Dependency relationships within the cell cycle allow cells to arrest the cycle reversibly in response to agents or conditions that interfere with specific aspects of its normal progression. In addition, overlapping pathways exist which also arrest the cell cycle in response to DNA damage. Collectively, these control mechanisms have become known as checkpoints. Analysis of checkpoints is facilitated by the fact that dependency relationships within the cell cycle, such as the dependency of mitosis on the completion of DNA synthesis, and (...) the DNA damage checkpoint can be separated genetically. In fission yeast, Schizosaccharomyces pombe, the dependency of mitosis on prior completion of DNA synthesis is mediated through tyrosine‐15 phosphorylation of the ubiquitous mitotic regulator p34cdc2. In contrast, the arrest of mitosis caused by DNA damage acts through a separate mechanism that appears to be independent of tyrosine‐15 phosphorylation. Despite these distinct interactions with the mitotic machinery, the majority of fission yeast mutants that are deficient in mitotic arrest after DNA damage are also unable to respond to inhibition of DNA synthesis. In this essay we survey the current knowledge concerning feedback controls and checkpoints within fission yeast and relate this to information derived from other systems. (shrink)

Has the Internet changed the pattern of social relations? More specifically, have social relations undergone any systematic change during the recent widespread diffusion of new communications technology? This question is addressed using a unique longitudinal survey that bookends the entire period of Internet diffusion in two African nations and one Indian state. We analyze data on nine professional linkages reported by a population of agricultural and environmental scientists in Kenya, Ghana, and Kerala over a sixteen-year period. Factor analysis reveals two (...) clusters of relationships, one interpretable as traditional scientific exchange, the other indicating mediated forms of collaboration. While collaboration increases in frequency, friendship declines. We interpret this shift as a consequence of communications technology that facilitates formal projects, reducing the affective dimension of professional association. (shrink)

Studies of AGL have frequently used training and test stimuli that might provide multiple cues for learning, raising the question what subjects have actually learned. Using a selected subset of studies on humans and non‐human animals, Trotter et al. demonstrate how a meta‐analysis can be used to identify relevant experimental variables, providing a first step in asssessing the relative contribution of design features of grammars as well as of species‐specific effects on AGL.

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular medium where (...) it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular medium where (...) it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This article discusses contemporary social psychological approaches to the social relations and appraisals associated with specific emotions; other people’s impact on appraisal processes; effects of emotion on other people; and interpersonal emotion regulation. We argue that single-minded cognitive perspectives restrict our understanding of interpersonal and group-related emotional processes, and that new methodologies addressing real-time interpersonal and group processes present promising opportunities for future progress.

Salient landmarks enhance route learning. We hypothesised that semantically salient nostalgic landmarks would improve route learning compared to non-nostalgic landmarks. In two experiments, participants learned a route through a computer-generated maze using directional arrows and wall-mounted pictures. On the test trial, the arrows were removed, and participants completed the maze using only the pictures. In the nostalgia condition, pictures were of popular music artists and TV characters from 5 to 10 years ago. In the control condition, they were recent pictures (...) of these same artists and characters. In Experiment 1, in the test trial, participants in the nostalgia condition completed the maze faster than controls. Experiment 2 conceptually replicated these findings and extended them by exploring boundary conditions. Participants had to learn two mazes sequentially. In Maze 1, we placed nostalgic/control landmarks only at non-decision points (whereas we placed them at decision points in Experiment 1). In Maze 2, we placed nostalgic/control landmarks at decision points during acquisition but removed them in the test trial (whereas they were present in the test trial in Experiment 1). In both mazes, participants in the nostalgia (compared to control) condition completed the test trial faster. (shrink)

In the 1960s and 1970s, scuba technology, underwater cameras, and documentarians revealed a long-hidden underwater world to the public. At this time oceanographic science was growing exponentially. Historians of the marine sciences have focused their studies of the period on institutional and military partnerships, and on the scientist-administrators who shaped oceanographic research institutions (such as the Scripps Institution of Oceanography, the Woods Hole Oceanographic Institution, and the British National Institute of Oceanography). Underwater habitat development during the 1960s and 1970s, however, (...) deserves greater attention than it has yet received, as it highlights a peculiar confluence of military, scientific, and popular interest, characteristic of the period, in the colonization of the seafloor. Existing accounts have focused on American habitats, notably Sealab and Tektite, since these were the largest and best funded. But this approach overemphasizes a Cold War narrative in which the sole protagonists of the habitat programs were the United States and the Soviet Union. At least 65 habitats were built between 1962 and 1991. Some were state-sponsored, with significant programs run by French, German, Japanese, and Canadian teams. This essay takes as a case study the Canadian Sublimnos habitat as well as the underwater exploration programs it helped launch in Newfoundland (Lora-I) and in the Arctic (Sub-Igloo). The Canadian case demonstrates that technological expertise and public enthusiasm for underwater exploration should not be solely understood with reference to Cold War interests of the two superpowers. Rather, the international range of habitat programs of the 1960s and 1970s reveals an expanding interest in the vertical underwater dimension that was fueled by numerous national scientific aims and territorial claims. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Response 2: “Pessimism of the Intellect, Optimism of the Will”Antonis BalasopoulosLet me begin with a few words on my title, which was chosen as reflecting the nature of the orientation of my work in the field of utopian studies and therefore also of my orientation toward the theme of this roundtable. As Francesca Antonini puts it in a recent essay, the phrase, which became associated with the work of (...) Antonio Gramsci though it originates in Romain Rolland, describes “the (seemingly contradictory) coexistence of a realistic description of the status quo, on the one hand, and a genuine commitment to the possibility of transforming reality, on the other.”1Anyone who has read Thomas More’s Utopia knows that Rolland’s and Gramsci’s formula very much describes that book’s bifurcation between a voice of relentless critique of what exists in Europe—and particularly in England—in More’s time (in Book 1) and a voice preoccupied with the description of an alternative, and arguably better, world (in Book 2). This bifurcation, it is equally well known, is part of the genetic material More’s book bequeathed to its successors, so that one calls a “utopia” a (mostly, though not always) literary text, where the “realistic description of the status quo” coexists with a vision arising out of a “commitment to the possibility of transforming reality”—admittedly in different admixtures and proportions of [End Page 544] the critical or negative and the anticipatory, projective or prefigurative elements. Though Ernst Bloch’s distinction between “cold” and warm” streams within Marxism is not identical to this first binary, it is certainly related to it, so that the “cold” stream is one that privileges the rational and analytical element (usually, I would propose, in relation to the part of the Marxist tradition we know as “critique of political economy”), while the “warm stream” is one that rather foregrounds that which relates to affect, to desire, hope, or fidelity to the transformative project (these are frequently correlated to those elements of Marxism that correspond to its also being a political and philosophically imbued creed).2 What follows here, then, explores the implications of the dialectical interplay between these two sets of oppositions—and hopefully justifies such insistence on dialectic itself.3To the extent that I can see, the basic themes and areas of concentration in my colleagues’ essays involve decolonizing utopian studies as a project; addressing, in that connection, the heterogeneity of utopianisms that emerge out of a number of marginalized subjectivities; the provenance of the questions of ecology, sustainability, animal life for the present and future of utopian studies (and to some degree, for utopianism’s past); and finally, the question of utopian forms of social activism and therefore also the search for spaces beyond the walls of academic insularity. These are important and largely interconnected questions, but I am afraid I will only have the space to touch on them briefly and sketchily here.In her cogent and multifaceted intervention, Caroline Edwards begins her reflections on the task of decolonizing utopian studies by noting the high investment of fin-de-siècle utopian fiction in notions of industrial progress, noting that such notions have involved “lasting damage” for “Black writers, artists, and thinkers.” Within this framework, she evokes Joseph R. Winters’s argument that “modern notions of progress and freedom are inherently flawed,” since they are founded on the oppressive traditions of capitalism and colonialism. In turn, this leads to an argument against the teleological futurism of most nineteenth-century utopias and in support of the deconstruction of “the idea of historical progress unfolding in Hegelian dialectical stages.” What is to replace this is a hauntological (after Derrida) conception of the relation between the present and the past, for which “the present is always a site of potential breaks and ruptures that can signify both dislocation and pain as well as novelty and possibility.” In a similar vein, Heather Alberro questions the teleological futurism of an earlier tradition of utopia, evoking Laurence Davis’s observation on the importance of [End Page 545] “neglected or suppressed possibilities for qualitatively better forms of life” within the “Now.” The desideratum is, again... (shrink)

ABSTRACTIn this paper I reassess the place of Plato’s Laws in the history of legal thought. The Laws has been traditionally considered to present a natural law theory of law. I argue instead that it presents a positivist account of the nature of law. Through analysis of some key passages of the Laws I argue that in that dialogue law is identified with conclusions of enkratic civic reason that may systematically conflict with precepts of substantive moral reason. I also argue (...) that in the Laws the rule of law is a precondition of a legal system but lacks inherent moral significance. For the rule of law to obtain there needs to be some compromise between the political interests of rulers and subjects which is grounded on political pragmatism and not on moral considerations. (shrink)

This paper provides an account of Kierkegaard’s central criticism of the Danish Hegelians. Contrary to recent scholarship, it is argued that this criticism has a substantive theoretical basis and is not merely personal or ad hominem in nature. In particular, Kierkegaard is seen as criticizing the Hegelians for endorsing an unacceptable form of intellectual elitism, one that gives them pride of place in the realm of religion by dint of their philosophical knowledge. A problem arises, however, because this criticism threatens (...) to apply to Kierkegaard himself. It is shown that Kierkegaard manages to escape this problem by virtue of the humorous aspect of his work. (shrink)

To many readers of The Prince, Machiavelli appears to be deeply un-Christian or even anti-Christian, a cynic who thinks rulers should use religion only to keep their subjects in check. But in Machiavelli's God, Maurizio Viroli, one of the world's leading authorities on Machiavelli, argues that Machiavelli, far from opposing Christianity, thought it was crucial to republican social and political renewal--but that first it needed to be renewed itself. And without understanding this, Viroli contends, it is impossible to comprehend Machiavelli's (...) thought. Viroli places Machiavelli in the context of Florence's republican Christianity, which was founded on the idea that the true Christian is a citizen who serves the common good. In this tradition, God participates in human affairs, supports and rewards those who govern justly, and desires men to make the earthly city similar to the divine one. Building on this tradition, Machiavelli advocated a religion of virtue, and he believed that, without this faith, free republics could not be established, defend themselves against corruption, or survive. Viroli makes a powerful case that Machiavelli, far from being a pagan or atheist, was a prophet of a true religion of liberty, a way of moral and political living that would rediscover and pursue charity and justice.The translation of this work has been funded by SEPS - Segretariato Europeo per le Pubblicazioni Scientifiche. (shrink)

To many readers of The Prince, Machiavelli appears to be deeply un-Christian or even anti-Christian, a cynic who thinks rulers should use religion only to keep their subjects in check. But in Machiavelli's God, Maurizio Viroli, one of the world's leading authorities on Machiavelli, argues that Machiavelli, far from opposing Christianity, thought it was crucial to republican social and political renewal--but that first it needed to be renewed itself. And without understanding this, Viroli contends, it is impossible to comprehend Machiavelli's (...) thought. Viroli places Machiavelli in the context of Florence's republican Christianity, which was founded on the idea that the true Christian is a citizen who serves the common good. In this tradition, God participates in human affairs, supports and rewards those who govern justly, and desires men to make the earthly city similar to the divine one. Building on this tradition, Machiavelli advocated a religion of virtue, and he believed that, without this faith, free republics could not be established, defend themselves against corruption, or survive. Viroli makes a powerful case that Machiavelli, far from being a pagan or atheist, was a prophet of a true religion of liberty, a way of moral and political living that would rediscover and pursue charity and justice.The translation of this work has been funded by SEPS - Segretariato Europeo per le Pubblicazioni Scientifiche. (shrink)

Recent scholarship has shown that the success of Pascal’s wager rests on precarious grounds. To avoid notorious problems, it must appeal to considerations such as what probability we assign to the existence of various gods and what religion we think provides the greatest happiness in this life. Rational judgments concerning these matters are subject to change over time. Some claim that the wager therefore cannot support a steadfast commitment to God. I argue that this conclusion does not follow. By drawing (...) upon the line of reasoning employed in getting married, I explain how unstable considerations can provide a sufficient rational foundation for a stable commitment. (shrink)

This study proposes that Neoplatonism, while not a modern philosophy, is philosophy in the modern sense. Lloyd analyzes the key structures that underlie the dogmas of the Neoplatonic world picture, including the concept of emanation, the return of the soul to the One, the place of mystical knowledge, epistemology, and Porphyry's theory of predication, and shows that they rest on original but intelligible concepts and arguments.

First published in 1961, this book considers Hume’s request to be judged solely by the acknowledged works of his maturity. It focuses on Hume’s first Inquiry in its own right as a separate book to the likes of his other works, such as the Treatise and the Dialogues, which are here only used as supplementary evidence when necessary. This approach brings out, as Hume himself quite explicitly wished to do, the important bearing of his more technical philosophy on matters of (...) religion and of world-outlook generally: "Be a philosopher; but amidst all your philosophy, be still a man.". (shrink)

Clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR‐associated protein (CRISPR/Cas) system has revolutionized genetic research in the life sciences. Four classes of CRISPR/Cas‐derived genome editing agents, such as nuclease, base editor, recombinase, and prime editor have been introduced for engineering the genomes of diverse organisms. The recently introduced prime editing system offers precise editing without many off‐target effects than traditional CRISPR‐based systems. Many researchers have successfully applied this gene‐editing toolbox in diverse systems for various genome‐editing applications. This review presents the mechanism (...) of prime editing and summarizes the details of the prime editing system applied in plants and mammalian cells for precise genome editing. We also discuss the advantages, limitations, and potential future applications of prime editing in these systems. This review enables the researcher to gain knowledge on prime editing tools and their potential applications in plants and mammalian cells. (shrink)

Decision outcomes sometimes result in negative emotions. This can occur when a decision appears to be wrong in retrospect, and/or when the obtained decision outcome does not live up to expectations. Regret and disappointment are the two emotions that are of central interest in the present article. Although these emotions have a lot in common, they also differ in ways that are relevant to decision making. In this article we review theories and empirical findings concerning regret and disappointment. We first (...) discuss how regret and disappointment differ with respect to their antecedent conditions, appraisals, and phenomenology. We also discuss possible behavioural consequences of experiencing these emotions. Next, we consider how the anticipation of regret and disappointment may influence decision making. We use regret and disappointment theory, developed by the economists Bell (1982, 1985), and Loomes and Sugden (1982, 1986, 1987), as a framework for our discussion. Finally, we argue that combining the theoretical approaches and research paradigms of behavioural decision theory with emotion theories will significantly increase our knowledge of antecedents and consequences of emotions. (shrink)

In comparison to the speech of the Laws, the dialectic between Crito and Socrates at the beginning of theCritohas received little attention. In this paper I argue that it contains an important philosophical message. It illustrates that the many's failure to follow Socrates' principles, like his principle of non-retaliation, is due to the intrinsic fragility of true beliefs. Though the many can understand Socrates' values and may accept his principles if he argues with them long enough, they may fail to (...) hold on to his principles when confronted with the difficulties of life. Crito's failure to deliberate Socratically at the beginning of theCritoexemplifies the many's predicament. (shrink)

This paper deals with Hobbes's theory of optical images, developed in his optical magnum opus, ‘A Minute or First Draught of the Optiques’, and published in abridged version in De homine. The paper suggests that Hobbes's theory of vision and images serves him to ground his philosophy of man on his philosophy of body. Furthermore, since this part of Hobbes's work on optics is the most thoroughly geometrical, it reveals a good deal about the role of mathematics in Hobbes's philosophy. (...) The paper points to some difficulties in the thesis of Shapin and Schaffer, who presented geometry as a ‘paradigm’ for Hobbes's natural philosophy. It will be argued here that Hobbes's application of geometry to optics was dictated by his metaphysical and epistemological principles, not by a blind belief in the power of geometry. Geometry supported causal explanation, and assisted reason in making sense of appearances by helping the philosopher understand the relationships between the world outside us and the images it produces in us. Finally the paper broadly suggests how Hobbes's theory of images may have triggered, by negative example, the flourishing of geometrical optics in Restoration England. (shrink)

Con el fin de desentrañar el papel que las más actuales corrientes filosóficas desempeñan en la educación, los autores de este libro parten de un crítico análisis de los acontecimientos de mayo del 68.Se intuyen dos vías de intervención de la filosofía sobre el pensamiento y la práctica educativa: por un lado, la tendencia anti constructivista a los discursos posmodernos, sistémicos y tecnológicos ; por otro, la persistencia del humanismo asentado ahora en el intento de prolongar la modernidad" y en (...) nuevas perspectivas tales como el pacifismo y el ecologismo. (shrink)

Regret and disappointment have in common the fact that they are experienced when the outcome of a decision is unfavourable: They both concern “what might have been”, had things been different. However, some regret and disappointment theorists regard the differences between these emotions as important, arguing that they differ with respect to the conditions under which they are felt, and how they affect decision making. The goal of the present research was to examine whether and how these emotions also differ (...) with respect to the way in which they are experienced. Participants were asked torecall aninstance of intense regret or disappointment andto indicate what they felt, thought, felt like doing, did, and were motivated to do during this experience (cf. Roseman, Wiest, & Swartz, 1994). Significant differences between regret and disappointment were found in every category. These differences were most pronounced for “action tendencies” (what participants felt like doing) and “emotivations” (what they were motivated to do). These results suggest that the two emotions have differential implications for future behaviour. (shrink)

Insults elicit intense emotion. This study tests the hypothesis that one's social image, which is especially salient in honour cultures, influences the way in which one reacts to an insult. Seventy-seven honour-oriented and 72 non-honour oriented participants answered questions about a recent insult episode. Participants experienced both anger and shame in reaction to the insult. However, these emotions resulted in different behaviours. Anger led to verbal attack (i.e., criticising, insulting in return) among all participants. This relationship was explained by participants’ (...) motivation to punish the wrongdoer. Shame, on the other hand, was moderated by honour. Shame led to verbal disapproval of the wrongdoers behaviour, but only among the honour-oriented participants. This relationship was explained by these participants’ motivation to protect their social image. By contrast, shame led to withdrawal among non-honour-oriented participants. (shrink)

The case for believing that aristotle thought perceptible qualities to be 'secondary' qualities or sense data has no firm grounds. Three types of argument for it are examined and claimed to be mistaken: the argument from the identity of act and object of perception, The argument from the "de anima" definitions, The argument from the formula 'receiving the form without the matter'. It is more likely that aristotle believed thinking to be involved in perception, So that his doubts about faculty (...) psychology are to be taken seriously. (shrink)

Many researchers believe the tremendous industrial development over the past two centuries is unsustainable because it has led to unintended ecological deterioration. Despite the ever-growing attention sustainable supply-chain management has received, most SSCM research and models look at the consequences, rather than the antecedents or motives of such responsible practices. The few studies that explore corporate motives have remained largely qualitative, and large-scale empirical analyses are scarce. Drawing on multiple theories and combining supply-chain and business ethics literature, we purport that (...) instrumental, relational, and moral motives are behind a firm’s engagement in SSCM practices. Specifically, we examine the links between corporate motives, SSCM practices, and firm performance. Using a sample of 259 supply-chain firms in Germany, we empirically test five hypothesized relationships. Our results reveal that relational and moral motives are key drivers, and that firms exhibiting high levels of moral obligations tend to outperform those primarily driven by amoral considerations. Findings of this study contribute to multiple literatures espousing sustainability management and can help policy makers, stakeholder groups, and scholars develop more robust strategies for encouraging firms to practice SSCM. (shrink)

In this article I analyze the speech of the Laws in Plato’s Crito from a jurisprudential perspective. More specifically I explore the Laws’ views about the authority of law. I offer new interpretations of their famous ‘persuade or obey’ alternative and of their arguments about their superior moral status and the agreements of the citizens with them. I also explore the rather neglected topic of the mental attitude towards their authority that they demand from the citizens and conclude with a (...) discussion of their understanding of the relation between law and morality. I approach the speech of the Laws as a historian of legal thought and try to locate their arguments firmly within both the context of the ancient Athenian legal system and the context of Platonic philosophy. (shrink)

The current legal status and medical ethics of routine or religious penile circumcision of minors is a matter of ongoing controversy in many countries. We focus on the United Kingdom as an illustrative example, giving a detailed analysis of the most recent British Medical Association guidance from 2019. We argue that the guidance paints a confused and conflicting portrait of the law and ethics of the procedure in the UK context, reflecting deeper, unresolved moral and legal tensions surrounding child genital (...) cutting practices more generally. Of particular note is a lack of clarity around how to apply the “best interests” standard—ordinarily associated with time-sensitive proxy decision making regarding therapeutic options for a medically unwell patient—to a parental request for a medically unnecessary surgery to be carried out on the genitalia of a healthy child. Challenges arise in measuring and assigning weights to intended sociocultural or religious/spiritual benefits, and even to health-related prophylactic benefits, and in balancing these against potential physical, functional, and psychosexual risks or harms. Also of concern are apparently inconsistent safeguarding standards being applied to children based on their birth sex categorization or gender of rearing. We identify and discuss recent trends in British and international medical ethics and law, finding gradual movement toward a more unified standard for evaluating the permissibility of surgically modifying healthy children's genitals before they can meaningfully participate in the decision. (shrink)

The present article commences analyzing the origins and influences of the religious discourse on the configuration of the modern constitutional discourse and the contributions of the jus-positivism in the consolidation of this sacred-civil language. The second issue is the definition of the U.S. Constitution as a mixed and not as a democratic constitution, with regard to the influences of Plato, Aristotle, Cicero and Polybius to the Drafters of the first modern constitutional text; stability and equilibrium took preference over democracy in (...) a wide sense. I also analyze how the Drafter’s decision has conditioned the modern constitutional system up to the present. (shrink)