Graphical AbstractGene editing with engineered nucleases introduce double-strand breaks that are repaired by error-prone nonhomologous end-joining (NHEJ). In article number 1900126, Sara G. Trimidal et al. propose that the length and type or resulting indels can now be controlled by editing with different engineered nucleases or by manipulating the expression of NHEJ genes.

Genome editing with engineered nucleases (GEENs) introduce site‐specific DNA double‐strand breaks (DSBs) and repairs DSBs via nonhomologous end‐joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits (...) can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical‐ or alternative‐NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w. (shrink)

Ethical self-management; an introduction to systematic personality psychology, by M. C. Katz.--Four axiological proofs of the infinite value of man, by R. S. Hartman.--Some thoughts regarding the current philosophy of the behavioral sciences, by C. R. Rogers.--Autonomy and community, by D. Lee.--Synergy in the society and in the individual, by A. H. Maslow.--Human nature: its cause and effect; a theoretical framework for understanding human motivation, by M. C. Katz.--Mental health; a generic attitude, by G. W. Allport.--Love feelings in courtship couples; (...) an analysis, by R. P. Hattis.--Economic policies and human well-being, by W. A. Weisskopf.--The great transformation, by H. F. W. Perk.--Contingencies of reinforcement in the design of a culture, by B. F. Skinner.--For further reading. (shrink)

The application of ontology has thus far [in 1998] been confined almost exclusively to the field of knowledge representation. Ontology has been applied, for example, in the design of medical databases and in the construction of geographical information systems. One area which is naturally suited to ontological analysis is that of the law and of social institutions in general. -/- Legal systems are composed of legal entities, such as laws, contracts, obligations, and rights. Their application yields new categories of entities (...) such as: corporations, trademarks, marriages, and parcels of real estate. The categorization of these entities by different legal systems has not, by-and-large, been conducted in ways which exploit the tools of modern ontology. Consequently, contradictions and inconsistencies often arise in the law when, for instance, one type of entity is forced into two mutually exclusive categories (e.g., when software is considered both patentable and copyrightable). Papers are invited which consider these and related issues from a philosophical point of view. (shrink)

The central purpose of this paper is to sketch the logic of being a democrat. That is, what is involved in being a democrat will be defined and delineated. I shall proceed by first examining Richard Wollheim's alleged paradox of democratic theory. Wollheim's solution to the paradox will then be shown to be unsatisfactory. Next, the concept of being a democrat will be clarified. The stage will then be set for showing that Wollheim's alleged paradox of democratic theory dissolves upon (...) discerning what a democrat qua democrat is committed to believe. In the process of clarifying what is involved in being a democrat and dissolving the alleged paradox of democratic theory, it will become evident that one popular argument often levelled against resistance to democratic law is without foundation. This is the argument that any democrat who conscientiously disobeys valid democratic law is necessarily behaving inconsistently with his democratic principles; and, therefore, if someone does conscientiously disobey valid democratic law, it proves he is not ‘really’ a democrat after all. (shrink)

The central purpose of the paper is to elucidate the inalienable rights thesis, I.E. That there is at least one inalienable right. Various senses of 'natural right' and 'inalienable' are analyzed so as to further clarify what is or could be the meaning and the truth of that thesis. A widespread confusion between the meaning of the terms 'inalienable natural right' and 'indefeasible natural right' is dispelled. It is concluded that present thinking about inalienable natural rights does not reveal precisely (...) why and in what sense there is such a right. A successful defense of the inalienable rights thesis is suggested. (shrink)

The central purpose of this paper is to examine the case for political authority, i.e., the argument for having political authority rather than for having none. Thus, the case for political authority is the case against anarchism. My construction of that case owes much, no doubt, to observations made long ago by Thomas Hobbes and john locke. Nevertheless, these observations have never been stated in a satisfactory and systematic fashion, not even by Hobbes and locke themselves. Hobbes’ observations have, more (...) often than not, been misunderstood, and those of locke have generally been overlooked. However, this paper is not intended to be an exercise in the history of political philosophy. Rather, it is an assessment of a philosophical thesis, namely, that political authority is essential to man's survival and well-being. Although this thesis is rarely contested and, in fact, borders on the commonplace, it is contestable. Moreover, since disenchantment with authority and how it is exercised is growing, an examination of how men are likely to fare in its absence is appropriate. Such an examination is complex, but it is not impossible. (shrink)

This early work by Robin G. Collingwood was originally published in 1924 and we are now republishing it with a brand new introductory biography. 'Speculum Mentis' is an academic work on the subject of philosophy. Robin George Collingwood was born on 22nd February 1889, in Cartmel, England. He was the son of author, artist, and academic, W. G. Collingwood. He was greatly influenced by the Italian Idealists Croce, Gentile, and Guido de Ruggiero. Another important influence was his father, a professor (...) of fine art and a student of Ruskin. He published many works of philosophy, such as Speculum Mentis (1924), An Essay on Philosophic Method (1933), and An Essay on Metaphysics (1940). (shrink)

This book presents new results in computability theory, a branch of mathematical logic and computer science that has become increasingly relevant in recent years. The field's connections with disparate areas of mathematical logic and mathematics more generally have grown deeper, and now have a variety of applications in topology, group theory, and other subfields. This monograph establishes new directions in the field, blending classic results with modern research areas such as algorithmic randomness. The significance of the book lies not only (...) in the depth of the results contained therein, but also in the fact that the notions the authors introduce allow them to unify results from several subfields of computability theory. (shrink)

Informal construction -- Formal construction -- Limiting results.

The book deeply analyses the bilateral relations between Switzerland and the European Union and their effect on the former's sovereignty in the context of Europeanisation. This touches on philosophical debates on the complexity of sovereignty. What sovereignty is at stake when talking about Swiss-EU relations? This issue not only faces the elusiveness of sovereignty as a concept, but also the proliferation of hypocrisy on its presence within states. The book encounters the deconstructionist hypothesis stating that there is nothing to worry (...) about but the belief there is something to worry about. Derrida's deconstruction of sovereignty allows indeed one to grasp the fictional essence of sovereignty based on the metaphysics of presence. The presence of self-positing sovereign inches per secondeity is fictional since absent in the present, but spectrally present in the belief of its presence to come. Sovereignty is a matter of credibility, or the credible promise of a normative statement to come. Hence, the book challenges the realist/neorealist argument stating that states are credibly sovereign until proven otherwise and explains that the debate on state sovereignty calls for the unveiling of this hypocritical epistemology cunningly disguised as an objective presence. Swiss-EU relations thus become the cornerstone to not only theorise but also test sovereignty and deconstruct the two ontological and epistemological sides of the same coin, or the modern hypocrisy of sovereignty. This deconstruction constitutes the very problématique of any attempt to understand whether and how a state can be sovereign and solve the problem as to how to neutralise the différance and identify the difference between credible and incredible claims of sovereignty. This problématique connects the theory and practice of sovereignty innovatively, providing positivist evidence on the arguable credibility of the Swiss claim of sovereignty and confirming the presence of a theological dimension within politics.<. (shrink)

This treatise on aesthetics criticizes various psychological theories of art, offers new theories and interpretations, and draws important inferences concerning ...

This early work by Robin G. Collingwood was originally published in 1939 and we are now republishing it with a brand new introductory biography. 'An Autobiography' is the story of Collingwood's personal and academic life. Robin George Collingwood was born on 22nd February 1889, in Cartmel, England. He was the son of author, artist, and academic, W. G. Collingwood. He was greatly influenced by the Italian Idealists Croce, Gentile, and Guido de Ruggiero. Another important influence was his father, a professor (...) of fine art and a student of Ruskin. He published many works of philosophy, such as Speculum Mentis (1924), An Essay on Philosophic Method (1933), and An Essay on Metaphysics (1940). (shrink)

In the past ten years, there has been growing interest in and concern about protecting the privacy of personal medical information. Insofar as medical records increasingly are stored electronically, and electronic information can be shared easily and widely, there have been legislative efforts as well as scholarly analyses calling for greater privacy protections to ensure that patients can feel safe disclosing personal information to their health-care providers. At the same time, the volume of biomedical research conducted in this country continues (...) to grow. The budget of the National Institutes of Health, for example, was $20,298 million in 2001, having more than doubled from a budget of $9,218 million 10 years before. This growing body of research includes increased efforts to use stored medical records as a source of data for health services, epidemiologic, and clinical studies. (shrink)

W.K. Clifford’s famous 1876 essay The Ethics of Belief contains one of the most memorable lines in the history of philosophy: "it is wrong always, everywhere, and for anyone, to believe anything upon insufficient evidence." The challenge to religious belief stemming from this moralized version of evidentialism is still widely discussed today.

В эссе "О мнимом праве лгать из человеколюбия" И. Кант утверждает, что лгать абсолютно недопустимо даже в ситуациях, когда правдивость может угрожать благополучию третьего лица. Этот тезис, как и эссе Канта в целом.

In this volume Loader examines three substantial and historically important sets of documents the writings of Philo of Alexandria, the histories of Josephus, ...

In the past ten years, there has been growing interest in and concern about protecting the privacy of personal medical information. Insofar as medical records increasingly are stored electronically, and electronic information can be shared easily and widely, there have been legislative efforts as well as scholarly analyses calling for greater privacy protections to ensure that patients can feel safe disclosing personal information to their health-care providers. At the same time, the volume of biomedical research conducted in this country continues (...) to grow. The budget of the National Institutes of Health, for example, was $20,298 million in 2001, having more than doubled from a budget of $9,218 million 10 years before. This growing body of research includes increased efforts to use stored medical records as a source of data for health services, epidemiologic, and clinical studies. (shrink)

Ever since John Locke, philosophers have discussed the possibility of a normative epistemology: are there epistemic obligations binding the cognitive economy of belief and disbelief? Locke's influential answer was evidentialist: we have an epistemic obligation to believe in accordance with our evidence. In this dissertation, I place the contemporary literature on agency and reasons at the service of some such normative epistemology. I discuss the semantics of obligations, the connection between obligations and reasons to believe, the implausibility of Lockean evidentialism, (...) and some of the alleged connections between agency and justification. (shrink)