Although the genetic code is defined by a linear array of nucleotides, it is the three‐dimensional structure of the double helix that regulates most of its cellular functions. Over the past two decades, it has become increasingly clear that aspects of this three‐dimensionality which reflect topological relationships within the double helix (i.e., superhelical twisting, knotting, or tangling) influence virtually every facet of nucleic acid physiology. In vivo, DNA topology is modulated by ubiquitous enzymes known as topoisomerases. The type II enzyme (...) essential to the eukaryotic cell and is required for unlinking daughter chromosomes and maintaining chromosome structure. Moreover, topoisomerase II also has been identified as the primary cellular target for several widely used antineoplastic drugs. Before the physiological functions of topoisomerase II can be effectively dissected or its drug interactions fully exploited, it is imperative to understand the mechanism by which this important enzyme arries out its catalytic cycle. (shrink)

Although the genetic code is defined by a linear array of nucleotides, it is the three‐dimensional structure of the double helix that regulates most of its cellular functions. Over the past two decades, it has become increasingly clear that aspects of this three‐dimensionality which reflect topological relationships within the double helix (i.e., superhelical twisting, knotting, or tangling) influence virtually every facet of nucleic acid physiology. In vivo, DNA topology is modulated by ubiquitous enzymes known as topoisomerases. The type II enzyme (...) essential to the eukaryotic cell and is required for unlinking daughter chromosomes and maintaining chromosome structure. Moreover, topoisomerase II also has been identified as the primary cellular target for several widely used antineoplastic drugs. Before the physiological functions of topoisomerase II can be effectively dissected or its drug interactions fully exploited, it is imperative to understand the mechanism by which this important enzyme arries out its catalytic cycle. (shrink)

A general framework by which dynamic interactions within a protein will promote the necessary series of structural changes, or “conformational cycle,” required for function is proposed. It is suggested that the free‐energy landscape of a protein is biased toward this conformational cycle. Fluctuations into higher energy, although thermally accessible, conformations drive the conformational cycle forward. The amino acid interaction network is defined as those intraprotein interactions that contribute most to the free‐energy landscape. Some network connections are consistent (...) in every structural state, while others periodically change their interaction strength according to the conformational cycle. It is reviewed here that structural transitions change these periodic network connections, which then predisposes the protein toward the next set of network changes, and hence the next structural change. These concepts are illustrated by recent work on tryptophan synthase. Disruption of these dynamic connections may lead to aberrant protein function and disease states. (shrink)

Myosin self‐assembly is generally considered to be the major process in thick filament formation within striated muscles. The biological assembly of myosin into thick filaments is being analysed by genetic dissection as well as biochemical and morphological experiments in the nematode Caenorhabditis elegans. This work shows that the assembly of myosin is modulated by its biosynthesis and interaction with non‐myosin proteins. Assemblages which generate multiple nascent thick filaments may play a central role in a catalytic cycle of myosin (...) assembly. (shrink)

The RecA family proteins mediate homologous recombination, a ubiquitous mechanism for repairing DNA double‐strand breaks (DSBs) and stalled replication forks. Members of this family include bacterial RecA, archaeal RadA and Rad51, and eukaryotic Rad51 and Dmc1. These proteins bind to single‐stranded DNA at a DSB site to form a presynaptic nucleoprotein filament, align this presynaptic filament with homologous sequences in another double‐stranded DNA segment, promote DNA strand exchange and then dissociate. It was generally accepted that RecA family proteins function throughout (...) their catalytic cycles as right‐handed helical filaments with six protomers per helical turn. However, we recently reported that archaeal RadA proteins can also form an extended right‐handed filament with three monomers per helical turn and a left‐handed protein filament with four monomers per helical turn. Subsequent structural and functional analyses suggest that RecA family protein filaments, similar to the F1‐ATPase rotary motor, perform ATP‐dependent clockwise axial rotation during their catalytic cycles. This new hypothesis has opened a new avenue for understanding the molecular mechanism of RecA family proteins in homologous recombination. BioEssays 30:48–56, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

The RecA family proteins mediate homologous recombination, a ubiquitous mechanism for repairing DNA double‐strand breaks (DSBs) and stalled replication forks. Members of this family include bacterial RecA, archaeal RadA and Rad51, and eukaryotic Rad51 and Dmc1. These proteins bind to single‐stranded DNA at a DSB site to form a presynaptic nucleoprotein filament, align this presynaptic filament with homologous sequences in another double‐stranded DNA segment, promote DNA strand exchange and then dissociate. It was generally accepted that RecA family proteins function throughout (...) their catalytic cycles as right‐handed helical filaments with six protomers per helical turn. However, we recently reported that archaeal RadA proteins can also form an extended right‐handed filament with three monomers per helical turn and a left‐handed protein filament with four monomers per helical turn. Subsequent structural and functional analyses suggest that RecA family protein filaments, similar to the F1‐ATPase rotary motor, perform ATP‐dependent clockwise axial rotation during their catalytic cycles. This new hypothesis has opened a new avenue for understanding the molecular mechanism of RecA family proteins in homologous recombination. BioEssays 30:48–56, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

Deciphering how DCAFs (DDB1‐CUL4 Associated Factors) modulate a broad spectrum of cellular processes, including cell cycle progression and maintenance of genomic integrity is critical to better understand cellular homeostasis and diseases. Cells contain more than 100 DCAFs that associate with the Cullin‐Ring Ubiquitin Ligase 4 (CRL4) complex that target specific protein substrates for degradation. DCAFs are thought to act as substrate receptors that dictate the specificity of the ubiquitination machinery (“catalytic DCAFs”). However, recent studies have suggested that some (...) DCAFs might play a different role by targeting CRL4 complexes to distinct cellular compartments (“structural DCAFs”). Once localized to their correct cellular domains, these CRLs dissociate from the structural DCAFs prior to their association with other, substrate‐specific catalytic DCAFs. Thus, we propose that DCAF switches can provide a mechanistic basis for the degradation of proteins that regulate cell growth and proliferation at precise points in space and time. (shrink)

Origin of a dissipative structure in a chemical dynamic system: occurs under the following constraints: 1) Affinity must be high. (The system must be far from equilibrium.); 2) There must be an auto-catalytic process; 3) A process that reduces the concentration of the auto-catalyst must operate; 4) The relevant parameters (rate constants, etc.) must lie in a range corresponding to a limit cycle trajectory. That is, there must be closure of the network of reaction such that a state (...) sufficiently close to the prior condition is achieved at the corresponding part of each oscillation. If these constraints continue to be met interactions of the system with the rest of the world are quite different in the presence of the dissipative structure than they would be in the absence of that self-organized coherence. Closure of a network of relationships which gives rise to a dissipative structure is a 'unit-determining' feature. The effects of the structure as a whole are the resultants of the effects of the components, but the concentrations of the components at any instant are effects of the closure of the limit cycle. This is an influence on components arising from what those components constitute --- downward causation. (shrink)

A simple molecular system is described consisting of the reciprocal linkage between an autocatalytic cycle and a self-assembling encapsulation process where the molecular constituents for the capsule are products of the autocatalysis. In a molecular environment sufficiently rich in the substrates, capsule growth will also occur with high predictability. Growth to closure will be most probable in the vicinity of the most prolific autocatalysis and will thus tend to spontaneously enclose supportive catalysts within the capsule interior. If subsequently disrupted (...) in the presence of new substrates, the released components will initiate production of additional catalytic and capsule components that will spontaneously re-assemble into one or more autocell replicas, thereby reconstituting and sometimes reproducing the original. In a diverse molecular environment, cycles of disruption and enclosure will cause auto-cells to incidentally encapsulate other molecules as well as reactive substrates. To the extent that any captured molecule can be incorporated into the autocatalytic process by virtue of structural degeneracy of the catalytic binding sites, the altered autocell will incorporate the new type of component into subsequent replications. Such altered autocells will be progenitors of “lineages” with variant characteristics that will differentially propagate with respect to the availability of commonly required substrates. Autocells are susceptible to a limited form of evolution, capable of leading to more efficient, more environmentally fitted, and more complex forms. This provides a simple demonstration of the plausibility of open-ended reproduction and evolvability without self-replicating template molecules or maintenance of persistent nonequilibrium chemistry. This model identifies an intermediate domain between prebiotic and biotic systems and bridges the gap from nonequilibrium thermodynamics to life. (shrink)

The process of condensation of an amorphous solid into a rigid matrix can often trap molecules in reversible binding sites. Exchange of the same molecular species with such sites is known to be sensitive to small chemical differences and to distinguish between enantiomers. In addition to their usefulness in chromatographic processes, such materials can separate, by solid phase extraction, specific compounds from complex mixtures. Furthermore, the trapped molecules can have their reactions guided and catalytically changed. The combination of this spontaneously (...) formed system of templates and catalytic sites may support a type of replication cycle, and suggests some pathways from simple chemistry toward the complexities of biology. © 2005 Wiley Periodicals, Inc. Complexity 11: 30–35, 2005 -/- . (shrink)

Rho, a member of the Ras superfamily of small GTPases, has multiple biological roles: it regulates signal trasduction pathways linking extracellular growth factors to the assembly of actin stress fibres and focal adhesion complexes; it is required for G1 progression and activates the SRF transcription factor when quiescent fibroblasts are stimulated to grow; and it plays a role later in the cell cycle during cytokinesis. Two groups have recently succeeded in identifying downstream effectors of Rho that may mediate some (...) of these biological effects. One protein identified by both groups is protein kinase N (PKN), a serine/threonine kinase whose catalytic domain is closely related to that of protein kinase C(1,2). (shrink)

The immunoglobulin molecule is a perfect template for the de novo generation of biocatalytic functions. Catalytic antibodies, or abzymes, obtained by the structural mimicking of enzyme active sites have been shown to catalyze numerous chemical reactions. Natural enzyme analogs for some of these reactions have not yet been found or possibly do not exist at all. Nowadays, the dramatic breakthrough in antibody engineering and expression technologies has promoted a considerable expansion of immunoglobulin's medical applications and is offering abzymes a (...) unique chance to become a promising source of high‐precision “catalytic vaccines.” At the same time, the discovery of natural abzymes on the background of autoimmune disease revealed their beneficial and pathogenic roles in the disease progression. Thus, the conflicting Dr. Jekyll and Mr. Hyde protective and destructive essences of catalytic antibodies should be carefully considered in the development of therapeutic abzyme applications. (shrink)

The nature/nurture debate is not dead. Dichotomous views of development still underlie many fundamental debates in the biological and social sciences. Developmental systems theory offers a new conceptual framework with which to resolve such debates. DST views ontogeny as contingent cycles of interaction among a varied set of developmental resources, no one of which controls the process. These factors include DNA, cellular and organismic structure, and social and ecological interactions. DST has excited interest from a wide range of researchers, from (...) molecular biologists to anthropologists, because of its ability to integrate evolutionary theory and other disciplines without falling into traditional oppositions. The book provides historical background to DST, recent theoretical findings on the mechanisms of heredity, applications of the DST framework to behavioral development, implications of DST for the philosophy of biology, and critical reactions to DST. (shrink)

The article aims to define the management mechanism of complex, open dynamic systems with human participation. The following parts of the system life-cycle were identified and unified in the theoretical scope: general and specific compositional elements of repeating changes, marginal index boundaries, the dynamics of the compositional elements of the lifecycle, the key points of the change in the character of the index dynamics. In the practical scope, two common trends of socio-economical system life-cycle management are considered. The (...) first trend is the regulation of the comprising element ratio, which provides the increase in the duration of the maximally effective performance of a functioning system. The second trend is the regulation of the reproduction time of a new system. The systems life cycle aspects are investigated in almost all sciences and studied within many disciplines in the field of higher education. Therefore, deepening the mastery of scientific and methodological foundations of the life cycle of a complex open dynamic system is useful for any subject in everyday and practical activities. A human being – in the formation of own human capital. Families – when it is formed, the birth of children, the distribution of income and expenses. Companies – for efficient business activities. As well as local communities, local self-government bodies, public authorities and global entities within their profile activities. The results of the research provide the possibility of the development of applicable mechanisms for effectiveness and stability enhancement of managerial and entrepreneurial operation in business projects. (shrink)

This chapter contains sections titled: Child's Play Adolescent Infatuation Flourishing Adulthood Midlife Crisis Pit Stop Unreflective Maturity Maturity Cycles to Sofia (No, Not the Bulgarian Capital) Old Age Re‐Cycling Notes.

This study shows that double thymidine block treatment efficiently arrests the EO771 cells in the S‐phase without altering cell growth or survival. A long‐term analysis of cell behavior, using 5(6)‐carboxyfluorescein diacetate N‐succinimidyl ester (CFSE) staining, show synchronization to be stable and consistent over time. The EO771 cell line is a medullary breast‐adenocarcinoma cell line isolated from a spontaneous murine mammary tumor, and can be used to generate murine tumor implantation models. Different biological (serum or amino acid deprivation), physical (elutriation, mitotic (...) shake‐off), or chemical (colchicine, nocodazole, thymidine) treatments are widely used for cell synchronization. Of the different methods tested, the double thymidine block is the most efficient for synchronization of murine EO771 cells if a large quantity of highly synchronized cells is recommended to study functional and biochemical events occurring in specific points of cell cycle progression. (shrink)

Cet ouvrage de référence est une vaste synthèse qui présente la doctrine traditionnelle des cycles développée et appliquée à notre temps. La cyclologie, ou théorie du temps cyclique, est une conception que l'on retrouve dans la plupart des sociétés archaïques. Selon cette vision, l'écoulement du temps n'est pas linéaire, l'histoire passant pour obéir éternellement à des cycles immuables amenant un retour périodique de l'humanité face aux mêmes situations, cycles dont la durée varie selon les traditions. La plus répandue et la (...) plus ancienne des conceptions cycliques est la mesure védique du temps en quatre âges, encore développée aujourd'hui dans l'hindouisme et le bouddhisme. Le cycle complet dure 12 000 ans environ et débute par un Age d'Or, période où l'homme possède la connaissance spirituelle et vit dans une harmonie parfaite. Puis continence le déclin (perte progressive de la connaissance) qui, en passant par l'Age d'Argent puis l'Age de Bronze, aboutit à l'Age de Fer (Kali Youga) où triomphent l'ignorance, l'égoïsme et le mal. Une conflagration (sous la forme d'un cataclysme cosmique, de guerres ou autre) purifie ensuite l'humanité pour permettre le commencement d'un nouveau cycle, donc d'un nouvel Age d'Or. Bien qu'elle soit en contradiction avec les doctrines judéo-chrétiennes qui véhiculent une vision linéaire du temps, de la Création et de la fin du inonde, la cyclologie s'est perpétuée jusqu'à nos jours, véhiculée par divers courants philosophiques. A l'aide de cette théorie, Jean Phaure a la vertu de nous faire comprendre que ce que nous vivons et la fin de cycle qui nous attend n'arrivent pas pour la première fois et ont déjà eu lieu avec des intensités différentes ; c'est un perpétuel recommencement. (shrink)

We invite systematic consideration of the metaphors of cycles and circulation as a long-term theme in the history of the life and environmental sciences and medicine. Ubiquitous in ancient religious and philosophical traditions, especially in representing the seasons and the motions of celestial bodies, circles once symbolized perfection. Over the centuries cyclic images in western medicine, natural philosophy, natural history and eventually biology gained independence from cosmology and theology and came to depend less on strictly circular forms. As potent ‘canonical (...) icons’, cycles also interacted with representations of linear and irreversible change, including arrows, arcs, scales, series and trees, as in theories of the Earth and of evolution. In modern times life cycles and reproductive cycles have often been held to characterize life, in some cases especially female life, while human efforts selectively to foster and disrupt these cycles have harnessed their productivity in medicine and agriculture. But strong cyclic metaphors have continued to link physiology and climatology, medicine and economics, and biology and manufacturing, notably through the relations between land, food and population. From the grand nineteenth-century transformations of matter to systems ecology, the circulation of molecules through organic and inorganic compartments has posed the problem of maintaining identity in the face of flux and highlights the seductive ability of cyclic schemes to imply closure where no original state was in fact restored. More concerted attention to cycles and circulation will enrich analyses of the power of metaphors to naturalize understandings of life and their shaping by practical interests and political imaginations. (shrink)

Focal adhesions disassemble during mitosis, but surprisingly little is known about how these structures respond to other phases of the cell cycle. Three recent papers reveal unexpected results as they examine adhesions through the cell cycle. A biphasic response is detected where focal adhesions grow during S phase before disassembly begins early in G2. In M phase, activated integrins at the tips of retraction fibers anchor mitotic cells, but these adhesions lack the defining components of focal adhesions, such (...) as talin, paxillin, and zyxin. Re‐examining cell‐matrix adhesion reveals reticular adhesions, a new class of adhesion. These αVβ5 integrin‐mediated adhesions also lack conventional focal adhesion components and anchor mitotic cells to the extracellular matrix. As reviewed here, these studies present insight into how adhesion complexes vary through the cell cycle, and how unconventional adhesions maintain attachment during mitosis while providing spatial memory to guide daughter cell re‐spreading after cell division. (shrink)

All parts of Heraclitus’ cosmos are simultaneously living and dying. Its constituent stuffs (“biomasses”) cycle endlessly through physical changes in sweeping patterns (“biorhythms”) that are reflected in the dynamic rhythms of Heraclitus’ own thought and language. These natural processes are best examined at a more-than-human level that exceeds individuation, stable identity, rational comprehension, and linguistic capture. B62 (“mortals immortals”), one of Heraclitus’ most perplexing fragments, models these processes in a spectacular fashion: it describes the imbrication not only of humans (...) and gods but of cosmic masses more generally, and its language mimics the natural relations that it names, or rather intimates through its grammatical and syntactical indeterminacy. The remaining fragments amplify the uncertainties and the exhilarations of Heraclitus’ worldview along the same lines. His approach to nature raises urgent questions about how human beings fit into the cosmos, not least by challenging our intuitive conceptions of life and death, our material makeup, and our entanglements with our natural surroundings. In doing so, he provides vital lessons for contemporary ecological awareness, and proves to be an unexpected ally. (shrink)

Cet article s’inscrit dans la lignée de précédents travaux visant à rapprocher l’entrepreneur schumpétérien et le surhumain nietzschéen. Les deux partagent une créativité pouvant s’interpréter comme l’extériorisation d’un surcroît de force qui, dans l’optique nietzschéenne, s’assimile à la source extra-morale de l’accroissement de la vie. Reste à savoir si le cadre dans lequel ils évoluent est le même. Au-delà d’une approche historique du cycle de la conjoncture, notre hypothèse est que l’approche philosophique d’un cycle du devenir s’avère être (...) féconde pour une interprétation enrichie du cycle de la conjoncture, complétant et prolongeant ainsi notre interprétation du surhumain et de l’entrepreneur. (shrink)

Business cycle theory is a broad and disparate field. Different schools of thought offer alternative explanations for cycles, often using different mathematical methods. This book provides academics and graduate students of economics with a compact and accessible exposition of business cycle theory since Keynes. The author places the main theories -- Keynesian economics, monetarism, new classical economics, the real business cycles theory, and new Keynesian economics -- in an historical context by presenting them in the chronological order of (...) their appearance and highlighting their differences and commonalities. He minimizes the necessary mathematical prerequisites by using a unifying mathematical approach: stochastic second-order difference equations, which is explained in detail. Throughout the book, the international dimension of business cycles is acknowledged. The theoretical results obtained are set alongside empirical facts in separate boxes. Each chapter finishes with a set of problems designed to deepen the reader's understanding of the theories presented, and further reading sections which provide access to related material. (shrink)

We propose a Condorcet-consistent voting method that we call Split Cycle. Split Cycle belongs to the small family of known voting methods satisfying the anti-vote-splitting criterion of independence of clones. In this family, only Split Cycle satisfies a new criterion we call immunity to spoilers, which concerns adding candidates to elections, as well as the known criteria of positive involvement and negative involvement, which concern adding voters to elections. Thus, in contrast to other clone-independent methods, Split (...) class='Hi'>Cycle mitigates both “spoiler effects” and “strong no show paradoxes.”. (shrink)

It is a long-standing view that global translation varies during the cell cycle and is much lower in mitosis than in other cell-cycle phases. However, the central papers in the literature are not in agreement about the extent of downregulation in mitosis, ranging from a dramatic decrease to only a marginal reduction. Herein, it is argued that the discrepancy derives from technical challenges. Cell-cycle-dependent variations are most conveniently studied in synchronized cells, but the synchronization methods by themselves (...) often evoke stress responses that, in turn, affect translation rates. Further, it is argued that previously reported cell-cycle-dependent changes in the global translation rate to a large extent reflect responses to the synchronization methods. Recent findings strongly suggest that the global translation rate is not regulated in a cell-cycle-dependent manner. Novel techniques allowing a genome-wide analysis of translational profiles suggest that the extent and importance of selective translational regulation associated with cell-cycle transitions have been underestimated. Therefore, the main question is which messenger RNAs (mRNAs) are translated, rather than whether the global translation rate is decreased. (shrink)

Cycles of Personal Belief by Waldo Emerson Forbes.

Hormonal changes associated with the human menstrual cycle have been previously found to affect female mate preference, whereby women in the late follicular phase of their cycle (i.e., at higher risk of conception) prefer males displaying putative signals of underlying genetic fitness. Past research also suggests that romantic kissing is utilized in human mating contexts to assess potential mating partners. The current study examined whether women in their late follicular cycle phase place greater value on kissing at (...) times when it might help serve mate assessment functions. Using an international online questionnaire, results showed that women in the follicular phase of their menstrual cycle felt that kissing was more important at initial stages of a relationship than women in the luteal phase of their cycle. Furthermore, it was found that estimated progesterone levels were a significant negative predictor for these ratings. (shrink)

By means of the averaging method of the first order, we introduce the maximum number of limit cycles which can be bifurcated from the periodic orbits of a Hamiltonian system. Besides, the perturbation has been used for a particular class of the polynomial differential systems.

The article analyzes the dependence of the phenomenon of education on the type of civilization in space of which the life of the world community takes place. It is based on the interaction of social institutions of the market, science and education. It “proceeds” on the surface by the division of social labor, which generates a specific form of social system of education in dependence on the social division of labor in specific socio-economic conditions. To reproduce effectively its structural and (...) functional parameters, the author suggests resorting to the paradigm of the «life cycle of educational systems in the context of a civilizational approach» based on the use of cognitive analysis. Its advantage is only that the concept «grasps» the phenomenon of education as a whole. This means that the phenomenon of civilization education is studied as a social institution and social system of the industrial society. To analyze the dynamics of knowledge change, two methodological conditions must be used: to apply the civilizational approach and the paradigm of the life cycle of social systems, since this phenomenon has a long-lasting dimension in space and time; the meaning of educational content at each stage of industrial civilization life is distinguished: natural knowledge prevailed at the stage of its origin; at the stage of growth - technical knowledge that corresponded to the essence of civilization itself; at the stage of maturity - scientific knowledge turned into ideologues of social development, which led to the emergence of technocratism and “drove” the planetary community into a dead end; at the stage of decline - technological knowledge led to the loss of mainstream guide of social development and began the catastrophic destruction of the social organism of the planet, which entails a change in the type of civilizational development; the solution is seen in the rise of the planetary community into the space of informational civilization, the transition of education to mastering methodological knowledge corresponds to it. (shrink)

Forty years of avid bicycling came to a conclusion for D. Stephen Long in early October, 2020. Fearing his own imminent death required Long to reflect on life, on its beginnings, middle, and endings. This work uses the lessons learned from cycling, and the experience of the rapid onset of illness, to discuss God, friendship, racism, sexuality, justice, virtues, vices, and much more. It offers a moral theology but one more in keeping with how we take it up--not through theories (...) but in the practices that make up everyday life. Attention to everyday life can help us live well and in so doing prepare us to die well. " -- Publisher description. (shrink)

It has become a standard for researchers carrying out biotechnology projects to do a life cycle assessment. This is a process for assessing the environmental impact of a technology, product or policy. Doing so is no simple matter, and in the last decades, a rich set of methodologies has developed around LCA. However, the proper methods and meanings of the process remain contested. Preceding the development of the international standard that now governs LCA, there was a lively debate in (...) the academic community about the inclusion of ‘values’ within the process. We revisit this debate and reconsider the way forward for LCA. We set out ways in which those outside of science can provide input into LCAs by informing the value assumptions at stake. At the same time, we will emphasize that the role of those within the scientific community need not involve value-free inquiry. We carry out this exploration through a case study of a particular technology project that sought ways to produce industrial and consumer products from algal oils. (shrink)

Covering interesting and varied philosophical terrain, _Cycling - Philosophy for Everyone_ explores in a fun but critical way the rich philosophical, cultural, and existential experiences that arise when two wheels are propelled by human energy. Incorporates or reflects the views of high-profile and notable past-professional cyclists and insiders such as Lennard Zinn, Scott Tinley, and Lance Armstrong Features contributions from the areas of cultural studies, kinesiology, literature, and political science as well as from philosophers Includes enlightening essays on the varieties (...) of the cycling experience, ranging from the ethical issues of success, women and cycling, environmental issues of commuting and the transformative potential of cycling for personal growth Shows how bicycling and philosophy create the perfect tandem Includes a foreword by Lennard Zinn, author and owner of Zinn Cycles Inc. (shrink)

Recent high-profile corporate scandals are reminiscent of the corporate raider scandals of the 1980s, suggesting that ethical scandals may occur in waves. This article provides a framework for analysis of this question by suggesting that ethical attitudes may be cyclical about long-term secular trends. We provide some empirical evidence from previously published work for the existence of cycles as well as a potential mechanism for their propagation, namely widespread publicity about a particularly salient event, e.g., Enron. Further, we posit that (...) long-run secular trends would be affected through more deliberate, cognitive means, e.g., instruction in business ethics. We also discuss an important research implication, namely that traditional cross-sectional “book-end” studies surveying ethical attitudes at two different points in time may be unable to disentangle short-run cyclical movements from long-term secular trends. (shrink)

Mixed-strategy equilibria are typically rather unstable in evolutionary game theory. “Monocyclic” games, such as Rock–Paper–Scissors, have only mixed equilibria, some of which are “stable” in the sense that sequential best replies lead to them; yet, even these games are prone to stable cycles under discrete-time simultaneous best replies, giving an unusual equilibrium-selection problem. This article analyzes such games in a random-utility setting where changing strategies is costly, and the speed of the dynamic is, thus, endogenous. The stochastically stable outcome is (...) determined by the cost of switching strategies; when switching costs are high, mixed equilibria are selected, whereas when switching costs are low, cycles are selected. (shrink)

Providing equitable food security for a growing population while minimizing environmental impacts and enhancing resilience to climate shocks is an ongoing challenge. Here, we quantify the resource intensity, environmental impacts and nutritional output of a small (0.075 ha) low-input subsistence Mediterranean agroecological farm in a developed nation that is based on intercropping and annual crop rotation. The farm provides one individual, the proprietor, with nutritional self-sufficiency (adequate intake of an array of macro- and micro-nutrients) with limited labor, no synthetic fertilizers (...) or herbicides, and zero waste, effectively closing a full farm-table-farm cycle. We find that the agroecological farm outperforms conventional farming as practiced in the same country in terms of both lower environmental burdens, across all examined environmental metrics (63% lower on average) per kg produce, and higher nutritional score (66% higher on average). Per equal farmland, the environmental lopsidedness was even higher (79% lower than conventional farming on average), with nearly the same nutritional score (3% lower on average). Moreover, when considering total land area, which includes farmland and supporting non-agricultural lands, as well as postgate impacts and food losses, the advantage of the agroecological system over conventional farming is even more pronounced. Situated within a Mediterranean region that is undergoing rapid climate change, this food system is a unique case study of nutrition- and environment-oriented food production system. While its deployment potential is limited by lack of supportive policies, it nonetheless represents one of the most starkly bold alternatives to current food systems. (shrink)

A range of extremely plausible moral principles turn out to generate “deontic cycling”: sets of actions wherein I have stronger reason to do B than A, C than B, and A than C. Indeed, just about anything recognizable as commonsense morality generates deontic cycling. This matters for two reasons. First, it creates a problem for the widely held view that agent-centered rankings can square consequentialism with commonsense morality. Second, it forces a choice between some deeply plausible views about rationality—wherein someone (...) cannot have stronger reason to do A than B, B than C, and C than A—and commonsense morality. (shrink)

Historians of science have attributed the emergence of ecology as a discipline in the late nineteenth century to the synthesis of Humboldtian botanical geography and Darwinian evolution. In this essay, I begin to explore another, largely neglected but very important dimension of this history. Using Sergei Vinogradskii’s career and scientific research trajectory as a point of entry, I illustrate the manner in which microbiologists, chemists, botanists, and plant physiologists inscribed the concept of a “cycle of life” into their investigations. (...) Their research transformed a longstanding notion into the fundamental approaches and concepts that underlay the new ecological disciplines that emerged in the 1920s. Pasteur thus joins Humboldt as a foundational figure in ecological thinking, and the broader picture that emerges of the history of ecology explains some otherwise puzzling features of that discipline – such as its fusion of experimental and natural historical methodologies. Vinogradskii’s personal “cycle of life” is also interesting as an example of the interplay between Russian and Western European scientific networks and intellectual traditions. Trained in Russia to investigate nature as a super-organism comprised of circulating energy, matter, and life; over the course of five decades – in contact with scientists and scientific discourses in France, Germany, and Switzerland – he developed a series of research methods that translated the concept of a “cycle of life” into an ecologically conceived soil science and microbiology in the 1920s and 1930s. These methods, bolstered by his authority as a founding father of microbiology, captured the attention of an international network of scientists. Vinogradskii’s conceptualization of the “cycle of life” as chemosynthesis, autotrophy, and global nutrient cycles attracted the attention of ecosystem ecologists; and his methods appealed to practitioners at agricultural experiment stations and microbiological institutes in the United States, Western Europe, and the Soviet Union. (shrink)

In the years following its publication, F.A. Hayek's pioneering work on business cycles was regarded as an important challenge to what was later known as Keynesian macroeconomics. Today, economists are once again paying heed to Hayek's thoughts. This volume bring together his work on what causes periods of boom and bust in the economy.

Across the world, the lives of men and women who are otherwise similarly situated tend to differ from each other systematically. Although gender disparities varywidely within and among regions, women everywhere are disproportionately vulnerable to poverty, abuse and political marginalization. This article proposes thatglobal gender disparities are caused by a network of norms, practices, policies, and institutions that include transnational as well as national elements. These interlaced and interacting factors frequently modify and sometimes even reduce gendered vulnerabilities but their overall (...) effect is to maintain and often intensify them. Women’s vulnerabilities in different areas of life mutually reinforce each other and I follow other authors in referring to such causal feedback loops as cycles of gendered vulnerability. I argue that these cycles now operate on a transnational as well as national scale and I illustrate this by discussing the examples of domestic work and sex work. If global institutional arrangements do indeed contribute to maintaining or intensifying distinctively gendered vulnerabilities, these arrangements deserve criti cal scrutiny from philosophers concerned with global justice. (shrink)

Language change can be conceptualized as a cyclical process of continuous renewal of the involved elements which somehow change their nature, with respect to phonological or lexico-grammatical features. A crucial aspect of such diachronic evolution is that cyclical change takes place systematically and follows regular and unidirectional patterns of development. Once the change is complete, the same developmental path will be undertaken by new linguistic items in the same cyclical fashion. In this paper, we illustrate the concept of cyclical change (...) by discussing two examples of linguistic cycles. A first instance of cyclical development is displayed at the phonological level by the diachronic changes in the obstruent consonant system taking place from Indo-European to German through the First and the Second Sound Shift: the cycle is completed in the Cimbrian dialects. A second instance is provided by the diachronic process known as Jespersen’s cycle ([1917] 1966): sentential negation, initially expressed through a single negative marker, is later reinforced by an additional one; eventually, this second element becomes the only negative marker available in the sentence while the original marker is deleted. The discussion of the negative cycle takes also into consideration the results of an empirical research conducted on two varieties of an Italo-Romance dialect spoken in northern Italy. (shrink)

A notorious problem that has recently received increased attention in axiology, normative theory and population ethics is the apparent ubiquity of what can be generally called nondeterminacy. This paper illustrates how nondeterminacy can spawn cyclical rankings. So, accepting that practical reasons can admit of nondeterminacy challenges the widely held idea that ‘better than’ is transitive. As a result, standard approaches to rational choice under nondeterminacy fail to be action-guiding, since in some situations all options are dominated, that is, impermissible according (...) to standard rational choice criteria. (shrink)

Cell cycle arrest in M phase can be induced by the failure of a single chromosome to attach properly to the mitotic spindle. The same cell cycle checkpoint mediates M phase arrest when cells are treated with drugs that either disrupt or hyperstabilize spindle microtubules. Study of yeast mutants that fail to arrest in the presence of microtubule disruptors identified a set of genes important in this checkpoint pathway. Two recent papers report the cloning of human and Xenopus (...) homologues of one of these yeast genes, called MAD2 (for mitotic arrest deficient‐2)(1,2). Introduction of antibodies to the MAD2 protein into living mammalian cells or Xenopus egg extracts abrogates the M phase arrest induced by microtubule inhibitors. This and other recent developments suggest a model for the M phase checkpoint in which unattached kinetochores inhibit the ubiquitination of proteins whose proteolysis is necessary for chromatid separation and exit from mitosis. (shrink)

In this rich cultural history, Pamela Robertson Wojcik examines America's ambivalent and shifting attitude toward homelessness through a close study of film cycles from five distinct historical moments that show characters as unhomed and placeless, mobile rather than fixed: failing, resisting, or opting out of the mandate for a home of one's own. From the tramp films of the Silent Era to the Oscar-winning Nomadland in 2021, Wojcik shows how film cycles reveal a tension in the American imaginary between viewing (...) homelessness as, on the one hand, deviant or threatening, and, on the other, emblematic of freedom and independence. Blending social history with insights drawn from a complex array of films, both canonical and fringe, Wojcik effectively 'unhomes' dominant narratives that cast aspirations for success and social mobility as the focus of American cinema, reminding us that genres of precarity have been central to the American cinema (and American story) all along. (shrink)

Development and maintenance of diverse organ systems require context‐specific regulation of stem cell behaviour. We hypothesize that this is achieved via reciprocal regulation between the cell cycle machinery and differentiation factors. This idea is supported by the parallel evolutionary emergence of differentiation pathways, cell cycle components and complex multicellularity. In addition, the activities of different cell cycle phases have been found to bias cells towards stem cell maintenance or differentiation. Finally, several direct mechanistic links between these two (...) processes have been established. Here, we focus on interactions between cyclin‐CDK complexes and differentiation regulators of the Notch pathway and Sox family of transcription factors within the context of pluripotent and neural stem cells. Thus, this hypothesis formalizes the links between these two processes as an integrated network. Since such factors are common to all stem cells, better understanding their interconnections will help to explain their behaviour in health and disease. (shrink)

This volume is divided into three major parts, each of which symbolizes a new virtuous circle that is added to the previous one in order to foster the dissemination of humanistic management among corporations and social institutions. After an introductory chapter explaining the concept of humanistic management and the plan behind this research project, the first part of the book is devoted to education. The authors address pedagogical strategies that can be used in higher education to introduce students to HM. (...) In turn, the second part of the book focuses on the implementation of HM in corporations, while the third presents an approach for measuring and monetizing the social value generated by corporations through their economic activities. In the closing chapter, the editors illustrate how the three parts of the book can be combined to generate virtuous cycles in corporations. (shrink)

In nature, cells face a variety of stresses that cause physical damage to the plasma membrane and cell wall. It is well established that evolutionarily conserved cell cycle checkpoints monitor various cellular perturbations, including DNA damage and spindle misalignment. However, the ability of these cell cycle checkpoints to sense a damaged plasma membrane/cell wall is poorly understood. To the best of our knowledge, our recent paper described the first example of such a checkpoint, using budding yeast as a (...) model. In this review, we will discuss this important question as well as provide hypothetical explanations to be tested in the future. (shrink)

The issue of mandatory cycle helmets is highly contentious. The aim of this paper is not to argue for or against legislation but to suggest criteria on which the debate should focus. This is done by attempting to answer the question: 'What criteria must be met before cycle helmet wearing is enforced?' Consideration is given to principles, precedents and consequences and four criteria are suggested. The criteria are to do with effectiveness, personal liberty, public acceptability and the promotion (...) of the public health benefits of cycling. (shrink)

Real business cycle theory, as exemplified by Fischer Black's Business Cycles and Equilibrium, posits that business cycles are due to random?technology shocks,? and not to monetary, fiscal or other government policies. Rational expectations and complete markets are supposed to enable decision makers to avoid the costly mistakes that would otherwise result from policies that distort incentives to borrow and invest. This paper questions the assumptions of rational expectations and complete markets from an Austrian?school perspective. It argues that decision makers (...) economize on information costs by basing their plans at least in part on the actual prices observed in the course of doing business, and that government regulations have impinged on the evolution of markets, leaving them far from complete. (shrink)