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)

This document presents the Bonn PRINTEGER Consensus Statement: Working with Research Integrity—Guidance for research performing organisations. The aim of the statement is to complement existing instruments by focusing specifically on institutional responsibilities for strengthening integrity. It takes into account the daily challenges and organisational contexts of most researchers. The statement intends to make research integrity challenges recognisable from the work-floor perspective, providing concrete advice on organisational measures to strengthen integrity. The statement, which was concluded February 7th 2018, provides guidance on (...) the following key issues: § 1. Providing information about research integrity§ 2. Providing education, training and mentoring§ 3. Strengthening a research integrity culture§ 4. Facilitating open dialogue§ 5. Wise incentive management§ 6. Implementing quality assurance procedures§ 7. Improving the work environment and work satisfaction§ 8. Increasing transparency of misconduct cases§ 9. Opening up research§ 10. Implementing safe and effective whistle-blowing channels§ 11. Protecting the alleged perpetrators§ 12. Establishing a research integrity committee and appointing an ombudsperson§ 13. Making explicit the applicable standards for research integrity. (shrink)

How ought you to evaluate your options if you’re uncertain about which axiology is true? One prominent response is Expected Moral Value Maximisation, the view that under axiological uncertainty, an option is better than another if and only if it has the greater expected moral value across axiologies. EMVM raises two fundamental questions. First, there’s a question about what it should even mean. In particular, it presupposes that we can compare moral value across axiologies. So to even understand EMVM, we (...) need to explain what it is for such comparisons to hold. Second, assuming that we understand it, there’s a question about whether EMVM is true. Since there are many plausible rivals, we need an argument to defend it. In this paper, I’ll introduce a representation theorem for axiological uncertainty to answer these two questions. Roughly, the theorem shows that if all our axiologies satisfy the von Neumann–Morgenstern axioms, and if the facts about which options are better than which in light of your uncertainty also satisfy these axioms as well as a Pareto condition, then these facts have a relevantly unique expected utility representation. If I’m right, this theorem at once affords us a compelling way to understand EMVM—and specifically intertheoretic comparisons—and a systematic argument for its truth. (shrink)

Organizations have neither a right to the vote nor a weighty right to life. We need not enfranchise Goldman Sachs. We should feel few scruples in dissolving Standard Oil. But they are not without rights altogether. We can owe it to them to keep our promises. We can owe them debts of gratitude. Thus, we can owe some things to organizations. But we cannot owe them everything we can owe to people. They seem to have a peculiar, fragmented moral status. (...) What explains this? Individualistic views explain this in terms of individualistic notions alone. Such notions don’t invoke any distinctive features of organizations. They just invoke the features of individual members of organizations. Collectivistic views, instead, explain this in terms of collective notions alone. Such notions don’t invoke the features of individual members of organizations. They just invoke the features of those organizations. We argue that neither approach works. Instead, one needs to synthesize the two approaches. Some individual interests, we think, are distinctively collective. We, as individuals, have a distinctive interest in playing a part in successful collective action. From this, so we argue, flows the apparently peculiar, fragmented moral status of organizations. (shrink)

Introduction Introducing Accessibility theory 0.1 On the role of context Utterances cannot be processed and interpreted on their own. ...

The normative mechanics of promising seem complex. The strength and content of promissory obligations, and the residual duties they entail upon being violated, have various prima facie surprising features. We give an account to explain these features. Promises have a point. The point of a promise to φ is a promise-independent reason to φ for the promisee’s sake. A promise turns this reason into a duty. This explains the mechanics of promises. And it grounds a nuanced picture of immoral promises, (...) an argument against promissory bare wrongings, and a constraint on theories of why we have promissory obligations at all. (shrink)

Our private perception of listening to an individualized playlist during a jog is very different from the interaction we might experience at a live concert. We do realize that music is not necessarily a performing art, such as dancing or theater, while our demands regarding musical performances are conflicting: We expect perfect sound quality and the thrill of the immediate. We want the artist to overwhelm us with her virtuosity and we want her to struggle, just like a human. We (...) want to engage with the musical expression and rely on visual and physical cues. Considering that the ears of today's listeners are used to technologically mediated music, in this paper I explore the unique qualities of musical live performances and examine if our conception allows for new mechatronic inventions, in particular robotic musicians, to participate in this art form. Some of Godlovitch's main thoughts expounded in his work on "musical performance" [11] serve as a reference and starting point for this investigation. His concept of `personalism', which deprives computer-/program-based musical performances from expressive potential and creative accomplishment is an issue that I want to challenge by pointing out new approaches arising from a reective discourse on technology, embodiment and expression. The enquiry conducted illustrates, how in reasoning about machine performers and algorithmic realization of music, we also examine the perceptual, physical and social aspects of human musicianship, reconceptualizing our understanding of a musical live performance. (shrink)

The standard view of ignorance is that it consists in the mere lack of knowledge or true belief. Duncan Pritchard has recently argued, against the standard view, that ignorance is the lack of knowledge/true belief that is due to an improper inquiry. I shall call, Pritchard’s alternative account the Normative Account. The purpose of this article is to strengthen the Normative Account by providing an independent vargument supporting it.

The identity of indiscernibles states that indiscernible objects must be identical. Many philosophers have held that the PII turns out to be either true but trivial, or non-trivial but false, depending on how the notion of discernibility is spelled out. In this paper, I propose and defend an account of this notion which aims to yield a minimally non-trivial and yet plausible version of the PII. I argue moreover that this version of the principle is immune to a number of (...) well-known and recent objections to the PII. (shrink)

What role should the political ideal of non-domination play in theorizing global justice? The importance of this ideal is defended most prominently in neo-republican political thought where non-domination embodies a conception of political freedom and serves as the foundational ideal of state citizenship [Pettit, Philip. 1997. Republicanism: A Theory of Freedom and Government. Oxford: Clarendon Press; Laborde, Cecile. 2008. Critical Republicanism. Oxford, New York: Oxford University Press]. It has been argued, however, that these theories can be extended to the global (...) political community and yield a separate framework for global justice. This paper agrees with proponents of non-domination that there is a significant critical and normative potential in the ideal's capacity to speak to the structural inequalities of power in the global order and to make them central, in a way that not only encompasses but also moves beyond questions of redistribution. Yet it argues that this should be conceived as a complement to existing approaches to global justice, rather than a full-fledged alternative. Non-domination's central contribution lies in reframing our perspective on the political authority of states and global institutions. As such it should be viewed as a freestanding principle to assess the political legitimacy of institutionalized global power relations. (shrink)

_In _Diverse Families, Desirable Schools_, Mira Debs offers a richly detailed study of public Montessori schools, which make up the largest group of progressive schools in the public sector._ As public Montessori schools expand rapidly as alternatives to traditional public schools, the story of these schools, Debs points out, is a microcosm of the broader conflicts around public school choice. Drawing on historical research, interviews with public Montessori educators, and ethnographic case studies, Debs explores the forces that pull intentionally (...) diverse, progressive schools toward elitism. At the heart of Debs’s book is a thoughtful analysis of the notion of “fit” between parents and schools—an idea that is central to school choice, which is often marketed as an opportunity for parents to find the perfect fit for their kids. By exploring parents’ varied motivations in choosing these schools and observing how families experience—or fail to experience—a “good fit” _after_ having chosen a particular school, Debs makes an original contribution to the literature on school choice and sheds light on the dilemmas entailed in maintaining diversity in progressive charter and magnet schools. (shrink)

This study investigates switching costs in landmark-based wayfinding using olfactory and visual landmark information. It has already been demonstrated that there seem to be no switching costs, in terms of correct route decisions, when switching between acoustically and visually presented landmarks. Olfaction, on the other hand, is not extensively focused on in landmark-based wayfinding thus far, especially with respect to modality switching. The goal of this work is to empirically test and compare visual and olfactory landmark information with regard to (...) their suitability for wayfinding including a modality switch. To investigate this, an experiment within a virtual environment was conducted in which participants were walked along a virtual route of 12 intersections. At each intersection, landmark information together with directional information was presented, which was to be memorized and recalled in the following phase, either in the same or in the other modality. The results of the study show that, in contrast to the no-switching costs between auditory and visual landmarks in previous studies, switching costs occur when switching modality from visual to olfactory and vice versa. This is indicated by both longer decision times and fewer correct decisions. This means that a modality switch involving olfactory landmark information is possible but could lead to poorer performance. Therefore, olfaction may still be valuable for landmark-based-wayfinding. We argue that the poorer performance in the switching-condition is possibly due to higher cognitive load and the separate initial processing of odors and images in different cognitive systems. (shrink)

In his works for a few decades since the 1960s, Theodore Roszak, professor of California State University, has made an emphatic call to rethink all the fundamental objectives and values of the techno-scientific civilization and consumer society. His name became famous when he published his book “The Making of a Counterculture. Reflections on the Technotronic Society and Its Youthful Opposition” (New York, 1968), supporting the oppositional movement of the young Americans which he named counterculture. Theodore Roszak came to the conclusion (...) that the consumer society did not bring happiness to all people, that it could rapidly bring mankind to an environmental disaster, and that it is a blind alley in terms of social development. (shrink)

Replacements for corporate farm managers are increasingly hard to find. At the same time, there is a large pool of potential managers that has been hardly tapped into: young female professionals. Focusing on the supply side of the labor market for farm managers, we investigate how gender-specific life aspirations impact occupational intention. To explain gender-specific occupational intention, we operationalize two conceptual frameworks: a behavioral economic conceptualization that focuses on the material and non-material cost and benefits associated with occupational choice, and (...) a psychological conceptualization based on the theory of planned behavior. Our analysis of survey data among agricultural students shows that participating women are less inclined to pursue a farm manager position than participating men for two main reasons: first, they expect less internal benefits from such a position. Second, they believe to be less suited to meet the professional requirements. (shrink)

This paper discusses the volenti non fit injuria maxim. The volenti maxim states that a person is not wronged by that to which she consents, provided her consent is valid. I will argue, however, that the volenti maxim does not apply to all instances of valid consent. In some cases the consenter is wronged even if his consent is valid. Valid consent can only release others from consent-sensitive duties, not from consent-insensitive duties. If the consentee flouts a consent-insensitive duty the (...) consentee wrongs the consenter and thereby commits a wrong. (shrink)

La fraternidad nace en la experiencia sensible y se eleva luego a concepto racional. Radica ahí la dificultad de la aprehensión de su doble naturaleza, así como su eficacia política. Próxima a conceptos como amistad cívica, solidaridad o humanismo, se diferencia de todos ellos. Al analizar la fraternidad tal y como emerge a lo largo de la Revolución francesa a través de distintos autores en un contexto histórico político bien particular de crisis económica que se transmuta en revolución y cambio, (...) llegamos a la conclusión de que la fraternidad es una fuerza de acción colectiva que emerge en ese impás entre lo individual y lo colectivo que hace necesaria una restructuración del orden económico y político establecido. Por consiguiente, si aceptamos que el ser humano es un ser político, la fraternidad nos revela algo de la real naturaleza política, entendida más allá del simple pacto social, a saber: cuando el ser humano se apodera de la palabra, dirigida siempre al otro, conjugándola con la acción. (shrink)

Thus Plotinus (what is his status in the history of metaphysics and in the "Platonic" era, if one follows Heidegger's reading?), who speaks of presence, that is, also of morphē, as the trace of nonpresence, as the amorphous (to gar ikhnos tou amorphous morphē). A trace which is neither absence nor presence, nor, in whatever modality, a secondary modality.In his reading of Heidegger in his 2003 seminar, published as The Beast and the Sovereign, Derrida is particularly troubled by one particular (...) aspect of Heidegger: Heidegger's "superabundant use" of the language of Walten.1 "As you see," Derrida writes of Heidegger's use of Walten, "late in my life of reading Heidegger, I have just discovered a word that seems to .. (shrink)

“Postnatal depression” denotes the syndrome of dysphoria, debility, and anxiety that follows childbirth in about 10–20% of women (as variously estimated). Its etiology is seen to be lodged in a variety of psychosocial as well as biological factors, among which the isolating and pressured culture of contemporary society (especially for women/mothers) is commonly singled out as a powerful precipitator. This view is extended here through the evolutionary perspective which casts maternal distress as a set of adaptive responses with the function, (...) in ancestral environments, of soliciting support for a mother who feels that her maternal responsiveness may be threatened. As continuous caretaking of the infant is the active expression of evolved maternal responsiveness, departures from this pattern result in anxiety and distress that seek resolution. Manifestations of maternal distress in contemporary society are dysfunctional, however, since the present social structure does not provide spontaneous and immediate support that can spring forth within small, closely knit social units. Furthermore, for present-day mothers distress is self-perpetuating since the ingrained tendency toward continuing responsiveness rarely finds practical expression and is thus converted into anxious vigilance and depression. This view generates the hypothesis that the emotional and cognitive contents of maternal vigilance are associated with the needs of the infant and will therefore be focused on crying and feeding. A number of qualitative studies of women’s experiences during the postpartum bear out this prediction and support the feasibility of the evolutionary hypothesis of “postnatal depression” as a set of adaptive responses, now out of place in a novel environment. (shrink)

Most students step into our classrooms completely innocent of the notion of consciousness, consciousness studies, or the possibility of altering states of consciousness. Our task is to build our courses to meet these students needs at the undergraduate level, and to bring them slowly—and with care—into the realm of consciousness studies. Protection of human subjects surely extends to our students in the classroom and not just to natives of some distant or proverbial "bush.” There are, however, innumerable ways of doing (...) just this—consciousness studies with attention to the wide range of student experience—in any of our courses and at any level of instruction, and with awareness that perhaps the most interesting study of consciousness takes place through the alchemy of teaching—right there in the midst of our own classroom. (shrink)

The literature on sado‐masochism (S/M) and dominance and submission (D/S) tends to focus either on the psychodynamics of perversion or, in more magnanimous moments, on rites of reversal in the power relations of participants. This paper shifts the focus of analysis to the altered states of consciousness achieved in consensual S/M, bondage and fetish play and demonstrates the self‐conscious affinity between S/M and ecstatic religious practices like those well documented in the anthropological literature. The paper will explore sensory and other (...) shifts used to produce what one informant called "that transformative experience." It is posited that "dominance/ submission" and "top/bottom" are not simply asymmetrical relations in terms of power relations, but that they evoke fundamentally different states of consciousness. Further, altered states in consensual bondage and fetish play differ significantly in hetero‐ and homosexual play. The reasons for this appear to have both historical and political implications which are explored briefly in the paper. (shrink)

ABSTRACT: BACKGROUND: The governments and citizens of the developed nations are increasingly called upon to contribute financially to health initiatives outside their borders. Although international development assistance for health has grown rapidly over the last two decades, austerity measures related to the 2008 and 2011 global financial crises may impact negatively on aid expenditures. The competition between national priorities and foreign aid commitments raises important ethical questions for donor nations. This paper aims to foster individual reflection and public debate on (...) donor responsibilities for global health. METHODS: We undertook a critical review of contemporary accounts of justice. We selected theories that: (i) articulate important and widely held moral intuitions; (ii) have had extensive impact on debates about global justice; (iii) represent diverse approaches to moral reasoning; and (iv) present distinct stances on the normative importance of national borders. Due to space limitations we limit the discussion to four frameworks. RESULTS: Consequentialist, relational, human rights, and social contract approaches were considered. Responsibilities to provide international assistance were seen as significant by all four theories and place limits on the scope of acceptable national autonomy. Among the range of potential aid foci, interventions for health enjoyed consistent prominence. The four theories concur that there are important ethical responsibilities to support initiatives to improve the health of the worst off worldwide, but offer different rationales for intervention and suggest different implicit limits on responsibilities. CONCLUSIONS: Despite significant theoretical disagreements, four influential accounts of justice offer important reasons to support many current initiatives to promote global health. Ethical argumentation can complement pragmatic reasons to support global health interventions and provide an important foundation to strengthen collective action. (shrink)

Despite ever‐increasing accumulation of genomic data, the fundamental question of how individual genes are switched on during development, lineage‐specification and differentiation is not fully answered. It is widely accepted that this involves the interaction between at least three fundamental regulatory elements: enhancers, promoters and insulators. Enhancers contain transcription factor binding sites which are bound by transcription factors (TFs) and co‐factors expressed during cell fate decisions and maintain imposed patterns of activation, at least in part, via their epigenetic modification. This information (...) is transferred from enhancers to their cognate promoters often by coming into close physical proximity to form a ‘transcriptional hub’ containing a high concentration of TFs and co‐factors. The mechanisms underlying these stages of transcriptional activation are not fully explained. This review focuses on how enhancers and promoters are activated during differentiation and how multiple enhancers work together to regulate gene expression. We illustrate the currently understood principles of how mammalian enhancers work and how they may be perturbed in enhanceropathies using expression of the α‐globin gene cluster during erythropoiesis, as a model. (shrink)

Since the late 1970s, disruptions and “failure” of maternal-infant bonding have been causally linked to postpartum depression. Part I of this paper examines the grounds for this connection while tracing the ramifications of bonding theory (Klaus and Kennell 1976) through obstetrics, pediatrics, and psychiatry, as well as in the (mis)representations of it in the popular media. This discussion resolves into a view of maternal attachment as a long-term development progressively established through intensive mother-infant interaction. The forms of this interaction are (...) phylogenetically determined, albeit culturally and personally mediated. Flowing from this premise, Part II of the paper casts postpartum depression as an adaptive response to threat (from whatever cause) to adequate mothering, and develops an argument for the evolutionary role of enacted social ties in the establishment of maternal responsiveness. (shrink)

For Maria Markus, a significant feature of ‘decency’ of a society is respect for the dignity of each person. Here I contemplate the notion of ‘respect’ in the light of Sennett’s (2004) inquiry into the role of respect in encounters between individuals and institutions. Underlying this question is the structure/ agency dynamic. As Markus points out, decent institutions do not necessarily presuppose decent individuals (and vice versa). Yet the separation of these entities is analytic; in life, they are intertwined and (...) the resulting fabric rarely loses its opacity under sociologists’ inquiring gaze. One task of this article is to consider Sennett’s approach to the problem. But methodology is not my primary concern. More important is Sennett’s investigation of the vicissitudes of respect in the context of sundry inequalities. With reference to Markus’s discussion of ‘decency’, this article elucidates Sennett’s views concerning the necessary conditions for the generation and maintenance of respect in the face of obstacles put in its way by both social arrangements and human nature. (shrink)