Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released (...) DR9 and DR10 samples. Assuming a concordance Λ cold dark matter cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = at z = 0.32 and DV = at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = and H =. Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society. (shrink)

Hypotheses regarding the selective pressures driving the threefold increase in the size of the hominid brain since Homo habilis include climatic conditions, ecological demands, and social competition. We provide a multivariate analysis that enables the simultaneous assessment of variables representing each of these potential selective forces. Data were collated for latitude, prevalence of harmful parasites, mean annual temperature, and variation in annual temperature for the location of 175 hominid crania dating from 1.9 million to 10 thousand years ago. We also (...) included a proxy for population density and two indexes of paleoclimatic variability for the time at which each cranium was discovered. Results revealed independent contributions of population density, variation in paleoclimate, and temperature variation to the prediction of change in hominid cranial capacity (CC). Although the effects of paleoclimatic variability and temperature variation provide support for climatic hypotheses, the proxy for population density predicted more unique variance in CC than all other variables. The pattern suggests multiple pressures drove hominid brain evolution and that the core selective force was social competition. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and human (...) history. (shrink)

Originally published in 1913, this text was written in anticipation of the King's Speech for that year, which was due to include a Bill for the development of a National System of Education. The text puts forward the view that 'unless the Bill succeeds in making the most of the movement for reform springing from the schools themselves, it can but grant opportunities which will be incompletely utilised'. This book will be of value to anyone with an interest in the (...) history of education and educational reform. (shrink)

According to history texts, philosophers searched for a unifying natural law whereby natural phenomena and numbers are related. More than 2300 years ago, Aristotle postulated that nature requires minimum energy. More than 220 years ago, Euler applied the minimum energy postulate. More than 200 years ago, Lagrange provided a mathematical “proof” of the postulate for conservative systems. The resulting Principle of Least Action served only to derive the differential equations of motion of a conservative system. Then, 170 years ago, Hamilton (...) presented what he claimed to be a “general method in dynamics.” Hamilton's resulting “Law of Varying Action” was supposed to apply to both conservative and non-conservative systems and was supposed to yield either the differential equations of motion or the integrals of those differential equations. However, no direct evaluation of the integrals of motion ever resulted from Hamilton's law of varying action. In 1975, a scant 29 years ago, following five years of controversy with engineer mechanicians, Dr. Wolfgang Yourgrau, Editor, Foundations of Physics, published my first paper based on Aristotle's postulate, without mathematical proof. That and subsequent papers present, through applications, a true “general method in dynamics.” In this essay, I present the mathematical proof that is missing from my 1975 and subsequent papers. Six fundamental integrals of analytical mechanics are derived from Aristotle's postulate. First, however, Hamilton must be revisited to show why his H function and his “force function” prevents the law of varying action from being the general method in dynamics that he claimed it to be. I have found that Hamilton’s Law of Varying Action (HLVA), as Hamilton presented it, cannot be applied to systems for which the force function is non-integrable. In 1972, Dr. B.E. Gatewood and Dr. D.P. Beres (then a graduate student) discovered that the end-point term associated with the principle of least action does not vanish. I named the new equation, “the general energy equation.” In 1973, because I was doing with it what Hamilton claimed could be done with HLVA, I simply assumed that this new equation was HLVA. I gave the new equation the misnomer HLVA. In 2001, I learned that I had made a grave mistake. I found that HLVA is at most a special case of the general energy equation. My interpretation of Aristotle's postulate permits one to by-pass the differential equations of motion completely for both conservative and non-conservative systems (no calculus of variations). (shrink)

It is shown that, at the time of Euler and Lagrange, a belief led to an assumption. The assumption is applied to derive the principle of least action from the vis viva. The assumption is also applied to derive Hamilton's principles from the vis viva. It is shown that Hamilton, in his 1834 paper, countered the assumption of the earlier mathematicians. Finally, Hamilton's law, completely independent of the principle of least action and Hamilton's principles, is obtained to verify the foregoing (...) assertions. The unifying laws of classical mechanics, contained within Hamilton's 1834 paper, are identified. (shrink)

U.S. researchers and scholars often point to two legal factors as significant obstacles to the inclusion of pregnant women in clinical research: the Department of Health and Human Services’ regulatory limitations specific to pregnant women's research participation and the fear of liability for potential harm to children born following a pregnant woman's research participation. This article offers a more nuanced view of the potential legal complexities that can impede research with pregnant women than has previously been reflected in the literature. (...) It reveals new insights into the role of legal professionals throughout the research pathway, from product conception to market, and it highlights a variety of legal factors influencing decision-making that may slow or halt research involving pregnant women. Our conclusion is that closing the evidence gap created by the underrepresentation and exclusion of pregnant women in research will require targeted attention to the role of legal professionals and the legal factors that influence their decisions. (shrink)

Although psychologist impairment has received attention from researchers, there is a paucity of empirical data aimed at determining the point at which such impairment necessitates action. The purpose of this study was to provide such empirical data. Members of Division 42 ( n = 285) responded to vignettes describing a psychologist whose symptoms of either depression or substance abuse varied across five levels of severity. Results identified specific levels of impairment at which psychologists were deemed too impaired to practice psychotherapy, (...) as well as significant differences between ratings of increasingly severe impairment. Practical and ethical implications of these results are discussed. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

Intellectual contribution in the form of authorship is a fundamental component of the academic career. While research has addressed questionable and harmful authorship practices, there has largely been no discussion of how U.S. academic institutions interpret and potentially mitigate such practices through the use of institution-level authorship policies. To gain a better understanding of the role of U.S. academic institutions in authorship practices, we conducted a systematic review of publicly available authorship policies for U.S. doctoral institutions, focusing on components such (...) as specification of authorship criteria, recommendations for discussing authorship, dispute resolution processes, and guidance for faculty-student collaborations. We found that only 24% of the 266 Carnegie R1 and R2 Universities had publicly available authorship policies. Within these policies, the majority specified criteria for authorship, but provided less guidance about actual processes for applying such criteria, handling authorship disputes, and managing faculty-student author teams. Further, we found that any discussion of dispute resolution practices typically lacked specificity. Recommendations grounded in these findings are offered for institutions to leverage their ability to guide the authorship process by adopting an authorship policy that acknowledges disciplinary diversity while still offering substantive guidance. (shrink)

_Utilitarianism_ is a classic work of ethical theory, arguably the most persuasive and comprehensible presentation of this widely influential position. While he didn’t invent utilitarianism, John Stuart Mill offered its clearest expression and strongest defense, and he expanded the theory to account for the variety in quality that we find among pleasures and pains. The complete text of the 1871 edition is included, along with selections from Jeremy Bentham’s An Introduction to the Principles of Morals and Legislation. Andrew Bailey’s (...) detailed introduction examines the context of Mill’s writing and offers guidelines on how to read the text accurately and critically. The complete text of the 1871 edition of _Utilitarianism_ is presented here, with footnote annotations added to clarify unfamiliar references and terminology for the student reader. A detailed introduction by the editor is divided into brief digestible parts discussing the context of the text and offering guidelines on how to read it accurately and critically. This edition has its origin in the acclaimed _Broadview Anthology of Social and Political Thought_ and adheres to the anthology’s format and high standard of accuracy and accessibility. (shrink)

_Utilitarianism_ is a classic work of ethical theory, arguably the most persuasive and comprehensible presentation of this widely influential position. Mill argues that it is pleasure and pain that ought to guide our decision-making&and not the pleasure and pain of any one person or group, but the summative experience of all who are affected by our actions. While he didn’t invent utilitarianism, Mill offered its clearest expression and strongest defense, and expanded the theory to account for the variety in quality (...) that we find among specific pleasures and pains. Today, Mill’s version of the “Greatest Happiness Principle” is a standard premise in many moral arguments within the academy and in practical ethical and political deliberation. The complete text of the 1871 edition of _Utilitarianism_ is presented here, with footnote annotations added to clarify unfamiliar references and terminology for the student reader. A detailed introduction by the editor is divided into brief digestible parts discussing the context of the text and offering guidelines on how to read it accurately and critically. This edition has its origin in the acclaimed _Broadview Anthology of Social and Political Thought_ and adheres to the anthology’s format and high standard of accuracy and accessibility. (shrink)

Andrew Bailey's highly-regarded introductory anthology has been revised and updated in this new concise edition. First Philosophy: Knowing and Being brings together over thirty classic and contemporary readings in epistemology and metaphysics. Mindful of the intrinsic difficulty of the material, the editors provide comprehensive introductions both to each topic and to each individual selection. By presenting a detailed discussion of the historical and intellectual background to each piece, the editors enable readers to approach the material without unnecessary barriers to (...) understanding. A brief introduction to arguments is included, as are appendices on terminology and philosophical puzzles and paradoxes. (shrink)

_Utilitarianism_ is a classic work of ethical theory, arguably the most persuasive and comprehensible presentation of this widely influential position. Mill argues that it is pleasure and pain that ought to guide our decision-making&and not the pleasure and pain of any one person or group, but the summative experience of all who are affected by our actions. While he didn’t invent utilitarianism, Mill offered its clearest expression and strongest defense, and expanded the theory to account for the variety in quality (...) that we find among specific pleasures and pains. Today, Mill’s version of the “Greatest Happiness Principle” is a standard premise in many moral arguments within the academy and in practical ethical and political deliberation. The complete text of the 1871 edition of _Utilitarianism_ is presented here, with footnote annotations added to clarify unfamiliar references and terminology for the student reader. A detailed introduction by the editor is divided into brief digestible parts discussing the context of the text and offering guidelines on how to read it accurately and critically. This edition has its origin in the acclaimed _Broadview Anthology of Social and Political Thought_ and adheres to the anthology’s format and high standard of accuracy and accessibility. (shrink)

Alan Bailey offers a clear and vigorous exposition and defence of the philosophy of Sextus Empiricus, one of the most influential of ancient thinkers, the father of philosophical scepticism. The subsequent sceptical tradition in philosophy has not done justice to Sextus: his views stand up today as remarkably insightful, offering a fruitful way to approach issues of knowledge, understanding, belief, and rationality. Bailey's refreshing presentation of Sextus to a modern philosophical readership rescues scepticism from the sceptics.

Alan Bailey offers a clear exposition and defence of the philosophy of Sextus Empiricus, one of the most influential of ancient thinkers, the father of philosophical scepticism.

Alors que les phénoménologues prétendent avoir dépassé le solipsisme, la plupart n’ont en fait que repousser les frontières de l’intersubjectivité des individus humains aux individus des autres espèces. Pourtant, Husserl reconnaît l’existence d’une intersubjectivité interspécifique, c’est-à-dire d’une intersubjectivité dépassant les limites de l’espèce. Il va même jusqu’à affirmer qu’on comprend parfois mieux un animal familier qu’un humain étranger. Toutefois, même s’il admet que plusieurs animaux sont capables d’une vie de conscience subjective et qu’ils vivent dans un monde de sens partagé, (...) il ne les considère pas comme des « personnes » selon sa conception exigeante de la « personne » associée à la rationalité, à la maturité, la normalité et l’historicité. Reste qu’être une « personne », en son sens le plus primordial – et plus décisif puisque c’est celui sur lequel s’édifient des conceptions politiques,juridiques et éthiques – signifie simplement être le sujet d’un monde environnant, d’un monde commun et d’une existence biographique. Distinguer deux sens du concept de personne permet de reconnaître que les animaux ont part à la transcendantalité, qu’ils ne sont pas simplement en vie mais ont une vie à la fois biographique et communautaire, même s’ils ne sont pas en mesure de réfléchir à cette vie de conscience qui est la leur pour considérer leur place dans l’enchaînement des générations et pour adopter ce que Husserl appelle une « vocation ». La phénoménologie husserlienne des anomalies permet ainsi de reconnaître que les animaux ressortissent bien de la figure d’autrui, qu’ils sont des alter ego sujets d’une vie de conscience, et qu’à ce titre ils participent pleinement, comme les enfants, les fous et les étrangers, à la co-constitution du monde de l’esprit. (shrink)

ABSTRACTIs offering hazard pay ethically permissible when the pay premium is the only reason that a dangerous job is accepted? Robert C. Hughes argues that it is not. Central to his argument is the claim that in such cases, workers intend the foreseeable risks of harm as a means to the pay premium. Herein I question the plausibility of this claim and then develop a conception of the concept of means sufficient to make it plausible. By so doing, I provide (...) support for Hughes’s stringent position. (shrink)

Bailey, C. and R. Downey, Tabular degrees in \Ga-recursion theory, Annals of Pure and Applied Logic 55 205–236. We introduce several generalizations of the truth-table and weak-truth-table reducibilities to \Ga-recursion theory. A number of examples are given of theorems that lift from \Gw-recursion theory, and of theorems that do not. In particular it is shown that the regular sets theorem fails and that not all natural generalizations of wtt are the same.

A Significant distinction can be noticed in Cicero&s contemporary references to the anti-revolutionary parties in the first two Civil Wars. For both he claims superior dignitas: Rosc. Am. 136 quis enim erat qui non videret humilitatem cum dignitate de amplitudine contendere? , Lig. 19 principum dignitas erat paene par, non par fortasse eorum qui sequebantur. But in the Pro Roscio dignitas and nobilitas go together. Sulla's cause is causa nobilitatis , his party is the nobility , his triumph victoria nobilium (...) . Such expressions, frequent and casual, evidently belonged to current usage and may be assumed to have fitted the facts. Marian nobiles are indeed not lacking; but the records are meagre, and presumably they were a small minority in their class. An ironical hit at Verres tells the same tale ten years later: ut possit aliquis suspicari C. Verrem, quod ferre novos homines non potuerit, ad nobilitatem, hoc est adsuos transisse —for a nobilis, as such, Sulla was the only leader. Verres' true motive for changing sides, discreditable of course, is explained later on ; eo Sullanus repente foetus est, non ut honos et dignitas nobilitati restitueretur. (shrink)

A Significant distinction can be noticed in Cicero&s contemporary references to the anti-revolutionary parties in the first two Civil Wars. For both he claims superior dignitas: Rosc. Am. 136 quis enim erat qui non videret humilitatem cum dignitate de amplitudine contendere?, Lig. 19 principum dignitas erat paene par, non par fortasse eorum qui sequebantur. But in the Pro Roscio dignitas and nobilitas go together. Sulla's cause is causa nobilitatis, his party is the nobility, his triumph victoria nobilium. Such expressions, frequent (...) and casual, evidently belonged to current usage and may be assumed to have fitted the facts. Marian nobiles are indeed not lacking; but the records are meagre, and presumably they were a small minority in their class. An ironical hit at Verres tells the same tale ten years later: ut possit aliquis suspicari C. Verrem, quod ferre novos homines non potuerit, ad nobilitatem, hoc est adsuos transisse —for a nobilis, as such, Sulla was the only leader. Verres' true motive for changing sides, discreditable of course, is explained later on ; eo Sullanus repente foetus est, non ut honos et dignitas nobilitati restitueretur. (shrink)

Clonal expansion of T‐lymphocyte populations results from interactions of antigenic structures presented in combination with accessory cells (macrophages) and antibody recognition sites on the surface of T cells. The resulting activation of a membrane phospholipase C plays a crucial role in lymphocyte responses by releasing diglyceride and PIP3. The released diglyceride activates a cellular protein kinase C while PIP3 stimulates Ca2+ influx. Arachidonic acid released by the action of diglyceride lipase serves as substrate for the synthesis of bioactive eicosanoids (prostaglandins (...) and leukotrienes) which in turn modulate cellular adenyl and guanyl cyclases. The eicosanoids serve as both intra‐ and extra‐cellular signals for lymphocytes, regulating the production and expression of lymphokines and mediating the complex interactions between the monocyte‐macrophage components and helper and suppressor T cells.Aspirin and other anti‐inflammatory drugs stimulate mitogenesis by inhibiting production of the negative modulator prostaglandin E2 in accessory cells and by enhancing the production of the lymphokine 1L‐2 by producer T‐cells. (shrink)

Andrew Bailey's highly-regarded introductory anthology has been revised and updated in this new concise edition. First Philosophy : Knowing and Being brings together over thirty classic and contemporary readings in epistemology and metaphysics. Mindful of the intrinsic difficulty of the material, the editors provide comprehensive introductions both to each topic and to each individual selection. By presenting a detailed discussion of the historical and intellectual background to each piece, the editors enable readers to approach the material without unnecessary barriers (...) to understanding. A brief introduction to arguments is included, as are appendices on terminology and philosophical puzzles and paradoxes. (shrink)

Considered a foundational text in modern philosophy, the _Meditations on First Philosophy_ presents numerous powerful arguments that to this day influence debates in epistemology, the philosophy of mind, and the philosophy of religion. This new translation incorporates revisions from the second Latin edition and the later French translation to make Descartes’ reasoning as lucid and engaging as possible. Also included in this edition is a brief introduction to Descartes and the _Meditations_, revised and expanded from Andrew Bailey’s acclaimed anthology, (...) _First Philosophy_. The introduction helps the reader to understand the context and purpose of Descartes’ project without over-explaining his arguments. (shrink)

_First Philosophy: Knowing and Being_ brings together over thirty classic and contemporary readings in epistemology and metaphysics. Mindful of the intrinsic difficulty of the material, the editors provide comprehensive introductions both to each topic and to each individual selection. By presenting a detailed discussion of the historical and intellectual background to each piece, the editors enable readers to approach the material without unnecessary barriers to understanding. A brief introduction to arguments is included, as are appendices on terminology and philosophical puzzles (...) and paradoxes. (shrink)

The world of work over the past 3 years has been characterized by a great reset due to the COVID-19 pandemic, giving an even more central role to scholarly discussions of ethics and the future of work. Such discussions have the potential to inform whether, when, and which work is viewed and experienced as meaningful. Yet, thus far, debates concerning ethics, meaningful work, and the future of work have largely pursued separate trajectories. Not only is bridging these research spheres important (...) for the advancement of meaningful work as a field of study but doing so can potentially inform the organizations and societies of the future. In proposing this Special Issue, we were inspired to address these intersections, and we are grateful to have this platform for advancing an integrative conversation, together with the authors of the seven selected scholarly contributions. Each article in this issue takes a unique approach to addressing these topics, with some emphasizing ethics while others focus on the future aspects of meaningful work. Taken together, the papers indicate future research directions with regard to: (a) the meaning of meaningful work, (b) the future of meaningful work, and (c) how we can study the ethics of meaningful work in the future. We hope these insights will spark further relevant scholarly and practitioner conversations. (shrink)

Ludwig Wittgenstein (1889-1951) was an extraordinarily original thinker, whose influence on twentieth-century thinking far outside the bounds of philosophy alone. In this engaging Introduction, A.C. Grayling makes Wittgenstein's thought accessible to the general reader by explaining the nature and impact of Wittgenstein's views. He describes both his early and later philosophy, the differences and connections between them, and gives a fresh assessment of Wittgenstein's continuing influence on contemporary thought.

Philosopher Roger Scruton offers a wide-ranging perspective on philosophy, from logic to aesthetics, written in a lively and engaging way that is sure to stimulate debate. Rather than producing a survey of an academic discipline, Scruton reclaims philosophy for worldly concerns.