The repair of chromosomal double‐strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51‐mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms.

The recombinational repair of chromosomal double‐strand breaks (DSBs) is of critical importance to all organisms, who devote considerable genetic resources to ensuring such repair is accomplished. In Saccharomyces cerevisiae, DSB‐mediated recombination can be initiated synchronously by the conditional expression of two site‐specific endonucleases, HO or I‐Scel. DNA undergoing recombination can then be extracted at intervals and analyzed. Recombination initiated by meiotic‐specific DSBs can be followed in a similar fashion. This type of ‘in vivo biochemistry’ has been used to describe several (...) discrete steps in two different homologous recombination pathways: gene conversion and single‐strand annealing. The roles of specific proteins during recombination can be established by examining DNA in strains deleted for the corresponding gene. These same approaches are now becoming available for the study of recombination in both higher plants and animals. Physical monitoring can also be used to analyze nonhomologous recombination events, whose mechanisms appear to be conserved from yeast to mammals. (shrink)

I reconcile the spatiotemporal location of repeatable artworks and impure sets with the non-location of natural numbers despite all three being varieties of abstract objects. This is possible because, while the identity conditions for all three can be given by abstraction principles, in the former two cases spatiotemporal location is a congruence for the equivalence relation featuring in the relevant principle, whereas in the latter it is not. I then generalize this to other ‘physical’ properties like shape, mass, and causal (...) powers. (shrink)

The purpose of the present paper is to formulate and resolve a certain puzzle surrounding God's existence and the standard attributes traditionally assigned to God.

In a recent symposium on Descartes' ontological argument, Norman Malcolm has restated a rather ingenious version of St Anse1m's ontological argument. 1 The purpose of the present paper is to assess the merits of this particular version of the ontological argument.

We study various aspects of the size, including the cardinality, of closed unbounded subsets of [λ]<κ, especially when λ = κ+n for n ε ω. The problem is resolved into the study of the size of certain stationary sets. Relative to the existence of an ω1-Erdös cardinal it is shown consistent that ωω3 < ωω13 and every closed unbounded subsetof [ω3]<ω2 has cardinality ωω13. A weakening of the ω1-Erdös property, ω1-remarkability, is defined and shown to be retained under a large (...) class of Easton-like forcings applied to ω1-Erdös cardinals. A class of reverse-Easton forcings preserving α-Erdösness is also described, with special attention to the establishment of □-principles. Article Outline. (shrink)

In 2012, a U.S. Institute of Medicine report called for a different approach to health care: “Left unchanged, health care will continue to underperform; cause unnecessary harm; and strain national, state, and family budgets.” The answer, they suggested, would be a “continuously learning” health system. Ethicists and researchers urged the creation of “learning health organizations” that would integrate knowledge from patient‐care data to continuously improve the quality of care. Our experience with an ongoing research study on atrial fibrillation—a trial known (...) as IMPACT‐AFib—gave us some insight into one of the challenges that will have to be dealt with in creating these organizations. Although the proposed educational intervention study placed no restrictions on what providers and health plans could do, the oversight team argued that the ethical principle of beneficence did not allow the researchers to be “bystanders” in relation to a control group receiving suboptimal care. In response, the researchers designed a “workaround” that allowed the project to go forward. We believe the experience suggests that what we call “bystander ethics” will create challenges for the kinds of quality improvement research that LHOs are designed to do. (shrink)

One of the contemporary results of Germany’s memorial conundrum is the rise of its “counter-monuments”: brazen, painfully self-conscious memorial spaces conceived to challenge the very premises of their being. On the former site of Hamburg’s greatest synagogue, at Bornplatz, Margrit Kahl has assembled an intricate mosaic tracing the complex lines of the synagogue’s roof construction: a palimpsest for a building and community that no longer exist. Norbert Radermacher bathes a guilty landscape in Berlin’s Neukölln neighborhood with the inscribed light of (...) its past. Alfred Hrdlicka began a monument in Hamburg to counter—and thereby neutralize—an indestructible Nazi monument nearby. In a suburb of Hamburg, Jochen Gerz and Esther Shalev-Gerz have erected a black pillar against fascism and for peace designed to disappear altogether over time. The very heart of Berlin, former site of the gestapo headquarters, remains a great, gaping wound as politicians, artists, and various committees forever debate the most appropriate memorial for this site.4 4. The long-burning debate surrounding projected memorials, to the Gestapo-Gelände in particular, continues to exemplify both the German memorial conundrum and the state’s painstaking attempts to articulate it. For an excellent documentation of the process, see Topographie des Terrors: Gestapo, SS und Reichssicherheitshauptamt auf dem “Prinz-Albrecht-Gelände,” ed. Reinhard Rürup . For a shorter account, see James E. Young, “The Topography of German Memory,” The Journal of Art 1 : 30. James E. Young is assistant professor of English and Judaic studies at the University of Massachusetts, Amherst. He is the author of Writing and Rewriting the Holocaust: Narrative and the Consequences of Interpretation and The Texture of Memory: Holocaust Memorials and Meaning in Europe, Israel, and America , from which this essay is drawn. He is also the curator of “The Art of Memory,” an exhibition at the Jewish Museum of New York. (shrink)

Moral distress is a major problem for nurses, other clinicians, and the health system itself. But if properly understood and responded to, it is also a promising guide for healthcare improvement. When individuals experience moral distress or burnout, their reports must be seen as crucial data requiring careful attention to the individuals and to the organization. Distress and burnout will often point to important opportunities for system improvements, which may in turn reduce the experience of distress. For this potential virtuous (...) cycle to happen, individuals must be able to articulate their concerns without fear of retribution, and organizational leaders must be able to listen in an undefensive, improvementoriented manner. (shrink)

Although leaders in the field of ethics have for many years pointed to the crucial role that organizations play in shaping healthcare ethics, organizational ethics remains a relatively undeveloped area of ethics activity. Clinical ethics committees are an important source of potential expertise, but new skills will be required. Clinical ethics committees seeking to extend their purview to organizational issues will have to respond to three challenges—how to gain sanction and support for addressing controversial and sensitive issues, how to develop (...) an acceptable process, and how to make a difference on the ground. The article presents practical suggestions for how clinical ethics committees meet these challenges. (shrink)

We study the I-ultrafilters on ω, where I is a collection of subsets of a set X, usually R or ω 1 . The I-ultrafilters usually contain the P-points, often as a small proper subset. We study relations between I-ultrafilters for various I, and closure of I-ultrafilters under ultrafilter sums. We consider, but do not settle, the question whether I-ultrafilters always exist.

While the prevalence of opioid use disorder among pregnant women has multiplied in the United States in the last decade, buprenorphine treatment for peripartum women with OUD has been administered to reduce risks of repeated cycles of craving and withdrawal. However, the maternal behavior and bonding in mothers with OUD may be altered as the underlying maternal behavior neurocircuit is opioid sensitive. In the regulation of rodent maternal behaviors such as licking and grooming, a series of opioid-sensitive brain regions are (...) functionally connected, including the ventral pallidum. In humans, these brain regions, interact with the supplementary motor area to regulate maternal behaviors and are functionally dysregulated by opioids. It is unclear how these brain regions respond to the emotions of their child for mothers receiving BT. In this functional magnetic resonance imaging pilot study in 22 mothers within the first postpartum year, including six mothers receiving BT and 16 non-OUD mothers as a comparison group, we devised a child face mirroring task in fMRI settings to assess maternal responses to pictures of facial expressions of own child and an unknown child in an empathic mirroring condition and a non-mirroring observation condition. In each condition, faces of neutral, ambiguous, distressed, and joyful expressions of each child were repeatedly displayed in a random order. The response of SMA during empathic mirroring vs. non-mirroring of own child was reduced among BT/OUD vs. CG. Within MBN, the left VP, critical for parental sensitivity, had a similar deficit. This study outlines potential mechanisms for investigating the risks of deficits in the neural responses to actual maternal sensitivity and parenting behavior in mothers with OUD, and potential targets for interventions that reduce stress and augment maternal behavior and child outcome. (shrink)

Jeremy Bentham was an ardent secularist convinced that society could be sustained without the support of religious institutions or beliefs. This is writ large in the commonly neglected books on religion he wrote and published during the last twenty-five years of his life. However his earliest writings on the subject date from the 1770s, when as a young man he first embarked on his calling as a legal theorist and social reformer. From that time on, religion was never far from (...) the centre of his thoughts. In Secular Utilitarianism, James Crimmins illustrates the nature, extent, and depth of Jeremy Bentham's concern with religion, from his Oxford days of first doubts to the middle years of quiet unbelief, and finally, the zealous atheism and secularism of his later life. Dr Crimmins provides an interpretation of Bentham's thought in which his religious views, hitherto of little interest to Bentham scholars, are shown to be integral: on the one hand intimately associated with the metaphysical, epistemological, and psychological principles which gave shape to his system as a whole, and on the other central to the development of his entirely secular view of society. (shrink)

James E. Bruce explores the relationship between morality and God’s free choices in the thought of Francis Turretin. The first book-length treatment of Turretin’s natural law theory, Rights in the Law provides an important theological backdrop to Early Modern moral and political philosophy. Turretin affirms Thomas Aquinas’s approach to the natural law, calling it the common opinion of the Reformed orthodox, but he develops it, too, by introducing a threefold scheme of right —divine, natural, and positive—to explain how change (...) within the law is possible. For example, God can change the specific day for Sabbath observance from Saturday to Sunday—from positive right—without changing the natural law precept that finite creatures ought to rest. Yet even with respect to the natural law God is still free. God can make a world in which there is no such thing as murder: he can choose not to make a world that contains such a thing as man. What God cannot do is make a murderable man. So God’s free choices determine the natural law insofar as the natural law is constituted by the nature of the things that God has chosen to create. (shrink)

A contribution to ongoing debates in the philosophy of science, aiming to reconceptualize the orientation of the subject. Mobilizing the literature, the authors seek to transform their insights into a new epistemological and ontological basis for studying the enterprise of science.

Unchanging God -- Simple God -- Simple God lost -- Eternal creator -- One God, three persons.

Current discussions of business ethics usually only consider deontological and utilitarian approaches. What is missing is a discussion of traditional teleology, often referred to as virtue ethics. While deontology and teleology are useful, they both suffer insufficiencies. Traditional teleology, while deontological in many respects, does not object to utilitarian style calculations as long as they are contained within a moral framework that is not utilitarian in its origin. It contains the best of both approaches and can be used to focus (...) on the individual''s role within an organization. More work is needed in exposing students and faculty to traditional teleology and its place in business ethic''s discussions. (shrink)

Women's experiences with sexual harassment were analyzed with three types of variables: occupational and workplace sex ratios, organizational policies and procedures for dealing with sexual harassment problems, and women's cultural status. Regression analyses revealed that extent of contact with men was a key predictor of incidence of harassment, number of different types of harrassment, sexual comments, sexual categorical remarks, and sexual materials. Gender predominance was a significant predictor of physical threats and sexual materials. Informational methods were less successful than proactive (...) methods in reducing incidents of sexual harassment. The analyses support two generalizations. The “contact hypothesis” tested and verified by Gutek and her colleagues provides a substantive understanding of our findings on workplace and occupational numerical predominance. Second, organizations that take a variety of steps to address sexual harassment are more apt to be successful in curtailing the problem than those relying mainly on “get out the word” techniques. (shrink)

Let κ denote a regular uncountable cardinal and NS the normal ideal of nonstationary subsets of κ. Our results concern the well-known open question whether NS fails to be κ + -saturated, i.e., are there κ + stationary subsets of κ with pairwise intersections nonstationary? Our first observation is: Theorem. NS is κ + -saturated iff for every normal ideal J on κ there is a stationary set $A \subseteq \kappa$ such that $J = NS \mid A = \{X \subseteq (...) \kappa:X \cap A \in NS\}$ . Turning our attention to large cardinals, we extend the usual (weak) Mahlo hierarchy to define "greatly Mahlo" cardinals and obtain the following: Theorem. If κ is greatly Mahlo then NS is not κ + -saturated. Theorem. If κ is ordinal Π 1 1 -indescribable (e.g., weakly compact), ethereal (e.g., subtle), or carries a κ-saturated ideal, then κ is greatly Mahlo. Moreover, there is a stationary set of greatly Mahlo cardinals below any ordinal Π 1 1 -indescribable cardinal. These methods apply to other normal ideals as well; e.g., the subtle ideal on an ineffable cardinal κ is not κ + -saturated. (shrink)

A series of topical philosophy studies aiming to publish original essays by foremost thinkers in their fields, with each volume confined to a main area of philosophical research.