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)

This collection by a distinguished group of philosophers, psychologists, and physiologists reflects an interdisciplinary approach to the central question of cognitive science: how do we model the mind? Among the topics explored are the relationships (theoretical, reductive, and explanatory) between philosophy, psychology, computer science, and physiology; what should be asked of models in science generally, and in cognitive science in particular; whether theoretical models must make essential reference to objects in the environment; whether there are human competences that are resistant, (...) in principle, to modelling; whether simulated thinking and intentionality are really thinking and intentionality; how semantics can be generated from syntactics; the meaning of the terms "representations" and "modelling;" whether the nature of the "hardware" matters; and whether computer models of humans are "dehumanizing." Contributors include Donald Davidson, Daniel C. Dennett, Margaret A. Boden, Adam Morton, Dennis Noble, T. Poggio, Colin Blakemore, K.V. Wilkes, P.N. Johnson-Laird, and Jonathan St. B.T. Evans. (shrink)

There has been plenty of empirical evidence which shows that the single-particle picture holds to a good approximation in atomic nuclei. In this picture, protons and neutrons move independently inside a mean-field potential generated by an interaction among the nucleons. This leads to the concept of nuclear shells, similar to the electronic shells in atoms. In particular, the magic numbers due to closures of the nucleonic shells, corresponding to noble gases in elements, have been known to play an important (...) role in nuclear physics. Here we propose a periodic table for atomic nuclei, in which the elements are arranged according to the known nucleonic shells. The nuclear periodic table clearly indicates that nuclei in the vicinity of the magic numbers can be understood in terms of a shell closure with one or two additional nucleons or nucleon holes, while nuclei far from the magic numbers are characterized by nuclear deformation. (shrink)

_The Lamp that Integrates the Practices_ is a systematic and comprehensive exposition of the most advanced yogas of the Esoteric Community Tantra as espoused by the Noble Tradition, an influential school of interpretation within the Mahayoga traditions of Indian Buddhist esoterism. Equal in authority to Nagarjuna's famous Five Stages, Aryadeva's work is perhaps the earliest prose example of the "stages of the mantra path" genre in Sanskrit. Its studied gradualism exerted immense influence on later Indian and Tibetan tradition, and (...) it is widely cited by masters from all four major lineages of Tibetan Buddhism. This volume presents the _Lamp_ in a tri-lingual format: its Sanskrit original critically-edited from recently-identified manuscripts, a critical edition of the eleventh-century Tibetan translation by Rin-chen Bzang-po, and a thoroughly-annotated English translation. Includes an introductory study discussing the history of the Guhyasamaja and its exegetical traditions, surveying the scriptural and commentarial sources of the Noble Tradition, and analyzing in detail the contents of the _Lamp_. Features a detailed, tri-lingual glossary. Published by American Institute of Buddhist Studies. (shrink)

Images of Native Americans and of aspects of Native American culture are common in advertisements in the United States. Three such images can be distinguished — the Noble Savage, the Civilizable Savage and the Bloodthirsty Savage images. The aim of this paper is to argue that the use of such images is not morally acceptable because these images depend upon an underlying conception of Native Americans that denies that they are human beings. By so doing, it also denies to (...) them any moral standing and thus any claim to moral consideration and treatment. I begin by arguing that the traits which are distinctively human are fostered only within a cultural framework consisting of the accumulated knowledge and activities of a group of human beings. I then argue that savages are conceptualized as natural and cultureless beings. Furthermore, within the traditional Western conceptualization of the world mere natural objects have no moral standing. Thus, it follows that Native Americans insofar as they are also merely natural objects would have no standing or status as moral beings. The conception of Native Americans as savages undercuts the very conditions for the possibility of moral respect. I then turn to an application of these principles to some current commercial uses of images of Native Americans and other indigenous peoples. (shrink)

In the quest for Buddhist reality, the inevitable comparison is made between it and the Brahmanic concept of supreme reality. In some quarters, it is alleged that both systems point at an identical nature of reality and maintain a similar method in arriving at it. After all, the historical Buddha was a Brahmin oriented in the Upaniṣadic tradition. He also engaged himself in the prevailing disciplinary practice of yoga to overcome the ill‐nature of the ordinary self (ātman) and like other (...) fellow Brahmins, he consummated his goal by immersing himself in the Supreme Self (Ātman/Brahman). Proponents go even further to identify this Supreme Self with the contents of Buddhist nirvāna and conclude rather facilely that Buddhism is nothing but an extension of Brahmanic thought. (shrink)

Samuel Johnson has an interesting comment on consequences and the telling of “white lies.” For example “Sick People and Children are often to be deceived for their Good.” David Hume apparently endorses this concept in one of his letters. Both Johnson and Rousseau anticipate Kant’s argument about consequences in that one is to tell the truth under all circumstances. Hume, I argue, would take issue with this claim in that there are cases that warrant telling white lies. Elsewhere he speaks (...) about “harmless liars” who indulge in “lying or fiction... in humorous stories.” And he says “Noble pride and spirit may openly display itself when one lies under calamity [defamation or slander] or opposition of any kind,” especially if the opposition puts one’s life in grave danger, so one’s self-preservation is threatened. Under situations like these, lying is justified. In regard to fiction, if lying is for the purpose of entertainment and where “truth is not of any importance,” it is permissible. These cases are discussed in some detail, and they offer, along with their analysis, a pragmatic defense of Hume’s position. (shrink)

Samuel Johnson has an interesting comment on consequences and the telling of “white lies.” For example “Sick People and Children are often to be deceived for their Good.” David Hume apparently endorses this concept in one of his letters. Both Johnson and Rousseau anticipate Kant’s argument about consequences in that one is to tell the truth under all circumstances. Hume, I argue, would take issue with this claim in that there are cases that warrant telling white lies. Elsewhere he speaks (...) about “harmless liars” who indulge in “lying or fiction... in humorous stories.” And he says “Noble pride and spirit may openly display itself when one lies under calamity [defamation or slander] or opposition of any kind,” especially if the opposition puts one’s life in grave danger, so one’s self-preservation is threatened. Under situations like these, lying is justified. In regard to fiction, if lying is for the purpose of entertainment and where “truth is not of any importance,” it is permissible. These cases are discussed in some detail, and they offer, along with their analysis, a pragmatic defense of Hume’s position. (shrink)

During Advent we prayerfully consider how Jesus was born to save us from death through his incarnation, death, and resurrection. Remembering this in light of your own death can change your life. Mememto mori or "remember your death" is a phrase long associated with the practice of remembering the unpredictable and inevitable end of one's life. This book is the latest in a series of books by Sr. Theresa Alethia Noble, FSP, that explores the traditional Christian practice of meditation (...) on death in light of Christ. This book will help you to connsider the four Last Things: death, judgment, hell, and heaven in the context of Advent. -- Adapted from back cover. (shrink)

The Periodic Table has the column of the noble gas atoms (He, Ne, Ar, Kr, Xe, Rn) as one of its main pillars. Indeed the inert chemical nature of their closed shell structure is so striking that it is sometimes extended to all such structures. Is it true however that any closed shell, say a closed d-subshell will denote a lack of chemical activity? Take the noble metals for instance, so renowned for their catalytic capacity. Platinum has 10 (...) electrons in its valence shell which makes one of its excited states to be a closed 5d10–6s0 state. Surely this state would not be expected to be crucial to the catalytic activity of platinum, or would it? Or take palladium whose ground state is precisely the 4d10–5s0 state, should we expect that an isolated Pd atom at near zero-point temperature would attack a closed-shell hydrogen molecule efficiently? We shall here show that this is precisely the case; the closed-shell excited states of nickel and platinum are indeed crucial, through symmetry avoided crossings, for their reactivity. Other valuable catalysts as ruthenium depend on their excited states with maximal d-shell occupancy for their activity. The most notable confirmation of this new finding; that closed d-shells are vital to the catalytic activity of noble metals however, is the case of palladium whose closed-shell ground state is indeed capable of attacking hydrogen and hydrocarbon molecules even at temperatures well below 10 K as was predicted theoretically and immediately confirmed experimentally. (shrink)

What is Life? This is the question asked by Denis Noble in this very personal and at times deeply lyrical book. Noble is a renowned physiologist and systems biologist, and he argues that the genome is not life itself: to understand what life is, we must view it at a variety of different levels, all interacting with each other in a complex web. It is that emergent web, full of feedback between levels, from the gene to the wider (...) environment, that is life. (shrink)

The Modern Synthesis has dominated biology for 80 years. It was formulated in 1942, a decade before the major achievements of molecular biology, including the Double Helix and the Central Dogma. When first formulated in the 1950s these discoveries and concepts seemed initially to completely justify the central genetic assumptions of the Modern Synthesis. The Double Helix provided the basis for highly accurate DNA replication, while the Central Dogma was viewed as supporting the Weismann Barrier, so excluding the inheritance of (...) acquired characteristics. This article examines the language of the Modern Synthesis and reveals that it is based on four important misinterpretations of what molecular biology had shown, so forming the basis of the four Illusions: 1. Natural Selection; 2. The Weismann Barrier; 3. The Rejection of Darwin’s Gemmules; 4. The Central Dogma. A multi-level organisation view of biology avoids these illusions through the principle of biological relativity. Molecular biology does not therefore confirm the assumptions of the Modern Synthesis. (shrink)

What is Life? To answer this question, Denis Noble argues that we must look beyond the gene's eye view. For modern 'systems biology' considers life on a variety of levels, as an intricate web of feedback between gene, cell, organ, body, and environment. He shows how it is both a biologically rigorous and richly rewarding way of understanding life.

Festschrift volume to K. Ramakrishna Rao, Indian psychologist, philosopher and educationist; contributed articles.

In the last book of The Consolation of Philosophy, Boethius develops his solution to the problem of divine foreknowledge and free choice. Interpreters standardly hold that this problem and his solution to it presuppose causal indeterminism. In this paper, I argue that Boethius, following a Neoplatonist view found in Proclus, is a causal determinist and compatibilist and maintains that God’s providential knowledge ensures the occurrence of all the events he knows. This alternative interpretation offers a better fit with Boethius’s text (...) and its historical antecedents and provides resources to address the main criticisms of his solution. (shrink)

Constitutional and judicial law-making is increasingly beginning to find its reflection not only in the Anglo-Saxon, but also in the Romano-Germanic legal family. However, the prerequisites for the use of this legal instrument are different, which determines the relevance of conducting a comparative analysis regarding the provision of such a mechanism in the USA and Kazakhstan. The purpose of the research is to identify common and distinctive features in the process of implementation of constitutional and judicial law-making in countries belonging (...) to different legal systems. The article uses the methods of analysis, synthesis, comparison, deduction and generalization. As a result, the specificity of ensuring the mechanism of constitutional law-making in the USA was expressed, taking into account various forms of law-making activity. It has been established that the development of constitutional provisions in the United States takes place with the help of the constitutional doctrines of the Supreme Court of the United States, which provide for the introduction of amendments to constitutional provisions without a formal procedure. As a result of the study of the experience of Kazakhstan, it was established that special priority was given to the role of precedent, in particular, the decision of the Supreme Court of the Republic of Kazakhstan. This is explained by the integrative nature of the Romano-Germanic legal system, which allows effective development of national legislation as a whole and its provisions. The obtained results can be used during the professional training of judges in the Republic of Kazakhstan. (shrink)

K. Satchidananda Murty (1924-2011) was a vociferous writer and an iconoclast. This volume is a collection of his unpublished writings. It includes Murty's views on the Veda, its meaning, relevance, and study, and shows the significance of the Vedāntic vision to the modern world. Murty elucidates the basic tenets of Advaita Vedānta and expounds the Advaitic doctrine of the relationships between Brahman and God, Brahman and the individual self, as well as between God and the world. In his writings, Murty (...) contrasts empirical knowledge with transcendental wisdom and surveys the history of Indian science and scientific views in ancient times. The book also includes Murty's musings on the scholar Śankara's philosophy, authorship and religious life. An important contribution to Indian philosophy, the volume will be of great interest to scholars, teachers and students of Hindu philosophy, Vedāntic philosophy, Advaita Vedanta, comparative philosophy, religious studies, and South Asian studies. (shrink)