-
92960.885656
The majority of mammalian genome is transcribed to RNA transcripts, of which only a very small percentage code for proteins . As a result, thousands of RNAs that do not code for proteins are produced in cells, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). These noncoding RNAs exert regulatory functions in various physiological and pathological conditions . In addition, numerous noncoding RNAs are expressed in a tissue- and cell-specific manner . Thus, a reporter that faithfully reflects the expression or activity of noncoding regulators of noncoding RNAs, but also for tracking cell fate and disease status. Previously we have designed a miRNA inducible CRISPR-Cas9 platform that can serve as a sensor for miRNA activities . However, designing a reporter for long noncoding RNAs has not been easy due to its untranslatable nature and low expression level. Here, we design an sgRNA precursor in an intron (GRIT) strategy that can monitor the promoter activity of lncRNAs (Fig. 1a). Furthermore, we show that GRIT can be used to track differentiation status of stem cells.
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92981.885845
We find, much to our surprise, that the percentage of mutation or duplication related to the early-onset Alzheimer’s disease (EOAD, the well-established hereditary disease) reported in the World Alzheimer’s Disease Report 2021 seems to fit a certain pattern. According to the report, PSEN1 mutation accounts for the majority of EOAD gene mutations (43%), frequency of APP mutation represents 16%, and those of PSEN2 and APOE4 mutations are 6% and 9.12%, respectively, with an average of 7.56%. The next level is the rare mutations in genes TREM2, SORLI , ABCA7 accounting for 1.17%, 1.42%, 1.33%, respectively1–3, with an average of 1.31%.
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268636.885859
In The Sources of Normativity, Korsgaard argues for what can be called “The Universality of Humanity Claim” (UHC), according to which valuing humanity in one’s own person entails valuing it in that of others. However, Korsgaard’s reliance on the claim that reasons are essentially public in her attempt to demonstrate the truth of UHC has been repeatedly criticized. I offer a sentimentalist defense, based on Adam Smith’s moral philosophy, of a qualified, albeit adequate, version of UHC. In particular, valuing my humanity, understood as (my awareness of) my perspective and the reasons determined from within it, entails valuing your humanity, understood as (your awareness of) your perspective and the reasons determined from within it. Given Korsgaard’s emphasis on the publicity of reasons in her argument for UHC, I also discuss the role of reasons in my account. I argue that the relative weights of at least some of an agent’s reasons are determined from within a shared evaluative point of view, namely, the standpoint of what Smith calls “the impartial spectator.” These reasons have normative authority over and constrain the agent’s private reasons, that is, those that are determined from within her own particular evaluative point of view.
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332533.88587
[Editor’s Note: The following new entry by Carl Knight
replaces the
former entry
on this topic by the previous author.]
If you believe that conduct in some case is right or wrong, you have a
moral judgment or intuition. Perhaps you have many such judgments
about different cases. You might, nevertheless, consider that
judgments alone do not justify the moral views they express. You and your moral interlocutors might be concerned that “what
we actually accept is fraught with idiosyncrasy and vulnerable to
vagaries of history and personality” (Elgin 1996: 108) or
displays “irregularities and distortions” (Rawls 1971:
48).
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395880.885883
Atomic and close-to-atomic scale manufacturing (ACSM) is the core competence of Manufacturing III. Unlike other conceptions or terminologies that only focus on the atomic level precision, ACSM defines a new realm of manufacturing where quantum mechanics plays the dominant role in the atom/molecule addition, migration and removal, considering the uncertainty principle and the discrete nature of particles. As ACSM is still in its infant stage, only little has been systematically elaborated at the core proposition of ACSM by now, hence there is a need to understand its concept and vision. This article elucidates the development of ACSM and clarifies its proposition, which aims to achieve a clearer understanding on ACSM and direct more effective efforts toward this promising area.
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426583.885895
For the many friends who’ve asked me to comment on the OpenAI drama: while there are many things I can’t say in public, I can say I feel relieved and happy that OpenAI still exists. This is simply because, when I think of what a world-leading AI effort could look like, many of the plausible alternatives strike me as much worse than OpenAI, a company full of thoughtful, earnest people who are at least asking the right questions about the ethics of their creations, and who—the real proof that they’re my kind of people—are racked with self-doubts (as the world has now spectacularly witnessed). …
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436456.885907
This is an English translation of the records of Lu Cheng (Lu Cheng lu 陸澄錄) in the first volume (juan shang 卷上) of the Record of Instructions for Practice (Chuan xi lu 傳習錄). Wang Yangming’s followers kept records of statements he made and conversations he held when discussing his Ruist learning with them. During and after his lifetime, these records were compiled in one or more volumes and titled Record of Instructions for Practice (or something similar). Many versions, each with different content, were published over the course of the sixteenth and seventeenth centuries. Some editions included a volume with a compilation of important correspondence and pedagogical writings. Among these, the three-juan version included in the
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436550.885917
In the first volume of Law, Legislation and Liberty (1973, Chaps. 1 and 2), F.A. Hayek exposes his famous criticism of the constructivist (or rationalist) approach to human history. As Hayek puts it, the latter approach assumes that humans are fully rational and thus can construct perfect social institutions because reason can advise them on how to impeccably do so. In this regard, Hayek (1973, Chap. 1, p. 12) writes: “Complete rationality of action in the Cartesian sense demands complete knowledge of all the relevant facts. A designer or engineer needs all the data and full power to control or manipulate them if he is to organize the material objects to produce the intended result. But the success of action in society depends on more particular facts than anyone can possibly know. And our whole civilization in consequences rests, and must rest, on our believing much that we cannot know [Hayek’s italics] to be true in the Cartesian sense.”
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481347.885927
Conflict over who belongs in womenonly spaces is now part of mainstream political debate. Some think womenonly spaces should exclude on the basis of sex, and others think they should exclude on the basis of a person’s selfdetermined gender identity. Many who take the latter view appear to believe that the only reason for taking the former view could be antipathy towards men who identify as women. In this paper, we’ll revisit the secondwave feminist literature on separatism, in order to uncover the reasons for womenonly spaces as feminists originally conceived them. Once these reasons are understood, those participating in debates over womenonly spaces will be in a better position to adjudicate on whether shifting from sex to gender identity puts any significant interests at stake.
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494269.885937
The alienation constraint on theories of well-being has been influentially expressed thus: ‘what is intrinsically valuable for a person must have a connection with what he would find in some degree compelling or attractive …. It would be an intolerably alienated conception of someone’s good to imagine that it might fail in any such way to engage him’ (Railton 1986: 9). Many agree this claim expresses something true, but there is little consensus on how exactly the constraint is to be understood. Here, I clarify the sense in which the quote offers a basic constraint on theories of well-being—a constraint that should be adopted by (e.g.) hedonists, desire satisfactionists, and objective list theorists alike. This constraint focuses on affective engagement, or positive affective stances in connection with a proposed good. I show that the constraint explains a near-universal intuition, and rules out a number of well-known theories of well-being.
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579195.885947
Two types of formal models—landscape search tasks and two-armed bandit models—are often used to study the effects that various social factors have on epistemic performance. I argue that they can be understood within a single framework. In this unified framework, I develop a model that may be used to understand the effects of functional and demographic diversity and their interaction. Using the unified model, I find that the benefit of demographic diversity is most pronounced in a functionally homogeneous group, and decreases with the increase of functional diversity.
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579257.885957
Philosophical analyses of the works of Jean-Paul Sartre usually focus on his theoretical writings, with his literary fiction treated as merely popularizing ideas whose full articulation can be found in those theoretical works. It is certainly true that Sartre wanted to use novels, plays, and films to bring his philosophy to a mass audience. But that is compatible with developing some ideas through those media. Indeed, his regular reliance on miniature stories to articulate and substantiate philosophical claims in his theoretical writings suggests that he found fiction especially conducive to this purpose. His strong emphasis on dialogue and character interaction in his plays and screenplays matches the formal structures of those vignettes in his theoretical works. Using drama in this way would allow him to develop an idea through a range of situations without being constrained by any theoretical formulation of that idea, while reaching a wider audience than would read his theoretical writings.
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603571.885979
In this short paper, I critically examine Veli Mitova’s proposal that social-identity groups can have collective epistemic reasons. My primary focus is the role of privileged access in her account of how collective reasons become epistemic reasons for social-identity groups. I argue that there is a potentially worrying structural asymmetry in her account of two different types of cases. More specifically, the mechanisms at play in cases of “doxastic reasons” seem fundamentally different from those at play in cases of “epistemic-conduct reasons.” The upshot is a need for further explanation of what unifies these dimensions of the account.
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677173.885989
In this article, we discuss epistemological limitations relating to the use of ethnoracial categories in biomedical research as devised by the Office of Management and Budget’s institutional guidelines. We argue that the obligation to use ethnoracial categories in genomics research should be abandoned. First, we outline how conceptual imprecision in the definition of ethnoracial categories can generate epistemic uncertainty in medical research and practice. Second, we focus on the use of ethnoracial categories in medical genetics, particularly genomics-based precision medicine, where ethnoracial identity is understood as a proxy for medically relevant differences among individuals. Notably, extensive criticisms have been made already against the genetic interpretation of races, but, nonetheless, the concept of race remains a key element of contemporary genomics. This motivates us to explore possible reasons why such criticisms may have been ineffective in redirecting attention to other (non-race-based) ways of controlling for human variability. We contend that popular arguments against the idea that human races have a genetic basis, though convincing in many respects, are not sufficient to exclude the pragmatic use of race and ethnicity as proxies for genetic variability related to complex phenotypes. Finally, we provide two further arguments to support the idea that ethnoracial categories are unlikely to provide meaningful insights into medical genetics, which implies that even the interpretation of race as a useful tool to stratify disease risk is unwarranted.
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719763.886004
There is an ethics of blaming the person who deserves blame. The Christian scriptures imply the following no-vengeance condition: a person should not vengefully overtly blame a wrongdoer even if she gives the wrongdoer the exact negative treatment that he deserves. I explicate and defend this novel condition and argue that it demands a revolution in our blaming practices. First, I explain the no-vengeance condition. Second, I argue that the no-vengeance condition is often violated. The most common species of blame involves anger; anger conceptually includes a desire for vengeance; and there are many pleasures in payback. Third, I clarify that it is possible to blame non-vengefully in anger and highlight three good uses for anger in non-vengeful blame. Fourth, I offer two reasons that justify the divine command prohibiting vengeance, and I note that the Christian God is merely sufficient to make non-vengeance morally obligatory. Fifth, I defend the no-vengeance condition against four biblical objections.
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725046.88602
This paper explores the potential of integrating ancient educational principles from diverse eastern cultures into modern AI ethics curricula. It draws on the rich educational traditions of ancient China, India, Arabia, Persia, Japan, Tibet, Mongolia, and Korea, highlighting their emphasis on philosophy, ethics, holistic development, and critical thinking. By examining these historical educational systems, the paper establishes a correlation with modern AI ethics principles, advocating for the inclusion of these ancient teachings in current AI development and education. The proposed integration aims to provide a comprehensive education that not only encompasses foundational knowledge but also advanced learning, thereby equipping future AI professionals with the necessary tools to develop AI systems that are ethically responsible, culturally aware, and aligned with human values such as fairness, safety, transparency, and collaboration. This approach not only addresses the AI alignment problem but also fosters cultural harmony and global understanding, which are crucial in an increasingly interconnected world. The paper posits that the wisdom of ancient educational systems, when harmonized with modern AI ethics, can guide the development of AI technologies that are beneficial for humanity, ensuring these advancements are not just technologically sound but also ethically and culturally informed.
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725081.886031
In his article Banicki proposes a universal model for all forms of philosophical therapy. He is guided by works of Martha Nussbaum, who in turn makes recourse to Aristotle. As compared to Nussbaum’s approach, Banicki’s model is more medical and less based on ethical argument. He mentions Foucault’s vision to apply the same theoretical analysis for the ailments of the body and the soul and to use the same kind of approach in treating and curing them. In his interpretation of philosophical therapy, there are, however, some controversial issues, to which we would like to call attention: Is restoring health by a philosophical method of treatment – health understood as a person’s ability to reach his/her vital goals – a convincing explication of philosophical therapy in general? In order to answer this question, it may be useful to look at Plato. It is not only Platonism (and especially Neo-platonism since Plotinus) that questions the idea that therapy is necessarily connected with „vital goals“. Buddhist and Gnostic philosophies are questioning „the vital“ in general. The immense effort in the history of philosophy to liberate the mind from the body casts doubt on the project to explain philosophical therapy solely in analogy to medical therapy.
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779454.886041
The phenomenon of interactive human kinds, namely kinds of people that undergo change in reaction to being studied or theorised about, matters not only for the reliability of scientific claims, but also for its wider, sometimes harmful effects at the group or societal level, such as contributing to negative stigmas or reinforcing existing inequalities. This paper focuses on the latter aspect of interactivity and argues that scientists studying interactive human kinds are responsible for foreseeing harmful effects of their research and for devising ways of mitigating them.
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883320.88605
With the release of GPT-3 and ChatGPT, large language models (LLMs) have been a hyped topic of international public and scientific debates. In this paper, we investigate the status of artificial systems in human-machine interactions by addressing the question of what we are doing when we interact with LLMs. Are we just playing with an interesting tool? Do we somehow enjoy a strange way of talking to ourselves? Or are we, in any sense, acting jointly with a collaborator when chatting with machines? Those questions lead us to the controversy about the classification of interactions with LLMs or other artificial systems. Assuming that current or future AI technology might contribute to the emergence of phenomena that can neither be classified as mere tool-use nor as proper social interactions, we explore conceptual frameworks that can characterize in-between phenomena. We discuss the pros and cons of ascribing some form of quasi-social agency to LLMs so they can at least participate in asymmetric joint actions.
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921200.886061
Introduction: Koro is a delusion whereby a man believes his penis is shrinking into his abdomen and this may result in his death. This socially-transmitted non-neuropsychological delusional belief occurs (in epidemic form) in South-East and South Asia. We investigated whether the two-factor theory of delusion could be applied to epidemic Koro.
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956222.886075
It is widely held that forgiveness is sometimes elective, such that prospective forgivers sometimes have discretion over whether (or at least, how soon) to forgive wrongdoers. It is also widely held that, in granting forgiveness, the forgiver changes the normative landscape connecting the forgiver and the forgiven; forgiveness is not only psychologically and socially significant, but normatively significant. Attention to the electivity and normativity of forgiveness, I argue, reveals our practices of forgiveness to be subject to a philosophically significant and unexplored form of moral luck. Rather than taking this kind of luck to count against the view that forgiveness is elective and normatively significant, I maintain that it contributes to an understanding of the ways in which we are morally vulnerable to those we culpably wrong. Furthermore, it provides a novel inroad for thinking about moral luck, moderately reconceived, more generally. For, assuming that there is an important way in which one’s being forgiven, upon apologizing, is determined by factors beyond one’s control—factors like the readiness or willingness of the victim to grant forgiveness—one might, given the normative significance of forgiveness, be morally lucky in being forgiven. But if the forgiven agent is morally lucky, assuming that this will not be a matter of her being less blameworthy than her unforgiven counterpart, we have available a view of moral luck that is non-trivial yet, in principle, adoptable by standard opponents of moral luck, those who reject that one’s blameworthiness can be determined (/intensified) by factors beyond one’s control that are causally downstream of one’s action.
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1071990.886084
Philosophers have started to theorize the concept of ‘affective injustice’ to make sense of certain ways in which people’s affective lives are significantly marked by injustice. This new research has offered important insights into people’s lived experiences under oppression. But it is not immediately clear how the concept ‘affective injustice’ picks out something different from the closely related phenomenon of ‘psychological oppression.’ This paper considers the question of why we might need new theories of affective injustice in light of the well-established cross-disciplinary literature on psychological oppression. I suggest that, whereas psychological oppression is found in the hearts and minds of people who are oppressed, affective injustice is most fruitfully understood as a structural phenomenon. It operates primarily outside of us: in affective norms, practices, and relationships that are embedded in social conditions of injustice. The account I offer is tentative and incomplete. But my hope is that it will help show how theorizing affective injustice has the potential to enrich existing theories of justice and theories of psychological oppression.
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1129425.886095
Assuring the well-being of children has emerged over the past several decades as an important goal for health and social policymakers. Although the concept of child well-being has been operationalized and measured in different ways by different child-serving entities, there are few unifying theories that could undergird and inform these various conceptual and measurement efforts. In this paper, we attempt to construct a theory of child well-being. We first review the social and policy history of the concept of child well-being, and briefly review its measurement based on these conceptualizations. We then examine three types of theories of well-being extant in philosophy – mental states theories, desire-based theories and needs-based theories – and investigate their suitability to serve as prototypes of a theory of child well-being. We develop a constraint that child well-being is important in and of itself and not merely as a way station to future adult well-being (we call this a non-reduction constraint). Using this constraint, we identify the limitations of each of the three sets of theories to serve as a basis for a theory of child well-being. Based on a developmentalist approach, we then articulate a theory of child well-being that contains two conditions. First, a child’s stage-appropriate capacities that equip her for successful adulthood, given her environment; and, second, an engagement with the world in child-appropriate ways. We conclude by reviewing seven implications of this theoretical approach for the measurement of child well-being.
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1184784.886113
In this paper, we introduce a distinctive kind of psychological abuse we call Tightlacing. We begin by presenting four examples and argue that there is a distinctive form of abuse in these examples that cannot be captured by our existing moral categories. We then outline our diagnosis of this distinctive form of abuse. Tightlacing consists in inducing a mistaken self-conception in others that licenses overburdening demands on them such that victims apply those demands to themselves. We discuss typical Tightlacing strategies and argue that Tightlacing typically is manipulative. Typical tightlacers will be motivated by a strong desire to suppress a kind of behaviour on the victim’s part. We will then differentiate Tightlacing from a related and widely discussed form of psychological abuse, Gaslighting. While Gaslighting focuses on the victim’s epistemic capacities and typically serves to insulate the abuser from potential dissent, Tightlacing focuses on the kind of person the victim is and typically serves to insulate the abuser from confronting ways of behaviour they cannot cope with. While Gaslighting targets the victim’s epistemic self-trust, Tightlacing targets their basic sense of who they are and their sense of entitlement to conduct themselves as who they really are. We finish by diagnosing the wrong-making features of Tightlacing, arguing that Tightlacing, among many secondary wrongs, makes the victim complicit in a denial of their rights as well as an erasure of who they are.
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1190943.886122
in order to discover what might explain and justify our concepts, ideas or practices ( Queloz 2021). It arguably originated with Hume, but its most prominent practitioners are Edward Craig and Bernard Williams.1 Each of these thinkers takes a target concept: property rights, knowledge and truthfulness respectively, and shows how the concept could have developed in the context of a heavily idealized human-like society, the so-called ‘state of nature’. Members of the society are portrayed as adopting the new concept because it solves an important problem for them. The second stage of this method involves noting the relevant structural similarities between our own society and the idealized model society: we use basically the same concept, we face basically the same problems. Then, the crucial inference arrives: given these similarities, we may conclude that we use the concept for basically the same reasons, and therefore that we have corresponding practical reasons to continue to do so. This is because we understand, in Craig’s words, “what the concept does for us, what its role in our life might be” (Craig 1990 2).
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1191055.886132
Much of the popular debate that surrounds no platforming centres on its putatively corrosive impact on free speech. This is apt to give a misleading picture of the particular puzzle that no platforming presents. Focusing on the university specifically, I contend that no platforming is distinctively objectionable not because it necessarily runs counter to general free speech values but when and because it is inconsistent with principles of academic freedom. This is because it conflicts with the status of members of the academy as those with the legitimacy to determine the appropriate bounds of free inquiry within the university. No platforming is objectionable insofar as it undercuts the authority of academic faculty in determining which speech, and by whom, is consistent with its purpose as an academic institution. Existing debates over no platforming have been too focused on which views are (or are not) given a platform and insufficiently attentive to the question of who decides who or what to platform. On the view defended here, no platforming by students is objectionable because, under principles of academic freedom, they should not be included in the constituency with the right to constrain the platforming of others.
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1191108.886142
Political liberals hold that the exercise of state power is legitimate only if it can be publicly justified—justified on the basis of public reasons. Many find this requirement too demanding and propose instead that there are just pro tanto reasons for laws and policies to be publicly justified. Here I argue that this alternative proposal fails to recognize that there are also distinct pro tanto reasons to have institutional requirements that laws and policies are publicly justified. This suggests an intermediate position between political liberals and their critics, which holds that states have reasons to adopt the kinds of institutions that political liberals favor—institutions that require public justification—but whether they should do so will depend on the costs and benefits of those institutions. This allows for a more practical approach to public justification by focusing on its application in particular political contexts.
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1191161.886151
Aesthetic evaluations of human bodies have important implications for moral recognition and for individuals’ access to social and material goods. Unfortunately, there is a widespread aesthetic disregard for non-white bodies. Aesthetic evaluations depend on the aesthetic properties we regard objects as having. And it is widely agreed that aesthetic properties are directly accessed in our experience of aesthetic objects. How, then, might we explain aesthetic evaluations that systematically favour features associated with white identity? Critical race philosophers, like Alia Al-Saji, Mariana Ortega, Paul C. Taylor, and George Yancy, argue that this is because the perception of racialized bodies is affected by the social structures in which they are appreciated. The aim of this paper is to propose how social structures can affect aesthetic perception. I argue that mental imagery acquired through the interaction with aesthetic phenomena structures the perception of non-aesthetic properties of bodies, so that aesthetic properties consistent with racist stereotypes are attributed to individuals.
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1191298.886161
There is an emerging consensus within Natural Law that explains transgender identity as an “embodied misunderstanding.” The basic line of argument is that our sexual identity as male or female refers to our possible reproductive roles of begetting or conceiving. Since these two possibilities are determined early on by the presence or absence of a Y chromosome, our sexual identity cannot be changed or reassigned. I develop an argument from analogy, comparing gender and language, to show that this consensus is premature. Language and gender imbue our body with further social meaning and so, I conclude, that just as we can learn multiple languages, so too can we learn multiple genders. Since language and gender each constitutively contribute to our wellbeing as a “second nature,” I argue against this consensus to show that the reason people who are transgender struggle to flourish is not because of a “troubled trans psyche,” but because there are conceptual, interpersonal, and institutional obstacles stacked against them.
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1191321.886172
In deciding whether to forgive, we often focus on the wrongdoer, looking for an apology or a change of ways. However, to fully consider whether to forgive, we need to expand our focus from the wrongdoer and their wrongdoing, and we need to consider who we are, what we care about, and what we want to care about. The difference between blame and forgiveness is, at bottom, a difference in priorities. When we blame, we prioritize the wrong, and when we forgive, we shift our priorities away from the wrong. Recognizing this essential role for priorities in forgiveness allows us to address a thorny puzzle in thinking about forgiveness: how is it that forgiveness can be both principled and elective? If there is sufficient reason to forgive, as will sometimes be the case because forgiveness is principled, how can it be reasonable to withhold forgiveness? Recognizing that forgiveness is a shift in our priorities dissolves this apparent tension between forgiveness being principled and forgiveness being elective.