Around one third of all biologically relevant small molecules are organic cations. These include endogenous substances like catecholamines and other neurotransmitters, toxins and drugs designed to affect signaling processes. The organic cation transporter 1 (OCT1) is among the strongest expressed membrane transporters at the sinusoidal (blood-facing) side of liver cells and contributes substantially to the clearance of the blood from numerous organic cations. A most striking feature of OCT1 is its pronounced genetic diversity. Between 1 and 10% of all human populations have little to no OCT1 activity. With several of the OCT1 substrates up to 10% of Europeans are functionally OCT1 deficient. Apparently, the lack of OCT1 do not lead to apparent substantial pathological changes in these individuals. It thus appears that this transporter is not essential to human life, but does it means that OCT1 is irrelevant? In the last 25 years since the first cloning of this transporter, data on its pharmacological and physiological relevance is steadily accumulating. Numerous clinically relevant drugs (e.g. metformin, morphine, fenoterol, sumatriptan, tramadol and tropisetron) have been shown to be substrates of OCT1, and OCT1 deficiency has been shown to affect the pharmacokinetics, efficacy, or toxicity of these drugs. Also vitamin B1 has been shown to be a substrate of OCT1, and in genetically modified mice OCT1 substantially modulated hepatic lipid metabolism, total body fat and systemic glucose and lipid concentrations. Still, numerous important questions remain unsolved: For which drugs, toxins, or other endogenous or exogenous substances is OCT1 relevant? How can we predict the relevance of OCT1 from in vitro studies? What determines the substrate selectivity of OCT1 in comparison to other transporters or transport processes for organic cations? What regulates the expression of OCT1 in the liver and possibly in other tissues? What is the impact of OCT1 variation in different areas of medicine, including the therapies for cancer as well as for pulmonary, cardiovascular, or neurological diseases? How can evolutionary biology contribute to a better understanding of the roles of OCT1? And, importantly, what types of research are likely to significantly further the knowledge on OCT1 in the next decades?

How dull plays are killing theatre and what we can do about it. Had I become disenchanted with the form I had once fallen so madly in love with as a pubescent, pimple-faced suburban homo with braces? Maybe theatre was like an all-consuming high school infatuation that now, ten years later, I saw as the closeted balding guy with a beer gut he’d become. There were of course those rare moments of transcendencethat kept me coming back. But why did they come so few and far between? A lot of plays are dull. And one dull play, it seems, can turn us off theatre for good. Playwright and theatre director Jordan Tannahill takes in the spectrum of English-language drama – from the flashiest of Broadway spectacles to productions mounted in scrappy storefront theatres – to consider where lifeless plays come from and why they persist. Having travelled the globe talking to theatre artists, critics, passionate patrons and the theatrically disillusioned, Tannahill addresses what he considers the culture of ‘risk aversion’ paralyzing the form. Theatre of the Unimpressed is Tannahill’s wry and revelatory personal reckoning with the discipline he’s dedicated his life to, and a roadmap for a vital twenty-first-century theatre – one that apprehends the value of ‘liveness’ in our mediated age and the necessity for artistic risk and its attendant failures. In considering dramaturgy, programming and alternative models for producing, Tannahill aims to turn theatre from an obligation to a destination. ‘[Tannahill is] the poster child of a new generation of (theatre? film? dance?) artists for whom "interdisciplinary" is not a buzzword, but a way of life.’ —J. Kelly Nestruck, Globe and Mail ‘Jordan is one of the most talented and exciting playwrights in the country, and he will be a force to be reckoned with for years to come.’ —Nicolas Billon, Governor General's Award–winning playwright (Fault Lines)

This volume compiles ideas and projects from well-known artists, architects, designers, filmmakers and researchers on mountainous regions not only in Switzerland, but worldwide. It includes writings by Vito Acconci, Doug Aitken, Ron Arad, Nairy Baghramian and Jan von Brevern, as well as a discussion on architect Bruno Taut's "Crystal Chain Letters."

Not all charms fly at the touch of cold philosophy. Vital Reenchantments examines so-called cold philosophy, or science, that does precisely the opposite - rather than mercilessly emptying out and unweaving, it operates as a philosophy that animates. More specifically, Greyson closely examines how a specific group of "poet-in-scientists" of the late 1970s and 1980s directed attention to the "wondrous" unfolding of life, at a time when the counter-culture in particular had made the institution of science synonymous with technologies of alienation and destruction. In this vein, Vital Reenchantments takes up E.O. Wilson's Biophilia (1984), James Lovelock's Gaia (1979), and Carl Sagan's Cosmos (1980), in order to show how each work fleshes out scientific concepts with a unique attention to "affective wonder," understood as the experience of and attunement to novel effects. What is so unique about these works is that they reenchant the scientific world without pandering to what Richard Dawkins will later term "cosmic sentimentality." Carl Sagan may have said "We are made of starstuff," but he would never insist, as Joni Mitchell did in 1969, that "we've got to get ourselves back to the garden." Instead, they insist on a third way that does not rely on the idea of an ecological Eden - a vigorously vital materialism in which the affective trumps the sentimental. Further, the historical emergence of these works, all published within 5 years of each other, was no accident: each book responded to an ever deepening sense of environmental crisis, certainly, but along with it they responded to, perhaps more than marginally related, narratives of the large-scale disenchantment brought on by modernity or science, and more often than not a mixture of the two. Greyson argues that the persistence of these works and their affectively-charged scientific concepts in contemporary popular culture and ecological thought is no accident. As such, these works deserve recognition as far more than "popular science" and can be seen as essential contributions to more contemporary vital materialist thought and ecological theory. No doubt this talk of enchantment and wonder, so tied to immediate experience, can seem trivial in the face of any number of environmental crises (global warming first among these) that do not just appear ominously on the horizon, but loom as never before. The first task of this book thus to pose the same question that Jane Bennett does at the end of her own work on enchantment: "How can someone write a book about enchantment in such a world?" Does this approach really provide, as Latour phrases it, "a way to bridge the distance between the scale of the phenomena we hear about and the tiny Umwelt inside which we witness, as if it were a fish inside its bowl, an ocean of catastrophes that are supposed to unfold"? Ultimately, Vital Reenchantments argues that affective ecologies, properly attended to, point toward an open present, one that broadens the horizons of the "fish bowl" and allows us to imagine engendering futures that are neither naively hopeful nor hopelessly apocalyptic.

A game-changing book on the origins of life, called the most important scientific discovery 'since the Copernican revolution' in The Observer.

An ethnographic exploration of technoscientific immortality Immortality has long been considered the domain of religion. But immortality projects have gained increasing legitimacy and power in the world of science and technology. With recent rapid advances in biology, nanotechnology, and artificial intelligence, secular immortalists hope for and work toward a future without death. On Not Dying is an anthropological, historical, and philosophical exploration of immortality as a secular and scientific category. Based on an ethnography of immortalist communities—those who believe humans can extend their personal existence indefinitely through technological means—and an examination of other institutions involved at the end of life, Abou Farman argues that secular immortalism is an important site to explore the tensions inherent in secularism: how to accept death but extend life; knowing the future is open but your future is finite; that life has meaning but the universe is meaningless. As secularism denies a soul, an afterlife, and a cosmic purpose, conflicts arise around the relationship of mind and body, individual finitude and the infinity of time and the cosmos, and the purpose of life. Immortalism today, Farman argues, is shaped by these historical and culturally situated tensions. Immortalist projects go beyond extending life, confronting dualism and cosmic alienation by imagining (and producing) informatic selves separate from the biological body but connected to a cosmic unfolding. On Not Dying interrogates the social implications of technoscientific immortalism and raises important political questions. Whose life will be extended? Will these technologies be available to all, or will they reproduce racial and geopolitical hierarchies? As human life on earth is threatened in the Anthropocene, why should life be extended, and what will that prolonged existence look like?

*** Granta Best of Young American Novelists 2017 *** In a snow-covered village in Chechnya, eight-year-old Havaa watches from the woods as her father is abducted in the middle of the night by Russian soldiers. Their life-long friend and neighbour, Akhmed, has also been watching, and when he finds Havaa he knows of only one person who might be able to help. For tough-minded doctor Sonja Rabina, it’s just another day of trying to keep her bombed-out, abandoned hospital going. When Akhmed arrives with Havaa, asking Sonja for shelter, she has no idea who the pair are. But over the course of five extraordinary days, Sonja’s world will shift on its axis, revealing the intricate pattern of connections that binds these three unlikely companions together and unexpectedly decides their fate. 'A Constellation of Vital Phenomena is simply spectacular' Ann Patchett

Charlotte Mason looked at the world and saw that it was governed by universal laws, such as the law of gravity. Then she wondered. What if there were similar laws that governed the way people learn? If we knew what those laws were, we'd be able to pursue education along the most promising lines . She devoted her life to finding the key principles of education and then developing methods to make the most of them. The result is a comprehensive picture of living and learning that breathes life into education at every level--from babyhood to the adult years. It's not a rote system, but a flexible set of ideas that keep education in focus. These principles are for everyone concerned with teaching and learning. They are no more difficult to implement than the principle of gravity which allows you to walk, run, and even--when you know what you are doing--to soar.

The Vital Center is an eloquent and incisive defense of liberal democracy against its rivals to the left and to the right, communism and fascism. Originally published in 1949, it shows how the failures of free society led to the disenchantment of the masses with democracy, and sharpened the appeal of totalitarian solutions. The book calls for a radical reconstruction of the democratic polity based on a realistic understanding of human limitations and frailties.

WINNER OF THE PEN/HEMINGWAY AWARD FOR DEBUT FICTION SHORTLISTED FOR THE VCU/CABELL FIRST NOVELIST AWARD AND LONGLISTED FOR THE CENTER FOR FICTION FIRST NOVEL PRIZE “[A] scorching desert-noir. . . . Like her nervy protagonists, Tomar is a taker of risks.” —New York Times Book Review “Breathtaking . . . For Penny and Cale, violence looms at all corners and in Tomar’s compassionate rendering, they are imbued with strength, fortitude and fierceness.” —San Francisco Chronicle Cale Lambert, a bookish loner of mysterious parentage, lives in a dusty town near the California-Nevada border, a place where coyotes scavenge for backyard dogs and long-haul truckers scavenge for pills and girls. Cale was raised by her grandfather in a loving, if codependent, household, but as soon as she's left high school his health begins an agonizing decline. Set adrift for the first time, Cale starts waitressing at the local diner, where she reconnects with Penélope Reyes, a charismatic former classmate running mysterious side-hustles to fund her dreams. Penny exposes Cale to the reality that exists beyond their small town, and the girls become inseparable—until one terrifying act of violence shatters their world. When Penny vanishes without a trace, Cale must set off on a dangerous quest across the desert to find her friend, and discover herself. An audacious debut, told in deftly interwoven chapters, A Prayer for Travelers explores the complicated legacy of the American West and the trauma of female experience.