There are many layers of regulation governing DNA replication to ensure that genetic information is accurately transmitted from mother cell to daughter cell. While much of the control occurs at the level of origin selection and firing, less is known about how replication fork progression is controlled throughout the genome. In Drosophila polytene cells, specific regions of the genome become repressed for DNA replication, resulting in underreplication and decreased copy number. Importantly, underreplicated domains share properties with common fragile sites. The (...) Suppressor of Underreplication protein SUUR is essential for this repression. Recent work established that SUUR functions by directly inhibiting replication fork progression, raising several interesting questions as to how replication fork progression and stability can be modulated within targeted regions of the genome. Here we discuss potential mechanisms by which replication fork inhibition can be achieved and the consequences this has on genome stability and copy number control. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Applied Christian Ethics addresses selected themes in Christian social ethics. Part one shows the roots of contributors in the realist school; part two focuses on different levels of the significance of economics for social justice; and part three deals with both existential experience and government policy in war and peace issues.

Strange as it may seem today—especially given James’s reputation as a brilliant psychologist, an astute writer on religious life, and the eminent founder of pragmatism—no facet of James’s career received more ink in the general press than psychical research, at least during his lifetime.in his masterful introduction to Essays in Psychical Research, Robert McDermott observes that 1896 was a significant year for William James. He writes of James as a “weaver of intellectual and experiential threads” who “labored for the (...) removal of those ideas, beliefs, and habits of mind that block insight and imagination” and that, on this account, “[t]he year 1896 is instructive” . This paper attempts to shed .. (shrink)

Strange as it may seem today—especially given James’s reputation as a brilliant psychologist, an astute writer on religious life, and the eminent founder of pragmatism—no facet of James’s career received more ink in the general press than psychical research, at least during his lifetime.in his masterful introduction to Essays in Psychical Research, Robert McDermott observes that 1896 was a significant year for William James. He writes of James as a “weaver of intellectual and experiential threads” who “labored for the (...) removal of those ideas, beliefs, and habits of mind that block insight and imagination” and that, on this account, “[t]he year 1896 is instructive” (McDermott xxvii). This paper attempts to shed .. (shrink)

Although the two volumes of _Logic, Language, and Meaning_ can be used independently of one another, together they provide a comprehensive overview of modern logic as it is used as a tool in the analysis of natural language. Both volumes provide exercises and their solutions. Volume 1, _Introduction to Logic_, begins with a historical overview and then offers a thorough introduction to standard propositional and first-order predicate logic. It provides both a syntactic and a semantic approach to inference and validity, (...) and discusses their relationship. Although language and meaning receive special attention, this introduction is also accessible to those with a more general interest in logic. In addition, the volume contains a survey of such topics as definite descriptions, restricted quantification, second-order logic, and many-valued logic. The pragmatic approach to non-truthconditional and conventional implicatures are also discussed. Finally, the relation between logic and formal syntax is treated, and the notions of rewrite rule, automation, grammatical complexity, and language hierarchy are explained. (shrink)

Although the two volumes of _Logic, Language, and Meaning _can be used independently of one another, together they provide a comprehensive overview of modern logic as it is used as a tool in the analysis of natural language. Both volumes provide exercises and their solutions.

The central role played by Darwin's analogy between selection under domestication and that under nature has been adequately appreciated, but I have indicated how important the domesticated organisms also were to other elements of Darwin's theory of evolution-his recognition of “the constant principle of change,” for instance, of the imperfection of adaptation, and of the extent of variation in nature. The further development of his theory and its presentation to the public likewise hinged on frequent reference to domesticates.We have seen (...) that Darwin's reliance on the analogy between domesticated varieties and wild species was a bold and original step, in light of contemporary views on the nature of domesticates. However, as Darwin undoubtedly foresaw, his reliance on the analogy created difficulties as well as solving problems, and these began with his Malthusian codiscoverer of the principle of natural selection, Alfred Russel Wallace. Wallace's paper “On the Tendency of Varieties to Depart Indefinitely from the Original Type,” presented to the Linnean Scoiety along with the first public unveiling of Darwin's theory, states: We see, then, that no inferences as to varieties in a state of nature can be deduced from the observation of those occurring among domestic animals. The two are so much opposed to each other in every circumstance of their existence, that what applies to the one is almost sure not to apply to the other. Domestic animals are abnormal, irregular, artificial; they are subject to varieties which never occur and never can occur in a state of nature.62Much has been made of the similarity of views of Darwin and Wallace, but this quotation surely reveals how utterly different their views were on what to Darwin was an important matter. Several critics of the Origin saw Darwin's reliance on the domesticates as his Achilles heel. As Young has pointed out, Samuel Wilberforce included the following passage in his attack on the Origin: Nor must we pass over unnoticed the transference of the argument from the domesticated to the untamed animals. Assuming that man as the selector can do much in a limited time, Mr. Darwin argues that Nature, a more powerful, a more continuous power, working over vastly extended ranges of time, can do more. But why should Nature, so uniform and persistent in all her operations, tend in this instance to change? Why should she become a selector of varieties?63Another critic, Fleeming Jenkin, found the analogy a weakness in Darwin's theory because of the limited extent of variation in any one direction in domestic animals and plants.64 We have already seen that Darwin had confided a similar view to his notebook thirty years earlier, but changed his mind as a result of his profound study of domesticates. De Beer's reference to “an English country gentleman's knowledge of domestic plants and animals and their breeding”65 fails totally to recognize the originality and depth of Darwin's knowledge of domesticates.Why did Darwin, against the currents of his time, rely so heavily on mankind's experience with domesticated organisms to shape his theory about species in nature? On reason is that only with domesticates was an approach that came close to experimental verification possible. Darwin fully realized the inadequacies of the experiment, as is emphasized by his repeated contrasting of selection under nature and selection by man. Yet the extensive experience and data of plant and animal breeders offered the only reliable base against which Darwin could continually challenge his views. As he wrote in the introduction to Variation, with domestication, “man ... may be said to have been trying an experiment on a gigantic scale.”66 Given Darwin's high opinion of the quantitative work of Malthus and Quetelet (as emphasized by Schweber),67 and his unremitting efforts to secure data by which to test his theories, it was inevitable that he should attach high significance to domesticated varieties. John Tyndall, in his Belfast address of 1874, said: “The strength of the doctrine of Evolution consists, not in experimental demonstration (for the subject is hardly accessible to this mode of proof), but in its general harmony with scientific thought.”68 Darwin would have agreed with the latter thought, but I think he would have challenged the preceding one on the grounds that long experience with domesticated varieties did provide an element of experimental demonstration. It gave him confidence in his theory, and he used his vast knowledge of artificial selection boldly and creatively. (shrink)

This volume contains essays that examine infinity in early modern philosophy. The essays not only consider the ways that key figures viewed the concept. They also detail how these different beliefs about infinity influenced major philosophical systems throughout the era. These domains include mathematics, metaphysics, epistemology, ethics, science, and theology. Coverage begins with an introduction that outlines the overall importance of infinity to early modern philosophy. It then moves from a general background of infinity up through Kant. Readers will learn (...) about the place of infinity in the writings of key early modern thinkers. The contributors profile the work of Descartes, Spinoza, Leibniz, and Kant. Debates over infinity significantly influenced philosophical discussion regarding the human condition and the extent and limits of human knowledge. Questions about the infinity of space, for instance, helped lead to the introduction of a heliocentric solar system as well as the discovery of calculus. This volume offers readers an insightful look into all this and more. It provides a broad perspective that will help advance the present state of knowledge on this important but often overlooked topic. (shrink)

This study examines the frequency of consanguineous marriage and the coefficient of inbreeding in the United Arab Emirates. The study was conducted in Al Ain and Dubai cities between October 1994 and March 1995. A sample of 2033 married UAE females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high with a coefficient of (...) inbreeding of 0·0222. The commonest type of consanguineous marriage was between first cousins. Double first cousin marriages were common compared to other populations. The consanguinity rate in the UAE has increased from 39% to 50·5% in one generation. The level of consanguinity was higher in Al Ain than in Dubai. (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

In these evocative and elegiac writings L. T. C. Rolt meditates on landscape, history, poetry, steam railways, vintage cars and the endless summer days of his ...

Byzantine Empire; economic and social conditions; history.

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)