: November 2023

Like any other psychiatric condition, the diagnosis of depersonalization disorder (DPD) is made clinically, by meeting with the patient and conducting a thorough evaluation interview. Descriptions of the symptoms, as we have described throughout this book, and as spelled out in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), serve as the point of departure—symptoms that are not just fleeting, but recurrent or persistent. The symptoms must also not be occurring exclusively and only in the context of some other condition, be it psychiatric, medical, or related to substance use. If, for example, the depersonalization happened only when the person was deeply depressed, or during a panic attack, or a seizure, or because a person has a brain tumor, he or she would not be diagnosed as having DPD. Likewise, regular substance users (daily drinkers or marijuana users) who experience depersonalization only in that context would not be diagnosed with DPD.
The Blow of the Void: Depersonalization in Literature and Philosophy
Authors: Simeon Daphne , Abugel Jeffrey
Published: November 2023

The idea that reality is subjective, constructed from our own perceptions, is quite an ancient concept. “We are what we think. All that we are arises with our thoughts. With our thoughts, we make the world,” said the Buddha. Depersonalization, a serious disruption in a person’s thoughts or sensations about their individual self, understandably alters their entire world. A person may feel as if everything he or she has ever believed must be somehow reconstructed back to what it was, or made afresh, since little of what was once taken for granted remains solid or safe. People may find themselves in a Never Neverland with an altered sense of self, or a distinct sensation of having no self at all. Struggling with this mental change can lead down many paths, sometimes implying a spiritual awakening, while at other times the path may lead to anxiety, fruitless rumination, and, on occasion, works of art.
Introduction
Authors: Becker Jasper
Published: November 2023

The fictional scenario that follows is based on the notion that one day the United States might launch an attack in order to enforce international law and prevent North Korea from acquiring, selling, and using its weapons of mass destruction. This very nearly happened in 1994, and as President George Bush warned in 2001, this remains a possibility.
Kim Jong Il—The Terrorist Master
Authors: Becker Jasper
Published: November 2023

When a mysterious vessel was spotted lurking close to Japan’s shores in 2001, a naval patrol gave chase. When the intruder refused to stop, there was a brief fire fight, and the vessel sank to the bottom of the sea. Later the Japanese navy managed to raise it and put it on public display in 2002. To any casual observer it looked like an ordinary fishing boat, but up close it was possible to see that it was heavily armed with weapons that included a surface-to-air missile launcher. Closer examination revealed that a special door fitted into the hull could open to release a tiny submersible scooter big enough to carry three men for a few miles. It enabled special agents to sneak ashore undetected.
Nuclear Warlord
Authors: Becker Jasper
Published: November 2023

The plan to bomb North Korea’s nuclear facilities seemed simple. President William Clinton sat with his advisers in the West Wing as his Defense Secretary William J. Perry laid out satellite photographs of North Korea’s plutonium reprocessing facility. They showed a long narrow two-story fac-tory next to a small experimental reactor at Yongbyon, some 60 miles north of Pyongyang. A wave of cruise missiles and F-117 stealth fighters flying high beyond the reach of the North’s air defenses dropping laser guided bombs could easily blast it.
Kim Jong Il—The Reformer
Authors: Becker Jasper
Published: November 2023

The first executions in Songrim City took place at nine o’clock one morning in February 1998. A truck carrying five condemned men, all senior executives of the Hwanghae Iron and Steel Works, all blindfolded, bound, and dressed in thick padded cotton clothing, halted before the crowd of steel workers and their families who had been summoned to watch. As the guards pulled the prisoners off the truck the crowd noticed that the men were limping so badly that the guards had to half drag each of them to the execution posts erected on the municipal sports ground.
Grappling with a Rogue State
Authors: Becker Jasper
Published: November 2023

U.S. Secretary of State Madeleine Albright was in Pyongyang in the last months of the second Clinton Administration holding talks with Kim Jong Il when he announced he had prepared a special surprise for her. That evening they arrived at the May Day Stadium for a performance by 100,000 citizens, which Kim confided would help the Americans understand North Korea. A huge crowd gave forth a volcano of rapturous sounds as they arrived. “It began with a giant image of a hammer for workers, a brush for intellectuals, and a sickle for farmers.
Huntington’s Disease
Authors: Ogden Jenni A
Published: November 2023

Huntington’s disease is the focus of one of the most remarkable stories of discovery in medical history. In 1872, George Huntington, a North American general practitioner, published the first unambiguous description of this unrelenting neurodegenerative disorder in The Medical and Surgical Reporter (Huntington 1872). The title of his article was simply “On Chorea,” and his description of this type of chorea as a specific hereditary disorder became quickly and widely accepted and became known as Huntington’s disease (HD). HD is a chronic, progressive hereditary disease, usually of adult onset, and is typified by a number of motor abnormalities, most obviously the excessive, spontaneous irregular movements called chorea, but also other motor disorders such as rigidity. Accompanying these motor disorders is a range of psychiatric, behavioral and cognitive disturbances and a progressive decline to a severe dementia is almost inevitable if the patient lives long enough.
Dementia
Authors: Ogden Jenni A
Published: November 2023

In most Western countries, the proportion of elderly to young in the population is increasing rapidly because of the dual factors of improving health care, leading to longer life expectancy, and decreasing family size. The incidence (number of newly diagnosed cases) of dementia rises with increasing age and exceeds one new case per 100 in the 70–80 age group and two new cases per 100 in the over 80 age group. As patients with dementia tend to live for a number of years, the prevalence (total number of sufferers in a specified population at any one time) is higher than the incidence. The prevalence of dementia doubles every 5 years after the age of 60 years. In the age bracket 60–65 years, 1% have dementia, and in the age bracket 85 years and older, 35%–40% suffer dementia (Hendrie 1998). Therefore, the number of elderly people with dementia that the population must support is increasing dramatically (McLean 1987a). In 1999, the World Health Organization estimated that there were 20 million people suffering from dementia (of all types) worldwide, a figure estimated to reach 40 million by 2025, and that 66% of these dementia victims live in developing countries (Richter and Richter 2002; Walker and Salek 2002).
Fitting data with linear regression
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

Linear regression can be viewed as just a special case of nonlinear regression. Any nonlinear regression program can be used to fit to a linear model, and the results will be the same as if you had chosen linear regression. Because linear regression is usually performed separately from nonlinear regression, we explain linear regression separately here.
Interpreting the results of linear regression
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

Linear regression finds the best-fit values of the slope and intercept, and reports these values along with a standard errors and confidence intervals. The standard error values of the slope and intercept can be hard to interpret intuitively, but their main usefulness is to compute the 95% confidence intervals. If you accept the assumptions oflinear regression, there is a 95% chance that the true value of the slope lies within the 95% confidence interval of the slope. Similarly, there is a 95% chance that the true value of the intercept lies within the 95% confidence interval of the intercept.
Tips on choosing a model
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

In many cases, picking a model will be easy, as you will likely be choosing a model that is conventionally used in your field. Later in the book, we discuss in detail some of the models commonly used in experimental biology. If you aren’t sure about the model, take the time to learn. If you pick a model that isn’t right for your experimental situation, the regression results won’t be helpful.
Unequal weighting of data points
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

As outlined in the previous chapter, regression is most often done by minimizing the sum­ of-squares of the vertical distances of the data from the line or curve. Points farther from the curve contribute more to the sum-of-squares. Points close to the curve contribute little. This makes sense, when you expect experimental scatter to be the same, on average, in all parts of the curve.
Testing whether a parameter differs from a hypothetical value
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

The approaches for comparing models described in the previous chapters can also be used to perform statistical testing on individual model parameters. The key is to recast the problem as a choice between two models, one where the parameter of interest is estimated, and another where the same model is refitted to the data with the parameter of interest constrained to a specified value. This concept is illustrated with an example below. The null hypothesis is that the standard Hill slope of 1.0 is correct. To fit the model corresponding to the null hypothesis (simpler model), you constrain the slope to equal 1.0; you are thus fitting a three-parameter Hill equation (Top, Bottom, and LogEC50 being estimated). The alternative hypothesis is that the Hill slope has some other value. To fit this model, fit the variable slope sigmoidal dose-response curve equation (also called a four-parameter Hill equation). The program will find best-fit values of Top, Bottom, LogEC50 and HillSlope. For these data, the best-fit Hill slope is 0.7535.
Using a paired t test to test for a treatment effect in a series of matched experiments
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

Chapter 25 explained how to compare two curves obtained in one experiment. But if you really want to know how a treatment changes the parameters of a curve, you’ll want to repeat the experiment several times. This chapter explains how to pool the results from several experiments. The first step is to focus on what you really want to know. In most cases, you’ll care most about a best-fit parameter from curve fitting.
Analyzing radioligand binding data
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

A radioligand is a radioactively labeled drug that can associate with a receptor, transporter, enzyme, or any site of interest. Measuring the rate and extent of binding provides information on the number of binding sites, and their affinity and accessibility for various drugs. There are three kinds of experimental protocols for radioligand binding, discussed in the next three chapters.
Complex dose-response curves
Authors: Motulsky Harvey , Christopoulos Arthur
Published: November 2023

The standard (Hill) sigmoidal dose-response model is based on the assumption that the log(dose) vs. response curve is symmetrical around its midpoint. But some dose-response curves are not symmetrical. In a recent study, Van der Graaf and Schoemaker (J. Pharmacol. Toxicol. Meth., 41: 107-115, 1999) showed that the application of the Hill equation to asymmetric dose-response data can lead to quite erroneous estimates of drug potency (EC50). They suggested an alternative model, known as the Richards equation, which could provide a more adequate fit to asymmetric dose-response data. Here is the Richards model shown both as an equation and as computer code.
The Parkinson’s Disease Treatment Book
Authors: Ahlskog J Eric
Published: November 2023

Over 4 million people worldwide and 1 in every 500 people in the UK, suffer from Parkinson's Disease. Now, a leader in the fight against Parkinson’s, Dr. J. Eric Ahlskog of the Mayo Clinic, has written the definitive guide for patients and their families. Dr. Alhskog offers a crystal-clear, nuts-and-bolts approach to the treatment of PD, distilled from over twenty years of experience as a clinician and researcher. His goal is to educate the patient so that they can better team with their doctor to do battle with the disease, streamlining the decision-making process and enhancing their treatment. To do this, Dr. Ahlskog offers a gold mine of information: How do I know if I have PD? What kinds of tests can I take? What medications slow the progress of the disease? What if medications don’t help my tremor? What kinds of movement problems may develop later? How can I cope with insomnia and daytime sleepiness, dizziness and depression, memory problems, paranoia, and delusions? Indeed, the book covers virtually every topic related to Parkinson’s, from sexual impotence and skin rashes, to the role of nutrition, exercise, and physical therapy. In addition, Dr. Ahlskog discusses brain surgery (though he urges that patients only consider this as a last resort) and such experimental therapies as stem cell transplantation and gene therapy. There are also lists of support and advocacy groups and Internet sites that focus on Parkinson’s. The ultimate guide to symptoms and treatment, this superb book is the first place patients should turn for reliable, easy-to-grasp information on Parkinson’s disease.
Background and Rationale
Authors: Ahlskog J Eric
Published: November 2023

Parkinson’s disease (PD) is a treatable condition. Medical treatment increases longevity and allows most people with PD to remain active and productive for many years. We don’t have a cure (yet), but some of the responses to available drugs are striking and occasionally border on the miraculous. PD is one of the most treatable of all neurological conditions. The medical treatment of PD, unfortunately, is not always simple. There are multiple medications and they can be used in a variety of ways. The choice of the drug, the dose, and the timing often are crucial; therapy must be individualized to meet each person’s unique requirements. Also, the distinction between PD symptoms and medication side effects frequently causes confusion, with potential for ineffective or inappropriate treatment. Sometimes, treatable symptoms are not even recognized as part of PD. The difference between optimal versus ineffective therapy may be the difference between a nursing home and independent living. The goal of this book is to help each and every person with PD achieve the best treatment.
How Do I Know If I Have Parkinson’s Disease?
Authors: Ahlskog J Eric
Published: November 2023

The diagnosis of Parkinson’s disease (PD) is not always simple. Even seasoned physicians may be troubled by certain cases. For the person with PD, recognizing that something is wrong may take months. The onset is insidious and symptoms may blend into the routine. Although tremor may provide a clear signal, many people do not experience this as one of their initial symptoms. Some of the manifestations of PD may be so subtle and nonspecific that they are not even appreciated as being abnormal. For example, they may be written off to age: “Of course I’m slowing down; I’m getting older.” Or some other explanation may seem plausible: “I walk bent over because my back hurts.” On the other hand, certain signs may be incorrectly attributed to PD. Not all tremor represents PD, and in fact the majority of people with tremor do not have PD. Parkinson’s disease is a clinical diagnosis made in the doctor’s office. The story plus examination findings provide the evidence. There are no laboratory tests that identify PD. The tests are primarily for the purpose of excluding other disorders and are often not needed (see chapter 7 on testing). In this chapter, we focus on the clinical clues that point us to the diagnosis.
Thinking, Memory, and Dementia
Authors: Ahlskog J Eric
Published: November 2023

Parkinson’s disease (PD) is primarily a disorder affecting movement, but memory, judgment, and thinking may become impaired in some cases. The physician’s term for thinking, judgment, and memory is cognition. When impairment of cognition is substantial, irreversible, and interfering with activities of daily living, we term this dementia. Dementia may complicate otherwise typical PD, representing progression of the disease process. When this has been assessed in PD clinics, it is found in a minority of patients and usually late in the course. Thus, just because you have PD does not mean that you are destined to become demented. Moreover, not everyone with PD who complains of memory impairment is demented. There are other reasons why thinking and memory may be affected. Let’s consider this in more detail.
Treating Other Problems: Swelling, Skin Rashes, and Visual Symptoms
Authors: Ahlskog J Eric
Published: November 2023

Several other conditions are common in Parkinson’s Disease (PD) that require treatment other than levodopa and related drugs. In this chapter we will address three problems that frequently develop in the context of PD: swollen legs, certain skin rashes, and visual distortions or blurring. Swelling of the legs is common among seniors in general. It is particularly common among seniors with PD but sometimes occurs in younger people with PD as well. People often worry that swelling is caused by poor circulation to their legs. Rather, it is often just the opposite; it results from poor circulation from the legs. Let’s briefly define terms so that we can consider this in more detail. Arteries carry blood with oxygen and nutrients to the major organs, muscles, skin, and so on. After the oxygen and nutrients have been extracted, the blood flows back to the heart via the veins.
Family, Friends, the Workplace, and Caregivers
Authors: Ahlskog J Eric
Published: November 2023

Should your PD diagnosis be disclosed to friends and family? Clearly your spouse needs to know, and rarely are there exceptions to this axiom. Disclosure beyond that, however, is a personal choice and depends on circumstances. Let’s think about some of the factors that weigh in this decision. If your PD is well controlled and you are experiencing no compromise of activities, it is not necessary to reveal the diagnosis. The PD medications are often effective in abolishing the signs of PD; others may not notice that anything is wrong. You may feel more comfortable not talking about your diagnosis of PD and that is perfectly fine. Sometimes it is easier to downplay the illness and focus on the positives in life. For some, it is important to talk about PD. Perhaps your sense of immortality has been shattered by the prospect of a chronic disease; if the mental burden weighs on your mind, then by all means, share this with appropriate friends and family. Talking about things that bother us helps make peace with ourselves and confront our shortcomings.
The Structure of Daily Positive Affect for Persons With Parkinson’s Disease: A Dynamic Factor Analysis
Authors: Shifren Kim , Hooker Karen
Published: November 2023

There is an impressive literature on the positive aspects of living with chronic diseases such as diabetes mellitus, multiple sclerosis, coronary heart disease, and various forms of cancer (Benyamini, Idler, Leventhal, & Leventhal, 2000; Fournier, deRidder, & Bensing, 2003; Reich, Zautra, & Davis, 2003; Symister & Friend, 2003). Though this body of literature had been steadily growing since 1990, it increased substantially after the introduction of positive psychology (e.g., Peterson, 2000). Researchers interested in any aspect of the positive side of individuals and how they deal with illness and other negative life events have been encouraged to conduct studies that do not focus solely on the negative side of coping processes and outcomes. In fact, researchers have found that state-positive affect (i.e., short-term positive affect) is related to health while trait-positive affect is not (Casten, Lawton, Winter, Kleban, & Sando, 1997). Researchers have also discussed the adaptive functions of positive affect (PA) in the coping process, especially when dealing with chronic stressors (Folkman & Maskowitz, 2000).
Understanding Individual and Age Differences in Well-Being: An Experimental Attention-Based Approach
Authors: Isaacowitz Derek M
Published: November 2023

The idea that there may be important links between thinking and feeling is not a new one. In clinical psychology, Beck’s influential theory of depression asserted that dysfunctional cognitions represent not just a symptom of depression, but rather a cardinal cause of the disorder itself. In the social cognitive study of emotion, links to cognition have been at the core of several controversial assertions. For example, the longstanding debate between Zajonc (1980, 1984) and Lazarus (1982) centered on whether cognition does or does not necessarily precede emotion. Additionally, Bower’s (1981) network theory made important assertions concerning the contextual links between emotional experience and memory. Only more recently, however, have researchers interested in the links between emotion and cognition turned from focusing either on the necessity of cognition for emotion or on the effects of emotion on memory to ask more refined questions about where and how emotion might affect cognition. In particular, rather than viewing information processing as a black box and using only memory measures to determine simply whether cognition had been impacted somehow by emotion, researchers have attempted to decompose information processing into more specific parts to better understand where the “action” may be linking emotion with processing of stimuli from the environment.
Multilevel Modeling of Motivation: A Self-Determination Theory Analysis of Basic Psychological Needs
Authors: Brown Kirk Warren , Ryan Richard M
Published: November 2023

Motivation is, by its very nature, a dynamic process. Human motives and desires fluctuate in direction and strength according to inner promptings and environmental contingencies that can facilitate or inhibit the satisfaction of needs, and desires also vary as individuals negotiate their day-to-day lives. This dynamic character of motivation has implications for research designs and analytic approaches used to investigate it. Because traditional one-occasion, experimental, and longitudinal approaches typically provide very limited opportunities to model the dynamic variability of motivation, researchers have begun to pair nontraditional methods such as experience sampling with analytic tools such as multilevel modeling to extend our understanding of motivation as it operates in day-to-day contexts. In this chapter, we discuss recent research using multilevel approaches to modeling the variable nature of motivation and its consequences. Specifically, we focus on recent efforts to understand the expression of three basic psychological needs specified by self-determination theory (SOT; Oeci & Ryan, 2000; Ryan, 1995).
About Suicide Notes
Authors: Shneidman Edwin S .
Published: November 2023

Collections of suicide notes have been available since the middle of the nineteenth century. Some writings about suicide notes typically have been anecdotal; others have been collections of notes without comment. As the reader already knows, my study of suicidal phenomena began in 1949 with my discovery of hundreds of suicide notes in the vaults of the Los Angeles County Coroner’s office.
Consultation By Morton Silverman, M.D.
Authors: Shneidman Edwin S .
Published: November 2023

This report might be called “The Man Who Knew Too Much.” I approach the study of an individual’s self-injurious death as a mystery that needs to be solved. Was it truly a suicide? Why was it a suicide? Does it “make sense” to me? Is it understandable? Often we are not left with much to study, other than the bare facts of the death and reports by police and medical examiners. In a relatively small minority of the cases a suicide note is left behind. So there is often much speculation about intent, motives, predisposing factors, and precipitating events.