Multigene delivery and expression systems are emerging as key technologies for many applications in contemporary biology. We have developed new methods for multigene delivery and expression in eukaryotic hosts for a variety of applications, including production of protein complexes for structural biology and drug development, provision of multicomponent protein biologics, and cell‐based assays. We implemented tandem recombineering to facilitate rapid generation of multicomponent gene expression constructs for efficient transformation of mammalian cells, resulting in homogenous cell populations. Analysis of multiple parameters (...) in living cells may require co‐expression of fluorescently tagged sensors simultaneously in a single cell, at defined and ideally controlled ratios. Our method enables such applications by overcoming currently limiting challenges.Here, we review recent multigene delivery and expression strategies and their exploitation in mammalian cells. We discuss applications in drug discovery assays, interaction studies, and biologics production, which may benefit in the future from our novel approach. (shrink)

The current rationale for Freedom of Speech is entangled in Enlightenment assumptions about the relationship of discourse to public life. This article critiques those assumptions and proposes an alternative rationale for Freedom of Speech based in assumptions of contemporary rhetorical theory.

The question concerning technology.--The turning.--The word of Nietzsche: "God is dead."--The age of the world picture.--Science and reflection.

Traditional mechanistic accounts of language processing derive almost entirely from the study of monologue. Yet, the most natural and basic form of language use is dialogue. As a result, these accounts may only offer limited theories of the mechanisms that underlie language processing in general. We propose a mechanistic account of dialogue, the interactive alignment account, and use it to derive a number of predictions about basic language processes. The account assumes that, in dialogue, the linguistic representations employed by the (...) interlocutors become aligned at many levels, as a result of a largely automatic process. This process greatly simplifies production and comprehension in dialogue. After considering the evidence for the interactive alignment model, we concentrate on three aspects of processing that follow from it. It makes use of a simple interactive inference mechanism, enables the development of local dialogue routines that greatly simplify language processing, and explains the origins of self-monitoring in production. We consider the need for a grammatical framework that is designed to deal with language in dialogue rather than monologue, and discuss a range of implications of the account. Key Words: common ground; dialogue; dialogue routines; language comprehension; language production; monitoring; perception-behavior link. (shrink)

Over the past three decades, the philosophy of biology has emerged from the shadow of the philosophy of physics to become a respectable and thriving philosophical subdiscipline. The authors take a fresh look at the life sciences and the philosophy of biology from a strictly realist and emergentist-naturalist perspective. They outline a unified and science-oriented philosophical framework that enables the clarification of many foundational and philosophical issues in biology. This book will be of interest both to life scientists and philosophers.

Algorithms silently structure our lives. Algorithms can determine whether someone is hired, promoted, offered a loan, or provided housing as well as determine which political ads and news articles consumers see. Yet, the responsibility for algorithms in these important decisions is not clear. This article identifies whether developers have a responsibility for their algorithms later in use, what those firms are responsible for, and the normative grounding for that responsibility. I conceptualize algorithms as value-laden, rather than neutral, in that algorithms (...) create moral consequences, reinforce or undercut ethical principles, and enable or diminish stakeholder rights and dignity. In addition, algorithms are an important actor in ethical decisions and influence the delegation of roles and responsibilities within these decisions. As such, firms should be responsible not only for the value-laden-ness of an algorithm but also for designing who-does-what within the algorithmic decision. As such, firms developing algorithms are accountable for designing how large a role individual will be permitted to take in the subsequent algorithmic decision. Counter to current arguments, I find that if an algorithm is designed to preclude individuals from taking responsibility within a decision, then the designer of the algorithm should be held accountable for the ethical implications of the algorithm in use. (shrink)

This is a reproduction of a book published before 1923. This book may have occasional imperfections such as missing or blurred pages, poor pictures, errant marks, etc. that were either part of the original artifact, or were introduced by the scanning process. We believe this work is culturally important, and despite the imperfections, have elected to bring it back into print as part of our continuing commitment to the preservation of printed works worldwide. We appreciate your understanding of the imperfections (...) in the preservation process, and hope you enjoy this valuable book. (shrink)

Do we directly perceive physical objects? What is the significance of the qualification ‘directly’ here? Austin famously denied that there was a unique interpretation by which we could make sense of the traditional debate in the philosophy of perception. I look here at Thompson Clarke’s discussion of G. E. Moore and surface perception to answer Austin’s scepticism.

We examine the unique nature of agency problems within publicly traded family firms by investigating the earnings management decision of dominant family owners relative to non-family. To do so, we draw upon literature demonstrating that family owners are loss averse with respect to the family’s socioemotional wealth, or the affective endowment derived from firm ownership and control. Our theory and findings suggest that potential reputational consequences of earnings management lead family principals to engage in less of this practice relative to (...) non-family firms, and that founder family firms are less likely than non-founder family firms to use earnings management. Moreover, the family-firm effect varies with the firm size, the degree of CEO entrenchment, and the firm’s stock structure. We provide important insights regarding differences between family and non-family principals in the use of unethical accounting practices, thereby extending agency theory and advancing an underdeveloped research area. (shrink)

The fundamental question whether, or in which sense, science informs us about the real world has pervaded the history of thought since antiquity. Is what science tells us about the world determined unambiguously by facts or does the content of any scientific theory in some way depend on the human condition? "Sokal`s hoax" added a new dimension to this controversial debate, which very quickly came to been known as "Science Wars". "Knowledge and the World" examines and reviews the broad range (...) of philosophical positions on this issue, stretching from realism to relativism, to expound the epistemic merits of science, and to address the central question: in which sense can science justifiably claim to provide a truthful portrait of reality? This book addresses everyone interested in the philosophy and history of science, and in particular in the interplay between the social and natural sciences. (shrink)

Euthanasia and physician-assisted suicide are common practice in the Netherlands. In response to increasing requests from patients to end their lives, physicians are finding themselves placed in particularly precarious situations because of advance directives written by patients suffering from severe dementia. In April 2020, the Supreme Court of the Netherlands issued two judgments in the so-called Dormicum case: a case involving the deliberate termination of the life of a 74-year-old woman suffering from advanced dementia by a geriatrician in a nursing (...) home in The Hague. The judgment of the lower criminal court was upheld, but the sanction imposed by the appellate disciplinary court was quashed. In this paper, the author reviews the two Supreme Court rulings, argues that both are fundamentally flawed and raises questions as to what they mean for Dutch criminal law, physicians, and patients going forward. (shrink)

Belief in Heaven is an essential part of the great monotheistic religions of Judaism, Christianity, and Islam. Famous theologians have written about it, and ordinary theists hope to go there after death. However, the concept of Heaven is neither clear nor unproblematic. There are three serious problems with the notion of Heaven. First, the concept of Heaven lacks coherence. Second, it is doubtful that theists can reconcile the heavenly character of Heaven with standard defenses against the argument from evil, such (...) as the free will defense. Finally, Heaven is unfair and thus in conflict with the goodness of God. -/- 1. Introduction -- 2. The Traditional Doctrine -- 3. The Coherence of Heaven -- 4. The Problem of the Heavenly Character of Heaven -- 5. The Unfairness of Heaven -- 6. Objections - 6.1 Objection 1 - 6.2 Objection 2 - 6.3 Objection 3 - 6.4 Objection 4 -- 7. Conclusion. (shrink)

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Fichte’s early review of C. A. L. Creuzer’s neglected and idiosyncratic skeptical book on free will posed a serious challenge to what at the time was emerging as a consensus Kantian position on the role of free choice in the generation of imputable action. Fichte’s review was directed as much against Reinhold’s important letter on freedom of the will as it was against Creuzer himself. In the course of his brief review, Fichte suggests an important recasting of the strategy of (...) the Kantian postulates of rational faith; he poses a dilemma for the Reinholdian understanding of the relationship among an autonomous practical will, a free power of choice, and the actions of natural human organisms; and he hints at a radical reappropriation of the rationalist doctrine of pre-established harmony in re-orienting the search for a defensible reconstruction of a broadly Kantian position on the problem of free will. (shrink)

Ageism is the view that it is of greater moral value to allocate health care resources to younger people than to older people. In medical ethics, it is well-known that standard interpretations of distributive principles such as utilitarianism and egalitarianism imply some form of ageism. At times, ethicists argue as if practical complications are the only or main reason for not abiding to ageism. In this article, we argue that inferences to ageism from such distributive principles tend to commit what (...) we call the anticipation-blindness fallacy: A much too narrow focus on life quality benefits of health care treatments inclines us to overlook the importance of life quality benefits of health care safety, that is the mere trust in and expectation of being treated and cared for as one grows old. This is a key omission because health safety has value for a much larger population and for much longer time. Taking health safety into account therefore has important implications as for how ageist we ought to be. (shrink)

This paper redirects some of the philosophical discussion of sexual objectification. Rather than contributing further to debates over what constitutes objectification and whether it is harmful, I argue that aesthetic experience is a useful tool for resisting objectification. Attending to our embodied experiences provides immediate evidence that we are subjects; aesthetically attending to that evidence is a way of valuing it. I consider the human body as an aesthetic site, then as an ethico-aesthetic site, and finally as a site of (...) resistance. In addition to deepening accounts of body aesthetic experience, this paper helps frame human bodies as integral to moral agency, rather than impediments to it. (shrink)

El artículo expone las limitaciones que el liberalismo de Nozick presenta para sancionar ciertas conductas omisivas. Los postulados de su obra «Anarquía, Estado y utopía» fundamentan una concepción negativa de la libertad y, en consecuencia, asientan los pilares de un «Estado mínimo» que protege a sus ciudadanos, esencialmente, contra las agresiones de terceros. De esta forma, el texto expone que dichos postulados permiten la imposición de prohibiciones, pero no tanto de obligaciones (normas de mandato o «normas de hacer»). Se vislumbra (...) de este modo que el liberalismo nozickiano adolece de obstáculos teóricos para sancionar algunas conductas omisivas que ocasionan o permiten peligros y resultados especialmente graves. (shrink)

Contrary to Mele's suggestion, not all garden-variety self-deception reduces to bias-generated false beliefs (usually held contrary to the evidence). Many cases center around self-deceiving intentions to avoid painful topics, escape unpleasant truths, seek comfortable attitudes, and evade self-acknowledgment. These intentions do not imply paradoxical projects or contradictory belief states.

Scientific discoveries are often to some degree influenced by luck. Whether luck’s influence is at odds with common-sense intuitions about responsibility, is the central concern of the philosophical debate about moral luck. Do scientists acknowledge that luck plays a role in their work and – if so – do they consider it morally problematic? The present article discusses the results of four focus groups with scientists, who were asked about their views on luck in their fields and its moral implications. (...) The participants underscored circumstantial luck as a key dimension of luck in science. Nevertheless, most participants insisted that there are ways of executing ‘control’ in science: They believe that virtues and skills can increase one’s chances for success. The cultivation of these skills and virtues was considered a reasonable ground for pride. Prizes and rewards were rarely tied to personal desert, but instead to their societal function. (shrink)

We reimplement the creature forcing construction used by Fischer et al. :1045–1103, 2017. https://doi.org/10.1007/S00153-017-0553-8. arXiv:1402.0367 [math.LO]) to separate Cichoń’s diagram into five cardinals as a countable support product. Using the fact that it is of countable support, we augment our construction by adding uncountably many additional cardinal characteristics, sometimes referred to as localisation cardinals.

Recent discussions of “German Idealism ” have laid new emphasis on its central concern with the self-determining or “unconditioned” status of self-consciousness, its critique of “reflective” or “foundationalist” epistemologies and metaphysics, and its account of “Reason” or conceptuality as immanent in all human experience and social life. This article contends that this revaluation throws new light upon Karl Marx’s 1841 doctoral dissertation on ancient Greek atomism. It argues that Marx’s interest in comparing the atomistic theories of Democritus and Epicurus lies (...) in their being historical species of reflective or “essentialist” thinking that attempts to identify an underlying “principle” behind or “beyond” sensible “appearance.” Epicurus is accorded praise by Marx on account of his clear awareness of the necessary contradiction at the heart of any such structure, and his oblique demonstration of its internal link with the individualism and alienation of the post-Hellenic world. Intimately related themes are then shown to animate the rhetorical declarations against religion, in the name of “Reason” and “Self-consciousness”, that frame the dissertation. The precise manner in which Marx formulates this opposition, it is argued, indicate a closer and more conscious affinity with the original project of post-Kantian Idealism than has hitherto been appreciated. While Marx is sure to have intended more than a simple recycling of this tradition, it is suggested that a greater sensitivity to its role in shaping his outlook will prove suggestive—if not conclusive—for thinking about where he means to take it. (shrink)

Re/reading the Past is concerned with the discourses of history, from the complementary perspectives of Critical Discourse Analysis (CDA) and Systemic Functional Linguistics (SFL). The papers in the book stress the discursive construction of the past, focussing on the different social narratives which compete for official acknowledgement. Issues of collective and cultural memory are addressed, reflecting the "linguistic turn" in the Social Sciences. The book covers a range of discourses, interpreting texts from popular culture to academic discourse including the construction (...) and evaluation of past events in a variety of places around the world. It is especially timely in its focus on the construction of time and value in a post-colonial world where history discourses are central to on-going processes of reconciliation, debates on war crimes, and the issues of amnesty and restitution. As such the book fills a significant gap in interdisciplinary debates as well as in register and genre analysis, and will be of general interest to historians, political scientists and discourse analysts as well as students and teachers of ESP (English for Specific Purposes) and EAP (English for Academic Purposes). (shrink)

The task of computing a function F with the help of an oracle X can be viewed as a search problem where the cost measure is the number of queries to X. We ask for the minimal number that can be achieved by a suitable choice of X and call this quantity the query complexity of F. This concept is suggested by earlier work of Beigel, Gasarch, Gill, and Owings on “Bounded query classes”. We introduce a fault tolerant version and (...) relate it with Ulam's game. For many natural classes of functions F we obtain tight upper and lower bounds on the query complexity of F. Previous results like the Nonspeedup Theorem and the Cardinality Theorem appear in a wider perspective. (shrink)

The historical consensus is that logical evidence is special. Whereas empirical evidence is used to support theories within both the natural and social sciences, logic answers solely to a priori evidence. Further, unlike other areas of research that rely upon a priori evidence, such as mathematics, logical evidence is basic. While we can assume the validity of certain inferences in order to establish truths within mathematics and test scientifi c theories, logicians cannot use results from mathematics or the empirical sciences (...) without seemingly begging the question. Appeals to rational intuition and analyticity in order to account for logical knowledge are symptomatic of these commitments to the apriority and basicness of logical evidence. This chapter argues that these historically prevalent accounts of logical evidence are mistaken, and that if we take logical practice seriously we fi nd that logical evidence is rather unexceptional, sharing many similarities to the types of evidence appealed to within other research areas. (shrink)

We investigate the behavior of cardinal characteristics of the reals under extensions that do not add new [Formula: see text]-sequences (for some regular [Formula: see text]). As an application, we show that consistently the following cardinal characteristics can be different: The (“independent”) characteristics in Cichoń’s diagram, plus [Formula: see text]. (So we get thirteen different values, including [Formula: see text] and continuum). We also give constructions to alternatively separate other MA-numbers (instead of [Formula: see text]), namely: MA for [Formula: see (...) text]-Knaster from MA for [Formula: see text]-Knaster; and MA for the union of all [Formula: see text]-Knaster forcings from MA for precaliber. (shrink)

We extend the construction of a global square sequence in extender models from Zeman [8] to a construction of coherent non-threadable sequences and give a characterization of stationary reflection at inaccessibles similar to Jensen’s characterization in L.