Type II DNA topoisomerase activity is required to change DNA topology. It is important in the relaxation of DNA supercoils generated by cellular processes, such as transcription and replication, and it is essential for the condensation of chromosomes and their segregation during mitosis. In mammals this activity is derived from at least two isoforms, termed DNA topoisomerase IIα and β. The α isoform is involved in chromosome condensation and segregation, whereas the role of the β isoform is not yet clear. (...) DNA topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the last 10 years. BioEssays 20:215–226, 1998.© 1998 John Wiley & Sons, Inc. (shrink)

The aim of this article is to analyse Debret's work Voyage historique et pittoresque au Brésil and show that it is marked by the French Enlightenment. The text is divided into four parts, in addition to the introduction and conclusion: the first presents the historical context from which Debret was trained in painting and received the main influences in that art; the second deals with the technical aspects of writing the work; the third touches on the indigenous theme; the fourth (...) problematises the urban chronicle, focusing on the city of Rio de Janeiro; the fifth and final part takes up his central thesis: Debret looks at Brazil from the perspective of the Enlightenment. (shrink)

According to Bayesian orthodoxy, an agent should update---or at least should plan to update---her credences by conditionalization. Some have defended this claim by means of a diachronic Dutch book argument. They say: an agent who does not plan to update her credences by conditionalization is vulnerable (by her own lights) to a diachronic Dutch book, i.e., a sequence of bets which, when accepted, guarantee loss of utility. Here, I show that this argument is in tension with evidence externalism, i.e., the (...) view that an agent's evidence can entail non-trivial propositions about the external world. I argue that this tension casts doubt on the idea that diachronic Dutch books can be used to justify or vindicate updating plans. (shrink)

This paper establishes a dialogue between the later works of Wittgenstein, those of Cavell and the novels of J. M. Coetzee concerning the problem of violence, authority and the authoritative voice. By drawing on J. M. Coetzee's Waiting for the Barbarians and Diary of a Bad Year, the paper discusses lessons and insights on the nature of violence and the ways in which it can be accepted as “normal.” The term “normalization” is used in order to show how violence and (...) cruelty can become a “form of life” that develops according to its own actors, cultural practices and legitimacies. (shrink)

Rajan Gurukkal is a leading social scientist and is currently the Sundararajan Visiting Professor at Centre for Contemporary Studies, Indian Institute of Science. He has been the former Vice Chancellor, M. G. University, Kottayam, Kerala. An avid reader, critical theorist and a prolific writer, he has authored several monographs, research articles and has been actively engaged with several projects in association with UGC, the Ford Foundation to name a few. His research interests explore the historiographic dimensions and dialectical processes involving (...) the state and society. He can be reached at [email protected]. (shrink)

Recently, several epistemologists have defended an attractive principle of epistemic rationality, which we shall call Ur-Prior Conditionalization. In this essay, I ask whether we can justify this principle by appealing to the epistemic goal of accuracy. I argue that any such accuracy-based argument will be in tension with Evidence Externalism, i.e., the view that agent's evidence may entail non-trivial propositions about the external world. This is because any such argument will crucially require the assumption that, independently of all empirical evidence, (...) it is rational for an agent to be certain that her evidence will always include truths, and that she will always have perfect introspective access to her own evidence. This assumption is in tension with Evidence Externalism. I go on to suggest that even if we don't accept Evidence Externalism, the prospects for any accuracy-based justification for Ur-Prior Conditionalization are bleak. (shrink)

Recent work suggests that DNA replication origins are regulated by the number of multiple mini‐chromosome maintenance (MCM) complexes loaded. Origins are defined by the loading of MCM – the replicative helicase which initiates DNA replication and replication kinetics determined by origin's location and firing times. However, activation of MCM is heterogeneous; different origins firing at different times in different cells. Also, more MCMs are loaded in G1 than are used in S phase. These aspects of MCM biology are explained by (...) the observation that multiple MCMs are loaded at origins. Having more MCMs at early origins makes them more likely to fire, effecting differences in origin efficiency that define replication timing. Nonetheless, multiple MCM loading raises new questions, such as how they are loaded, where these MCMs reside at origins, and how their presence affects replication timing. In this review, we address these questions and discuss future avenues of research. (shrink)

In this article, I cast doubt on an apparent truism, namely, that if evidence is available for gathering and use at a negligible cost, then it’s always instrumentally rational for us to gather that evidence and use it for making decisions. Call this ‘value of information’ (VOI). I show that VOI conflicts with two other plausible theses. The first is the view that an agent’s evidence can entail non-trivial propositions about the external world. The second is the view that epistemic (...) rationality requires us to update our credences by conditionalization. These two theses, given some plausible assumptions, make room for rationally biased inquiries where VOI fails. I go on to argue that this is bad news for defenders of VOI. (shrink)

Intersexuality, particularly in the global South, remains an under‐researched field of study. In my in‐progress doctoral research project, I explore the cultural, social, and medical discourses that influence how key stakeholders such as healthcare providers make decisions about the sex and gender assignment of the intersex child in India. In this paper I interrogate some of these ideas around gender assignment of intersex people in India, paying particular attention to the context of son preference. I am interested in exploring how (...) decisions of gender assignment by medical professionals are guided by ideas of son preference. Focusing on four qualitative, semi‐structured, in‐depth interviews across two cities with medical doctors from different specializations, this paper is a preliminary attempt to examine some of the factors that guide medical professionals in making decisions about gender assignment of intersex children and explore the dynamics of the decision‐making process. Specifically, I explore the factors that inform doctors’ decision‐making and locate these decision‐making processes within the broader socio‐cultural context of India. (shrink)

Proteoglycan 4 (PRG4), first identified in synovial fluid, is an extracellular matrix structural protein in the joint implicated in reducing shear at the cartilage surface as well as controlling adhesion‐dependent synovial growth and regulating bulk protein deposition onto the cartilage. However, recent evidence suggests that it can bind to and effect downstream signaling of a number of cell surface receptors implicated in regulating the inflammatory response. Therefore, we pose the hypothesis: Does PRG4 regulate the inflammatory response and maintain tissue homeostasis? (...) Based on these novel findings implicating PRG4 as an inflammatory signaling molecule, we will present and discuss several hypotheses regarding potential mechanisms by which PRG4 may be able to regulate inflammation. If future studies can demonstrate that PRG4 is a potent inflammatory mediator, this will change current paradigms in the musculoskeletal and ophthalmological fields regarding the how the inflammatory microenvironment is regulated in these tissues and potentially others. (shrink)

In A Confection of Refutation (Khaṇḍanakhaṇḍakhādya), the twelfth-century philosopher and poet Śrīharṣa addresses a version of Meno’s paradox. This version of the paradox was well known in first millennium South Asia through the writings of two earlier Sanskrit philosophers, Śabarasvāmin (4th–5th century ce) and Śaṃkara (8th century ce). Both these thinkers proposed a solution to the paradox. I show how Śrīharṣa rejects this solution, and splits the old paradox into two new ones: the paradox of triviality and the paradox of (...) incoherence. I argue that these paradoxes are connected to Śrīharṣa’s broader pessimism about the possibility of successful rational inquiry into certain philosophical questions. (shrink)

An important question in epistemology is whether the KK principle is true, i.e., whether an agent who knows that p is also thereby in a position to know that she knows that p. We explain how a “transparency” account of self-knowledge, which maintains that we learn about our attitudes towards a proposition by reflecting not on ourselves but rather on that very proposition, supports an affirmative answer. In particular, we show that such an account allows us to reconcile a version (...) of the KK principle with an “externalist” or “reliabilist” conception of knowledge commonly thought to make that principle particularly problematic. (shrink)

In this paper I evaluate some recent virtue-ethical accounts of right action [Hursthouse 1999; Slote 2001; Swanton 2001]. I argue that all are vulnerable to what I call the insularity objection : evaluating action requires attention to worldly consequences external to the agent, whereas virtue ethics is primarily concerned with evaluating an agent's inner states. More specifically, I argue that insofar as these accounts are successful in meeting the insularity objection they invite the circularity objection : they end up relying (...) upon putatively virtue-ethical considerations that themselves depend on unexplained judgments of rightness. Such accounts thus face a dilemma that is characteristic of virtue-ethical accounts of right action. They avoid the insularity objection only at the cost of inviting the circularity objection: they become intuitively plausible roughly to the extent that they lose their distinctively virtue-ethical character. (shrink)

Human development can be seen as the process of giving more effective expression to human values. Modern business philosophy has a certain viewpoint or perspective on human potential based on the secular humanistic values of the west and the scientific theories on the nature of man and his evolution. We are bound to welcome the New Paradigm in Business because it opens the path for a decisive step forward in evolution from an authoritarian, mechanistic, Taylorian era to a freer and (...) a more humanistic ethos in business. (shrink)

BackgroundThe expectation of pandemic-induced severe resource shortages has prompted authorities to draft and update frameworks to guide clinical decision-making and patient triage. While these documents differ in scope, they share a utilitarian focus on the maximization of benefit. This utilitarian view necessarily marginalizes certain groups, in particular individuals with increased medical needs.Main bodyHere, we posit that engagement with the disability critique demands that we broaden our understandings of justice and fairness in clinical decision-making and patient triage. We propose the capabilities (...) theory, which recognizes that justice requires a range of positive capabilities/freedoms conducive to the achievement of meaningful life goals, as a means to do so. Informed by a disability rights critique of the clinical response to the pandemic, we offer direction for the construction of future clinical triage protocols which will avoid ableist biases by incorporating a broader apprehension of what it means to be human.ConclusionThe clinical pandemic response, codified across triage protocols, should embrace a form of justice which incorporates a vision of pluralistic human capabilities and a valuing of positive freedoms. (shrink)

Reidentification scepticism is the view that we cannot knowledgeably reidentify previously perceived objects. Amongst classical Indian philosophers, the Buddhists argued for reidentification scepticism. In this essay, I will discuss two responses to this Buddhist argument. The first response, defended by Vācaspati Miśra (9th century CE), is that our outer senses allow us to knowledgeably reidentify objects. I will claim that this proposal is problematic. The second response, due to Jayanta Bhaṭṭa (9th century CE), is that the manas or the inner (...) sense, functioning as a capacity of attention, helps us knowledgeably reidentify objects. I will explain how this second response answers the Buddhists’ challenge. (shrink)

Saitya Brata Das argues that in Kierkegaard's work we find a radical eschatological critique, not only of the liberal-humanist pathos of modernity but also the political theology of Carl Schmitt, that seeks to legitimise the sovereign power of the state by an appeal to a divine or theological foundation. Relating Kierkegaard's notion of 'Christianity without Christendom' to the Schellingian eschatological critique of sovereignty, he shows how Schelling's insistence on the eschatological difference between religion and politics is transformed and further intensified (...) in Kierkegaard's critique of historical reason. Such an exception without sovereignty, Das argues, is the very task of our contemporary time. (shrink)

How do senior business executives rank their preferences for various ethical principles? And how strongly do the executives believe in these principles? Also, how do these preference rankings relate to the way the executives see the future (wherein business decisions play out)? Research on these questions may provide us with an appreciation of the complexities of ethical behavior in management beyond the traditional issues concerning ethical decision-making in business. Based on a survey of 585 vice presidents of U.S. businesses it (...) was found that: (1) there is a distinct set of principles of ethical conduct that is considered favorable as opposed to another set considered unfavorable among a comprehensive list of 14 ethical principles; (2) the executives believed overwhelmingly that their own individual ethical preferences are better than those of other executives; (3) the strength of their preferences for ethical principles is associated with whether the executives are relatively near-future oriented or more distant-future oriented; and (4), there are very few significant differences in terms of gender, age, education level, private/public education, prestigious/other schools, business/non-business academic backgrounds, and length of job experience. Implications of these findings are discussed. (shrink)

Paul of Aegina's (fl.c. 630)Pragmateiais the only extant Greek medical text from antiquity that discusses the extraction of arrows and small missiles. In his book on surgery, Paul details how to extract arrows according to their properties and the parts of the body which they have wounded (6.88). He prefaces his instructions by describing how arrows differ in their material, figure, size, number, mode, and power. Paul's account of arrow varieties appears to reflect the environment of his medical practice, seventh-century (...) Alexandria, for he refers to Egyptian arrow types when listing the material composition and sizes of different arrows. (shrink)

In the original publication of the article, on page 20, the section heading should be “Gaṅgeśa on Testimony and Epistemic Luck” instead of “Testimony and Epistemic Luck”.