Mitotic recombination is a repair process which is known to repair double strand breaks and to fill double‐strand gaps by copying a homologous sequence. Meiotic recombination is a process of heteroduplex formation which sometimes generates crossovers. Evidence is presented that the later stages of meiotic recombination have some characteristics of mitotic repair recombination, leading to the conclusion that mismatch repair may be a recombinogenic repair process. The evidence suggests that the recombinational repair process generates hetero‐duplex bubbles which can move. Some (...) bubbles become crossovers. Others cease to exist, perhaps because topoisomerase activity breaks them down. (shrink)

Evolutionary theory assumed that mutations occur constantly, gradually, and randomly over time. This formulation from the “modern synthesis” of the 1930s was embraced decades before molecular understanding of genes or mutations. Since then, our labs and others have elucidated mutation mechanisms activated by stress responses. Stress‐induced mutation mechanisms produce mutations, potentially accelerating evolution, specifically when cells are maladapted to their environment, that is, when they are stressed. The mechanisms of stress‐induced mutation that are being revealed experimentally in laboratory settings provide (...) compelling models for mutagenesis that propels pathogen–host adaptation, antibiotic resistance, cancer progression and resistance, and perhaps much of evolution generally. We discuss double‐strand‐break‐dependent stress‐induced mutation in Escherichia coli. Recent results illustrate how a stress response activates mutagenesis and demonstrate this mechanism's generality and importance to spontaneous mutation. New data also suggest a possible harmony between previous, apparently opposed, models for the molecular mechanism. They additionally strengthen the case for anti‐evolvability therapeutics for infectious disease and cancer. (shrink)

An educational provision for young children with autism that offers intensive behavioural intervention based on the principles of Applied Behaviour Analysis (ABA), within an early years mainstream school setting in the UK, is described. The ABA Class at Westwood School is a collaborative project between the School of Psychology, Bangor University, two Local Education Authorities in North East Wales (Flintshire and Wrexham) and the local NHS Trust. Using two case examples, two important features of mainstream education for children with autism (...) are considered: access to the National Curriculum, and inclusion with peers in mainstream settings. Standardised test data on outcomes for these children over the initial 12 months of their educational placements are also provided. (shrink)

The authors respond to a letter by Mitchell Berger in the March‐April 2024 issue of the Hastings Center Report concerning their essay “Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines.”.

Most donated organs in the United States come from brain dead donors, while a small percentage come from patients who die in “controlled,” or expected, circumstances, typically after the family or surrogate makes a decision to withdraw life support. The number of organs available for transplant could be substantially if donations were permitted in “uncontrolled” circumstances–that is, from people who die unexpectedly, often outside the hospital. According to projections from the Institute of Medicine, establishing programs permitting “uncontrolled donation after circulatory (...) determination of death,” or uDCDD, throughout the United States has the potential to provide 22,000 more donation opportunities annually. In contrast, U.S. controlled donation after circulatory determination of death, or cDCDD, cases have increased progressively over the past decade from 87 to 848 donors, but currently account for only 10.6 percent of all deceased donors. Following the IOM recommendations, several projects exploring the feasibility of uDCDD were funded by the federal government, including a grant from the Health Resources and Services Administration that supported a pilot project in New York City in which the authors of this article participated.A key feature of our protocol, and indeed of many uDCDD protocols, is the initiation of preservation methods such as chest compressions and extracorporeal membrane oxygenation shortly after death in order to perfuse and preserve the donor's organs. Critics of uDCDD argue that the means of determining death deviates from generally ascribed principles. They assert that reinstituting circulation in order to preserve organs has the effect of “undoing” the prior determination of death. The result is that cDCDD is widely accepted and practiced routinely even though it only marginally increases the number of organs available for transplantation, and uDCDD is widely considered unacceptable despite being ethically embraced and proven to significantly increase organ donation opportunities in other countries. This article explores the evolution of this counterintuitive state of affairs and calls for a policy that, in line with the IOM report, allows for both cDCDD and uDCDD protocols. (shrink)

The report by Barbara Bierer and Mark Barnes highlights the complexities experienced by institutions that conduct Public Health Service‐funded research involving human subjects and that need to negotiate the requirements of two sets of federal regulations: 45 C.F.R. 46, covering protections for human research subjects, and 42 C.F.R. 93, the PHS policies on research misconduct. As the nation's single largest sponsor of biomedical and behavioral research, the National Institutes of Health seeks to exemplify and promote human research protections and the (...) highest level of scientific integrity, public accountability, and social responsibility in the conduct of science. The NIH is committed to protecting the rights and welfare of research participants and to upholding integrity standards for research supported with public funds. However, human subjects protections must always take priority. (shrink)

The Covid‐19 pandemic highlighted the need to examine public trust in the U.S. Food and Drug Administration (FDA) vaccine approval process and the role of political influence in the FDA's decisions. Ensuring that the FDA is itself trustworthy is important for justifying public trust in its actions, like vaccine approvals, thereby promoting public health. We propose five conditions of trustworthiness that the FDA should meet when it reviews vaccines, even during emergencies: consistency with rules, proper expert or political decision‐makers, proper (...) decision‐making and noninterference, connection to public preference, and transparency of both reasons and procedures. The five conditions provide a road map of procedural and substantive requirements, which the FDA has variably implemented, focused on ensuring appropriate influence of political interests. While being a trustworthy agency cannot guarantee the public's trust, implementing these conditions builds a groundwork for public trust. (shrink)

The release of genetically engineered organisms into the shared environment raises scientific, ethical, and societal issues. Using some form of democratic deliberation to provide the public with a voice on the policies that govern these technologies is important, but there has not been enough attention to how we should connect public deliberation to the existing regulatory process. Drawing on lessons from previous public deliberative efforts by U.S. federal agencies, we identify several practical issues that will need to be addressed if (...) relevant federal agencies are to undertake public deliberative activities to inform decision‐making about gene editing in the wild. We argue that, while agencies may have institutional capacity to undertake public deliberative activities, there may not be sufficient political support for them to do so. Advocates of public deliberation need to make a stronger case to Congress about why federal agencies should be encouraged and supported to conduct public deliberations. (shrink)

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human‐nonhuman chimeric research. Led by bioethics researchers working closely with an (...) interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human‐nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics’ previous focus on human‐centered questions about the ethics of “humanization” and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less‐siloed governance and oversight and more‐comprehensive public communication. (shrink)

Book reviewed in this article: The Gene Factory. By John Elkington. In the Name of Eugenics: Genetics and the Uses of Human Heredity. By Daniel J. Kevles. Broken Code: The Exploitation of DNA. By Marc Lappé.

Inleidend overzicht van de wijsgerige ethiek.

Speeches delivered in Tamil at various schools in Tamil Nadu, during 2010-2015, by A.P.J. Abdul Kalam, 1931-2015, former President of India.

Philip J. Ivanhoe's richly annotated translation of this classic work is accompanied by his engaging interpretation and commentary, a lucid introduction, and a Language Appendix that compares eight classic translations of the opening passage of the work and invites the reader to consider the principles upon which each was rendered.

This new edition offers expanded selections from the works of Kongzi, Mengzi, Zhuangzi, and Xunzi ; two new works, the dialogues _Robber Zhi_ and _White Horse_; a concise general introduction; brief introductions to, and selective bibliographies for, each work; and four appendices that shed light on important figures, periods, texts, and terms in Chinese thought.

This volume contains papers and abstracts of papers delivered at the colloquium at Tihany, Hungary in 1962. There were seven sections; mathematical logic, computers and automata theory, circuit theory, mathematical linguistics, computers and programming, applications of computers in economics, artificial intelligence. Among the more interesting—to the reviewer—were these papers: one by Church concerning an independence problem in recursive arithmetic; Muller—characterizing classes of recursive functions; a long and philosophically stimulating study by Watanabe on a formalization of inductive logic; Kiefer—applications of set (...) theoretic techniques in linguistics; Abraham and Salapina—recognition of synonymity by machine; Gelernter—problem-solving graphs and heuristic programming. A number of papers which were read are not included in this volume.—P. J. M. (shrink)

This is a collection of papers, all but one of which were previously published, by one of England's leading logicians. Goodstein has described his position in the philosophy of mathematics as that of a "constructive formalist": leaning toward the Hilbert school, but emphasizing the constructive nature of mathematical entities. The papers are more or less technical and symbolic; those most difficult are "The Nature of Mathematics," "The Decision Problem," and "The Definition of Number." Other titles are "Proof by Reductio ad (...) Absurdum," "Logic Paradoxes", "Language and Experience," "The Meaning of Counting," "Mathematical Systems," "The Axiomatic Method," "Pure and Applied Mathematics," and "The Significance of Incompleteness Theorems"; the last-mentioned paper is also quite difficult, but it constitutes not only one of the best semi-formal presentations of Gödel's theorems, but also helps make quite clear what their relevance is to considerations of the expressive power of formal languages in general. This collection constitutes a fine introduction to the philosophy of mathematics.—P. J. M. (shrink)

The author's central thesis is that a knowledge of set theory can be put to good use by the linguist interested in the syntax of natural languages. The author first points out the role of set theory in formal science, and then gives a short summary of some of the more important ideas. He then develops certain relations in set theory which are of special importance in the study of languages. A fair number of examples—admittedly in rather trivial form—which occur (...) in the study of language are exhibited to show some of the applications in mind. The last few pages are devoted to a review of how his thesis has fared. Although it may seem obvious to some that set theory is the means par excellence for the formal study of any discipline, many linguists apparently do not yet see this; this book will go some way toward demonstrating this.—P. J. M. (shrink)

Religion and the external world -- Projection, religion, and the external world -- The senses, reason and the imagination -- Realism, meaning and justification : the external world and religious belief -- Modality, projection and realism -- 'Our profound ignorance' : causal realism, and the failure to detect necessity -- Spreading the mind : projection, necessity and realism -- Into the labyrinth : persons, modality, and Hume's undoing -- Value, projection, and realism -- Gilding : projection, value and secondary qualities (...) -- The gold : good, evil, belief and desire -- The golden : relational values, realism and a moral sense. (shrink)

Natural duty theorists of political obligation try to base a moral duty to obey the law on some natural duty, such as the duty to promote justice. Their critics say they confront an insurmountable obstacle in the particularity problem: Since natural duties do not bind us to some persons and institutions more strongly than to others, they cannot support a duty to one particular state or society. I solve the particularity problem, by developing a version of the political obligation thesis, (...) giving a natural duty argument for it and showing that the particularity problem does not arise for the argument. I reply to some likely objections to my view. (shrink)

There have been two recent attempts to disentangle the evidence for the procedures in fourth-century Athens for the enactment and revision of nomoi, by D. M. MacDowell and by M. H. Hansen. I have learned from both, but think that further progress can be made. MacDowell distinguishes five separate measures: The Old Legislation Law, requiring action at a specified time, advance publicity for the new proposal, concurrent repeal of any existing law with which the new proposal conflicts, and a decision (...) by nomothetae who are omomokotes, men who have sworn the dicastic oath : this is described as a παλαις νόμος, and as the law καθ' ν σαν ο πρότεροι νομοθέαι. Replacing that c. 370, the New Legislation Law, no longer requiring action at a specified time, advance publicity, concurrent repeal, or that the nomothetae should be omomokotes: as a result of the change conflicting laws have been enacted, and for some time continuing to the mid 350s commissioners have had to be elected to sort out the conflicts. Still valid in the 350s, the Review Law, requiring an annual epicheirotonia of the laws in four subject divisions in the assembly on 11 Hecatombaeon , advance publicity for new proposals, and at the third assembly after 11 Hecatombaeon the appointment of nomothetae who are omomokotes to decide between the existing laws and the new proposals. (shrink)

The metaphysical problem of individuation requires an answer to two different but intimately related questions: 1) How are we to characterize individuality ontologically? To what ontological category or logical type does individuality belong? 2) What sort of distinction is there between the individuality and nature of an individual, e.g., a real distinction, a modal distinction, a distinction of reason, or some other distinction My purpose in this article is to clarify a bare particular account of individuation and respond to objections (...) that have been raised against bare particulars as individuators. (shrink)

It is the impression of neurologists who deal with cancer patients that the incidence of neurologic complications of cancer is increasing (Posner 1995). ...

The Greek polis has been arousing interest as a subject for study for a long time, but recent approaches have shown that it is a subject on which there are still important questions to be asked and worthwhile issues to be explored. This book contains a selection of essays which embody the results of the latest research. Beyond the historical development of the Greek polis , the contributors ask questions about the civic institutions of ancient Greece as a whole and (...) their relationships to each other. Questions of power or the significance of a written code of law are discussed as well as the nature of Greek overseas settlements. Development of the Greek Polis presents up-to-date research and asks up-to-date questions on various aspects of an important topic. (shrink)

A. R. W. Harrison in The Law of Athens, i , 63–5, argued that the exclusion of bastards from the phratries and the severe restriction of their right of inheritance does not entail their exclusion from Athenian citizenship; and that the form of Pericles' citizenship law, not stating that were to be , and Solon's law restricting the inheritance rights of , both point to the conclusion that bastards were not ipso facto debarred from citizenship. D. M. MacDowell in CQ (...) N.S. 26 , 88–91, rightly finds Harrison's positive arguments inconclusive, but suggests that three texts provide more definite support for this conclusion. (shrink)