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)

Software application ontologies have the potential to become the keystone in state-of-the-art information management techniques. It is expected that these ontologies will support the sort of reasoning power required to navigate large and complex terminologies correctly and efficiently. Yet, there is one problem in particular that continues to stand in our way. As these terminological structures increase in size and complexity, and the drive to integrate them inevitably swells, it is clear that the level of consistency required for such navigation (...) will become correspondingly difficult to maintain. While descriptive semantic representations are certainly a necessary component to any adequate ontology-based system, so long as ontology engineers rely solely on semantic information, without a sound ontological theory informing their modeling decisions, this goal will surely remain out of reach. In this paper we describe how Language and Computing nv (L&C), along with The Institute for Formal Ontology and Medical Information Sciences (IFOMIS), are working towards developing and implementing just such a theory, combining the open software architecture of L&C’s LinkSuiteTM with the philosophical rigor of IFOMIS’s Basic Formal Ontology. In this way we aim to move beyond the more or less simple controlled vocabularies that have dominated the industry to date. (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)

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)

Four views concerning environmental disobedience are discussed in this chapter, focusing on the moral justification of lawbreaking on behalf of natural environments. The traditional view suggests that accounts of ordinary civil disobedience understood through the Rawlsian tradition can be extended to capture cases of environmental disobedience. The revisionary view argues that the concept of civil disobedience needs to be revised in order to account for environmental disobedience, ecosabotage in particular. The radical view militates against basic assumptions of civil disobedience to (...) argue that ecosabotage counts as forms of civil disobedience. The envisionary view suggests that environmental disobedience is best understood as a creative performance, a type of beautiful trouble or creative disruption that expresses environmental values that we must use the moral imagination to understand. (shrink)

The Objective of “Tranquillity’s Secret” Is To Present A New More Veridical Way Of Understanding The World, And The Meditation Technique And Its Unexcelled Support That Directly Leads One To See The World Differently. -/- In our rational attempts to understand ourselves and our world today, it is the case that in comparison to matter, which is so definite, measurable, actual, and sometimes literally concrete, we have ‘mind’ and ‘consciousness’, which is exactly the opposite: it is indefinite, unmeasurable, undiscoverable, and (...) abstract. And yet, it is the reverse within our lived experience in which it is our being aware that is actual, indisputable, irrefutable, true, and well-grounded, while matter is only an abstraction from our experiences, that is wholly contingent, and about which everything is unsure. So why do we search for ‘consciousness’ by reasoning about the world, rather than meditating upon our immediate lived experience? ‘Consciousness’ is an abstraction taken from our experience, so we cannot use ‘consciousness’ to explain experience. A contemplative science would. -/- The meditation technique that Tranquillity’s Secret presents uses Inner Spontaneous Sound as its support. These uncaused sounds which are always available to meditate with, have no material basis, and so their very presence calls into question our faith that only matter matters. These sounds appear in different forms in the myriad of contemplative traditions which have employed them for millennia and have universally acknowledged them as the most efficacious path to a direct experience of the nature of Reality. Unfortunately, during modern times, the correct use of these sounds has been almost lost, along with the reasons why they were claimed to be so highly effective. The primary condition for this loss is the mechanical materialism which frames what is allowable for thought, and constrains our reasoning to only consider reductionist mechanical explanations in every case. Even those who believe they have escaped from the limitations of this understanding, continue to be enframed because our language has been structured by it, so that there is no true escape via a simple substitution or redefinition of concepts. Instead, Tranquillity’s Secret presents a new understanding that supersedes mechanical materialism and its paradigm of physical causality. It begins with an acceptance that Time is only a formalism, and does not exist in the sense of either an arrow or a stream. This leads to a radical reorientation of what it means to be aware and conscious, and the discovery of a revolutionary understanding of coherent Responsive Naturing that supplants the never-solved paradoxes of ‘consciousness’ and ‘causal change over time’ with coherent and immediate processual reconfigurations based upon contextual conditions, potentials, and probabilities — and the recognition of each reconfiguration. -/- Thus, Responsive Naturing provides a sound foundation for veridical science, so that both science and spirituality can be founded upon a common understanding of ‘how things work’. This empowers us in ways that our disjointed and parochial schools of thought lock us out of completely, while opening up new possible methods of looking at problems and finding solutions across disciplines. (shrink)

On reading Plato -- Socrates' story of death and life -- Theaetetus: boy-testing in Lotus land -- Sophist: casts of the net -- Sophist: another miss? -- Politician: another effort to snare Socrates-Odysseus -- Socrates is convicted by a jury of young children.

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

Many philosophers in the ancient world shared a unitary vision of philosophy – meaning 'love of wisdom' – not just as a theoretical discipline, but as a way of life. Specifically, for the late Neoplatonic thinkers, philosophy began with self-knowledge, which led to a person's inner conversion or transformation into a lover, a human being erotically striving toward the totality of the real. This metamorphosis amounted to a complete existential conversion. It was initiated by learned guides who cultivated higher and (...) higher levels of virtue in their students, leading, in the end, to their vision of the Good, or the One. In this book, James M. Ambury closely analyses two central texts in this tradition: the commentaries by Proclus (412–485 AD) and Olympiodorus (495–560 AD) on the Platonic Alcibiades I. Ambury's powerful study illuminates the way philosophy was conceived during a crucial period of its history, in the lecture halls of late antiquity. (shrink)

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)

Explores the theories of democratic individualism articulated in the works of the American transcendentalist writer Ralph Waldo Emerson, pragmatic philosophers William James and John Dewey, and African-American novelist and essayist Ralph Ellison.