Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells face a special challenge, (...) because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. (shrink)

DNA double‐strand breaks (DSBs) are extremely hazardous lesions for all DNA‐bearing organisms and the mechanisms of DSB repair are highly conserved. In the eukaryotic mitotic cell cycle, DSBs are often present following DNA replication while, in meiosis, hundreds of DSBs are generated as a prelude to the reshuffling of the maternally and paternally derived genomes. In both cases, the DSBs are repaired by a process called homologous recombinational repair (HRR), which utilises an intact DNA molecule as the repair template. Mitotic (...) and meiotic HRR are managed by ‘checkpoints’ that inhibit cell division until DSB repair is complete. Here we attempt to summarise the substantial recent progress in understanding the checkpoint management of HRR in mitosis (focussing mainly on mammals) and then go on to use this information as a framework for understanding the presumed checkpoint management of HRR in mammalian meiosis. BioEssays 29:974–986, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Book reviewed in this article: Just War Tradition and the Restraint of War: A Moral and Historical Inquiry. By James Turner Johnson.

The study of anarchism as a philosophical, political, and social movement has burgeoned both in the academy and in the global activist community in recent years. Taking advantage of this boom in anarchist scholarship, Nathan J. Jun and Shane Wahl have compiled twenty-six cutting-edge essays on this timely topic in New Perspectives on Anarchism.

Hubert Dreyfus has argued that cases of absorbed bodily coping show that there is no room for self-awareness in flow experiences of experts. In this paper, I argue against Dreyfus’ maxim of vanishing self-awareness by suggesting that awareness of agency is present in expert bodily action. First, I discuss the phenomenon of absorbed bodily coping by discussing flow experiences involved in expert bodily action: merging into the flow; immersion in the flow; emergence out of flow. I argue against the claim (...) that flow experience does not involve an awareness of agency for each of these features, while conceding that fluent agency does not involve self-awareness in the thetic sense. I challenge the assumption that the awareness of fluent agency must be understood in terms of a thetic awareness of agency. Instead, I develop an Anscombean account of the awareness of fluent agency in terms of the phenomenal character of knowing one’s aims. I respond to the challenge that if an Anscombean account of the awareness of agency is to succeed, then agents must be able to answer Anscombean questions. I consider the objection that awareness of agency is not a form of self-awareness by outlining an account of self-awareness as self-synthesis that is distinct from self-perception and self-ascription, but which makes room for self-awareness in expert bodily action. (shrink)

In this paper, we report on the development and validity of the Professional Decision-Making in Research measure, a vignette-based test that examines decision-making strategies used by investigators when confronted with challenging situations in the context of empirical research. The PDR was administered online with a battery of validity measures to a group of NIH-funded researchers and research trainees who were diverse in terms of age, years of experience, types of research, and race. The PDR demonstrated adequate reliability and parallel form (...) correlation. As hypothesized, the PDR was significantly negatively correlated with narcissism, cynicism, moral disengagement, and compliance disengagement; it was not correlated with socially desirable responding. In regression analysis, the strongest predictors of higher PDR scores were low compliance disengagement, speaking English as a native language, conducting clinical research with human subjects, and low levels of narcissism. Given that the PDR was written at an eighth grade reading level to be suitable for use with English as a second language participants and that only one-fourth of items focused on clinical research, further research into the possible roles of culture and research ethics training across specialties is warranted. This initial validity study demonstrates the potential usefulness of the PDR as an educational outcome assessment measure and a research instrument for studies on professionalism and integrity in research. (shrink)

Based on the author's more than 50 years of experience as a professional historian in academic and other capacities, Being a Historian is addressed to both aspiring and mature historians. It offers an overview of the state of the discipline of history today and the problems that confront it and its practitioners in many professions. James M. Banner, Jr. argues that historians remain inadequately prepared for their rapidly changing professional world and that the discipline as a whole has yet (...) to confront many of its deficiencies. He also argues that, no longer needing to conform automatically to the academic ideal, historians can now more safely and productively than ever before adapt to their own visions, temperaments, and goals as they take up their responsibilities as scholars, teachers, and public practitioners. Critical while also optimistic, this work suggests many topics for further scholarly and professional exploration, research, and debate. (shrink)

A collection of fourteen essays which provide an overview of the argument for intelligent design, with diagrams, explanations, and relevant quotations.

In lieu of an abstract, here is a brief excerpt of the content:Editors’ NoteJames M. DuBois, Ana S. Iltis, and Heidi A. WalshFrom childhood, David Slakter had undergone tests and invasive procedures to monitor his nephritis. It was not a surprise when in 2015, doctors told him he needed a kidney transplant. The wife of a childhood friend was a close match and gave him one of her kidneys. Before his transplant, aerobic exercise was difficult; a few months after transplant, (...) Slakter could ride his bike, hike, and work out with a personal trainer. He no longer had to weigh food or gauge his potassium consumption, a concern for people with kidney failure. For Slakter, “life post-transplant has been a significant improvement.”Individuals or family members of those who have received an organ transplant from a living or deceased donor share their stories in this issue of Narrative Inquiry in Bioethics. The symposium is titled “Receiving the Gift of Life: Stories from Organ Transplant Recipients.” Organ transplantation can extend an individual’s life by decades. It can also greatly improve an individual’s quality of life, as was Slakter’s experience. At the same time, organ transplantation is expensive and stressful. Recipients can experience complications, including organ rejection, and there are few appealing alternatives.After her heart transplant, author Leilani R. Graham required four open-heart surgeries, ECMO, and an intra-aortic balloon pump. She experienced delirium, necrotizing pneumonia, and severe muscular atrophy that required her to re-learn how to walk. She struggled with weight gain, explosive mood swings, hair loss, and was terrified that her body would reject the new heart. For Graham, “[Transplant] was not the miracle [she] was hoping for.” Graham says she felt unprepared for and inadequately informed about what to expect after her transplant, which left her “battered, beaten, and bruised” with a 12-inch line from neck to navel and “bullet holes” up and down her torso from the chest tubes. When reflecting on her experience post-transplant, Graham says, “It wasn’t the physical trauma that hurt the most. It was that no one seemed surprised [by the aftereffects of transplant].” Seemingly no one, that is except Graham, who calls on transplant providers to “prioritize empathy.”The symposium editors are Jason T. Eberl and Tristan McIntosh. Three commentary articles, written by Macey Leigh Levan, Heather Lannon, and Vidya A. Fleetwood, Roslyn B. Mannon & Krista L. Lentine, offer important insights into the authors’ stories. The editors thank Mid-America Transplant, the UCSF Lung Transplant Program, Donor Connect, William L. Freeman, MD, MPH, MJIL, CIP, Janet Monk, and the individuals who gave anonymous donations to support the publication of this issue, an open-access VOICES edition of the symposium, and accompanying teaching guides.The research article in this issue, “‘A Shell of My Former Self’: Using Figurative Language to Promote Communication about Patient Suffering,” was written by Tyler Tate, Elizabeth Stein, and Robert A. Pearlman. The relief of suffering is a primary goal of medicine. However, the authors note that clinicians often miss or ignore suffering because they focus on the causes rather than the experience of suffering, or the subjective nature of suffering makes it difficult to discuss. The authors believe that “the key to communicating about suffering lies in finding [End Page vii] the right kind of words to describe the experience” and say that figurative language offers a promising approach. In their research, the authors performed qualitative analysis on 52 works of literature and identified 254 excerpts of figurative language with themes of non-physical or psychological suffering. The authors found 13 salient themes: brokenness, diminishment, disorientation, drowning, emptiness, imprisonment, battle, darkness, isolation, invisibility, lifelessness, punishment, and torture. The authors reiterate that developing a shared language of suffering could foster a therapeutic patient-clinician relationship and improve clinicians’ ability to recognize and address a patient’s experience of suffering.María Susana Ciruzzi wrote the first of two case studies included in this issue. “The Sword of King Solomon” addresses a tragic and difficult subject—how to navigate the situation posed by conjoined twins when “any decision will produce damage and suffering.” The case involves two infant male patients born at 37 weeks gestation as omphalo-ischiopagus conjoined twins... (shrink)

This book defends the view that any adequate account of rational decision making must take a decision maker's beliefs about causal relations into account. The early chapters of the book introduce the non-specialist to the rudiments of expected utility theory. The major technical advance offered by the book is a 'representation theorem' that shows that both causal decision theory and its main rival, Richard Jeffrey's logic of decision, are both instances of a more general conditional decision theory. The book solves (...) a long-standing problem for Jeffrey's theory by showing for the first time how to obtain a unique utility and probability representation for preferences and judgements of comparative likelihood. The book also contains a major new discussion of what it means to suppose that some event occurs or that some proposition is true. The most complete and robust defence of causal decision theory available. (shrink)

Histone deacetylase inhibitors (HDACi) are in clinical trials against a variety of cancers. Despite early successes, results against the more common solid tumors have been mixed. How is it that so many cancers, and most normal cells, tolerate the disruption caused by HDACi‐induced protein hyperacetylation? And why are a few cancers so sensitive? Here we discuss recent results showing that human cells mount a coordinated transcriptional response to HDACi that mitigates their toxic effects. We present a hypothetical signaling system that (...) could trigger and mediate this response. To account for the existence of such a response, we note that HDACi of various chemical types are made by a variety of organisms to kill or suppress competitors. We suggest that the resistance response in human cells is a necessary evolutionary consequence of exposure to environmental HDACi. We speculate that cancers sensitive to HDACi are those in which the resistance response has been compromised by mutation. Identifying such mutations will allow targeting of HDACi therapy to potentially susceptible cancers. (shrink)

There exists a common view that for theories related by a ‘duality’, dual models typically may be taken ab initio to represent the same physical state of affairs, i.e. to correspond to the same possible world. We question this view, by drawing a parallel with the distinction between ‘interpretational’ and ‘motivational’ approaches to symmetries.

Contributions in modern theoretical physics and chemistry on the behavior of nonlinear systems, exemplified by Ilya Prigogine's work on the thermodynamics of open systems, attract growing attention in economics. Our purpose here is to relate the new orientation in the natural sciences to a particular nonorthodox strand of thought within economics. All that is needed for this purpose is some appreciation of the general thrust of the enterprise, which involves a shift of perspective from the determinism of conventional physics to (...) the nonteleological open-endedness, creative, and nondetermined nature of evolutionary processes. (shrink)

The pragmatic character of the Dutch book argument makes it unsuitable as an "epistemic" justification for the fundamental probabilist dogma that rational partial beliefs must conform to the axioms of probability. To secure an appropriately epistemic justification for this conclusion, one must explain what it means for a system of partial beliefs to accurately represent the state of the world, and then show that partial beliefs that violate the laws of probability are invariably less accurate than they could be otherwise. (...) The first task can be accomplished once we realize that the accuracy of systems of partial beliefs can be measured on a gradational scale that satisfies a small set of formal constraints, each of which has a sound epistemic motivation. When accuracy is measured in this way it can be shown that any system of degrees of belief that violates the axioms of probability can be replaced by an alternative system that obeys the axioms and yet is more accurate in every possible world. Since epistemically rational agents must strive to hold accurate beliefs, this establishes conformity with the axioms of probability as a norm of epistemic rationality whatever its prudential merits or defects might be. (shrink)

I take it as my assignment to criticize the Gauthier enterprise. At the outset, however, I should express my general agreement with David Gauthier's normative vision of a liberal social order, including the place that individual principles of morality hold in such an order. Whether the enterprise is, ultimately, judged to have succeeded or to have failed depends on the standards applied. Considered as a coherent grounding of such a social order in the rational choice behavior of persons, the enterprise (...) fails. Considered as an extended argument implying that persons should adopt the moral stance embodied in the Gauthier structure, the enterprise is, I dunk, largely successful. Considered as a set of empirically falsifiable propositions suggesting that persons do, indeed, choose as the Gauthier precepts dictate, the enterprise offers Humean hope rather than Hobbesian despair. (shrink)

Physician-Assisted Death is the eleventh volume of Biomedical Ethics Reviews. We, the editors, are pleased with the response to the series over the years and, as a result, are happy to continue into a second decade with the same general purpose and zeal. As in the past, contributors to projected volumes have been asked to summarize the nature of the literature, the prevailing attitudes and arguments, and then to advance the discussion in some way by staking out and arguing forcefully (...) for some basic position on the topic targeted for discussion. For the present volume on Physician-Assisted Death, we felt it wise to enlist the services of a guest editor, Dr. Gregg A. Kasting, a practicing physician with extensive clinical knowledge of the various problems and issues encountered in discussing physician assisted death. Dr. Kasting is also our student and just completing a graduate degree in philosophy with a specialty in biomedical ethics here at Georgia State University. Apart from a keen interest in the topic, Dr. Kasting has published good work in the area and has, in our opinion, done an excellent job in taking on the lion's share of editing this well-balanced and probing set of essays. We hope you will agree that this volume significantly advances the level of discussion on physician-assisted euthanasia. Incidentally, we wish to note that the essays in this volume were all finished and committed to press by January 1993. (shrink)

This study examines the influence of ethics instruction, religiosity, and intelligence on cheating behavior. A sample of 230 upper level, undergraduate business students had the opportunity to increase their chances of winning money in an experimental situation by falsely reporting their task performance. In general, the results indicate that students who attended worship services more frequently were less likely to cheat than those who attended worship services less frequently, but that students who had taken a course in business ethics were (...) no less likely to cheat than students who had not taken such a course. However, the results do indicate that the extent to which taking a business ethics course influenced cheating behavior was moderated by the religiosity and intelligence of the individual student. In particular, while students who were highly religious were unlikely to cheat whether or not they had taken a business ethics course, students who were not highly religious demonstrated less cheating if they had taken a business ethics course. In addition, the extent of cheating among highly intelligent students was significantly reduced if such students had taken a course in business ethics. Likewise, individuals who were highly intelligent displayed significantly less cheating if they were also highly religious. The implications of these findings are discussed. (shrink)