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)

A new critical approach to Jewish thinking and praxis, drawing upon key thinkers such as Adorno, Wittgenstein, Gdel, Heidegger and Celan.

The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Education should be a continuous process from birth to death. It is essentially a process leading to reconciliation of the human and divine elements in the constitution of a human being. Right relationship between God and man, spirit and matter, the whole and the part, should be a prime objective of educational techniques.

In this paper we introduce a new property of families of functions on the Baire space, called pseudo-dominating, and apply the properties of these families to the study of cardinal characteristics of the continuum. We show that the minimum cardinality of a pseudo-dominating family is min{.

The Restoration settlement, the political backcloth to Aubrey's essay, proceeded in two stages. The first, in, saw the rehabilitation of the King and the ...

Humans are an exceptionally cooperative species, but there is substantial variation in the extent of cooperation across societies. Understanding the sources of this variability may provide insights about the forces that sustain cooperation. We examined the ontogeny of prosocial behavior by studying 326 children 3–14 y of age and 120 adults from six societies (age distributions varied across societies). These six societies span a wide range of extant human variation in culture, geography, and subsistence strategies, including foragers, herders, horticulturalists, and (...) urban dwellers across the Americas, Oceania, and Africa. When delivering benefits to others was personally costly, rates of prosocial behavior dropped across all six societies as children approached middle childhood and then rates of prosociality diverged as children tracked toward the behavior of adults in their own societies. When prosocial acts did not require personal sacrifice, prosocial responses increased steadily as children matured with little variation in behavior across societies. Our results are consistent with theories emphasizing the importance of acquired cultural norms in shaping costly forms of cooperation and creating cross-cultural diversity. (shrink)

If the argument of this short study is sound, we have here a point of view which needs to be borne in mind as an aid to the solution of, not only textual and literary problems, but even more those problems which are associated with the attempt to employ such terms as 'polytheism' and 'monotheism' in connexion with Israelite thought, and also those which are inherent in the question of the prophetic psychology or, again, that of revelation. It may also (...) be argued that along this line we gain a new approach to the New Testament extension of Jewish Monotheism in the direction of the later Trinitarianism. . . . At any rate, we can see how it was possible for a Jewish Christian to relate his Messiah so closely with the divine Being as to afford a basis for the later (and Greek) metaphysical formulation of the doctrine of the Trinity. --from the author's conclusions. (shrink)

Author Aubrey Neal suggests that one of these issues that lingers with us today is scepticism, and in 'How Skeptics do Ethics', he unravels the thread of this philosophy from its origins in enlightenment thinking down to our present age.

An interdisciplinary and jurisprudential primer that seeks to ground students in basic concepts that undergird and influence legal reasoning and process. Presented in clear and compelling prose that efficiently plugs this common gap in baseline knowledge. Student-friendly orientation that synthesizes numerous books on individual topics to create a full-blown inquiry into various jurisprudential fields. An even-handed and efficient student guide that includes Theory and the Law; Law and Economics; Political Philosophy and Law; American Governmental Structure: Its Impact on Law; Law, (...) Dispute Resolution, and the Adversary System; and Historical, Jurisprudential, and Multidisciplinary Influences on Law. (shrink)

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not been (...) inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

Provision of education for children under five has recently become a political concern. At the same time, this relatively small field has been attracting increased research attention, with many early years practitioners seeking routes to initial and higher degrees. This book offers essential guidance for researchers and newcomers to the field, outlining opportunities in research as well as useful, sensitive and appropriate methods for researching childhood education.

This theoretical paper develops a conceptual framework that explains how companies can influence consumer behavior in terms of both social and business benefits through their corporate social marketing initiatives. Drawing from the source credibility literature, the article asserts that the effectiveness of CSM depends largely on the corporate credibility of a company in supporting a social cause. Based on this assertion, the framework identifies ten different antecedents of CSM credibility, which are organized into attributes of the company, attributes of the (...) CSM initiative, and attributes of the cause. Furthermore, this framework shows that CSM credibility affects the two examined consequences, intended prosocial behavior and consumer loyalty. Several research and managerial implications are developed based on the propositions specified in the framework. (shrink)

An accessible guide to the theories of 19 major educational thinkers, the strengths and limitations of their ideas, their relevance today and how they can be used in the classroom and other educational settings.

Provides an overview of a selection of the influential thinkers on education, whose writing has helped in shaping our views on teaching and learning.