Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

Neuroethics entails investigations of neurocognitive mechanisms of morality and ethics; and studies and address of the ethical issues spawned by the use of neuroscience and its technologies to investigate cognition, emotion and actions. These two principal emphases, or what have been called “traditions” of neuroethics both mirror traditional bioethical discussions (such as debates about the safety of technological and pharmaceutical advances and ethical implications of new scientific and technological discoveries), and engage discourse about neuroscientific investigations of (proto-moral and moral) cognition, (...) emotions and behaviors, and what such findings may mean for human beliefs and conduct - from the individual to the political levels. (shrink)

BackgroundPublic Safety Personnel are routinely exposed to human suffering and need to make quick, morally challenging decisions. Such decisions can affect their psychological wellbeing. Participating in or observing an event or situation that conflicts with personal values can potentially lead to the development of moral injury. Common stressors associated with moral injury include betrayal, inability to prevent death or harm, and ethical dilemmas. Potentially psychologically traumatic event exposures and post-traumatic stress disorder can be comorbid with moral injury; however, moral injury (...) extends beyond fear to include spiritual, cognitive, emotional or existential struggles, which can produce feelings of severe shame, guilt, and anger.ObjectiveThis scoping review was designed to identify the extant empirical research regarding the construct of moral injury, its associated constructs, and how it relates to moral distress in firefighters, paramedics, and police officers.MethodsA systematic literature search of peer-reviewed research was conducted using databases MEDLINE, EMBASE, APA PsychInfo, CINHAL PLUS, Web of Science, SCOPUS, and Google Scholar. Included studies were selected based on the inclusion criteria before being manually extracted and independently screened by two reviewers.ResultsThe initial database search returned 777 articles, 506 of which remained after removal of duplicates. Following review of titles, abstracts, and full texts, 32 studies were included in the current review. Participants in the articles were primarily police officers, with fewer articles focusing on paramedics and firefighters. There were two studies that included mixed populations. Most studies were qualitative and focused on four topics: values, ethical decision-making, organizational betrayal, and spirituality.ConclusionPublic safety organizations appear to recognize the experience of moral distress or moral injury among public safety personnel that results from disconnects between personal core values, formal and informal organizational values, vocational duties, and expectations. Further research is needed to better understand moral distress or moral injury specific to public safety personnel and inform training and treatment in support of public safety personnel mental health. (shrink)

Paperwork plays a key role in a how institutions accommodate, refuse, or manage disabled people. This article develops modes for reading paperwork that build on each other, beginning with (a) recognizing the institutional pressures at work in shaping bureaucratic practices, then (b) considering how a person's relationship to disability influences how they might encounter these practices, and ultimately (c) noticing how the encounter between disabled/mad people and an institution might create something new, what the author calls archival excess. These methods (...) for reading are in conversation with disability studies, medical humanities, and document studies, and ultimately work toward a goal adapted from the principles of Disability Justice: recognizing the wholeness of disabled subjects in institutional archives. (shrink)

The boundaries, openness and character of the future European society will crucially depend on the degree and scope of identity politics. Religion, culture and nationality remain strong reference frameworks for individuals in their inter-personal but also political relations and tend, in practice, to favour weak rather than strong forms of citizenship. Whether this is a viable model for large and diverse democratic societies is an old debate known primarily from the discussions and theory on multiculturalism. How this debate is played (...) out at European level and especially with respect to the role of religion is illustrated with reference to the ideas of Daniel Cohn-Bendit and Tariq Ramadan, two well-known public figures with a strong commitment to Europe and European identity, albeit from rather different perspectives and outlooks. At the substantive or philosophical level, it appears impossible to resolve the fundamental questions underlying the opposition between liberalism and communitarianism as represented by the two men. The usefulness of a middle-range pragmatic approach insofar as political solutions or societal compromises are concerned is scrutinized for its usefulness. (shrink)

The lack of access to gender-affirming surgery represents a significant unmet health care need within the transgender community, frequently resulting in depression and self-destructive behavior. While some transgender people may have access to gender reassignment surgery, an overwhelming majority cannot afford facial feminization surgery. The former may be covered as a “medical necessity,” but FFS is considered “cosmetic” and excluded from insurance coverage. This demarcation between “necessity” and “cosmetic” in transgender health care based on specific body parts is in direct (...) opposition to the scientific community’s understanding of gender dysphoria and professional guidelines for transgender health. GRS affects one’s ability to function in an intimate relationship, while FFS has the same impact on social interactions an, therefore may have a far greater implication for one’s quality of life. FFS is a cost-effective intervention that needs to be covered by insurance policies. The benefits of such coverage far exceed the insignificant costs. (shrink)

This article, based on grandparents' narratives collected in a doctoral research project, aims to weave together reflections on childhood, intergenerational bonding, and love. Seven grandmothers and three grandfathers, between fifty-one and seventy-one years old, participated in the research; nine residents of the city of Rio de Janeiro and one of Niterói, Brazil. In addition, narratives were collected from six of their grandchildren, all of them between five and twelve years old, and residents of Rio de Janeiro, Niterói, Brasília and Montevideo, (...) Uruguay. Conducted during the Covid-19 pandemic, our methodological strategy involved interviews conducted on Zoom. Interviews with the adults were conducted individually, and collectively with the children. The themes that emerged in the grandparents' narratives led to reflections on the relationship between adults and children that are emblematic of the conception of childhood found in Walter Benjamin's work, as well as the philosophical anthropology of Martin Buber and the psychoanalysis of Donald Winnicott. The emphasis of the research participants was on affective security, built on the basis of small, everyday gestures, which result in an atmosphere of mutual support between children and adults. From these affectionate encounters between the youngest and the oldest, what we characterize as a “childlike force” is established—an energy field that produces new existential possibilities. The narratives collected here teach us new ways of being adult through our relationships with children: in our encounter with the lifeworlds of the youngest among us, we re-encounter our own deeper sensibilities, and regain the ability to play, to create, and to reinvent ourselves in relearning the joy of beginnings. (shrink)

The concept of yinyang lies at the heart of Chinese thought and culture. The relationship between these two opposing, yet mutually dependent, forces is symbolized in the familiar black and white symbol that has become an icon in popular culture across the world. The real significance of yinyang is, however, more complex and subtle. This brilliant and comprehensive analysis by one of the leading authorities in the field captures the richness and multiplicity of the meanings and applications of yinyang, including (...) its visual presentations. Through a vast range of historical and textual sources, the book examines the scope and role of yinyang, the philosophical significance of its various layers of meanings and its relation to numerous schools and traditions within Chinese philosophy. By putting yinyang on a secure and clear philosophical footing, the book roots the concept in the original Chinese idiom, distancing it from Western assumptions, frameworks and terms, yet also seeking to connect its analysis to shared cross-cultural philosophical concerns. (shrink)

Since its inception, modern anthropology has stood at the confluence of two mutually constitutive modes of knowledge production: participant-observation and theoretical analysis. This unique combination of practice and theory has been the subject of recurrent intellectual and methodological debate, raising questions that strike at the very heart of the discipline. How Do We Know? is a timely contribution to emerging debates that seek to understand this relationship through the theme of evidence. Incorporating a diverse selection of case studies ranging from (...) the Tibetan emotion of shame to films of Caribbean musicians, it critically addresses such questions as: What constitutes viable anthropological evidence? How does evidence generated through small-scale, intensive periods of participant-observation challenge or engender abstract theoretical models? Are certain types of evidence inherently better than others? How have recent interdisciplinary collaborations and technological innovations altered the shape of anthropological evidence? Extending a long-standing tradition of reflexivity within the discipline, the contributions to this volume are ethnographically-grounded and analytically ambitious meditations on the theme of evidence. Cumulatively, they challenge the boundaries of what anthropologists recognise and construct as evidence, while pointing to its thematic and conceptual potential in future anthropologies. (shrink)

王玉玺先生用隶、行两体书写“墨经”,内容包括:世界观;认识论;逻辑学;方法论;历史观;经济学等。.

The concept of a G‐quartet, a unique structural arrangement intrinsic to guanine‐rich DNA, was first introduced by Gellert and colleagues1 over 40 years ago. For decades, it has been uncertain whether the G‐quartet and the structure that it gives rise to, the G‐quadruplex, are purely in vitro phenomena. Nevertheless, the presence of signature G‐rich motifs in the eukaryotic genome, and the plethora of proteins that bind to, modify or resolve this nucleic acid structure in vitro have provided circumstantial evidence for (...) its physiological relevance. More recently, direct visualisation of G‐quadruplex DNA at native telomeres was achieved, bolstering the evidence for its existence in the cell. Furthermore, G‐quadruplex folded telomeric DNA has been found to perturb telomere function and to impede the action of telomerase, an enzyme overexpressed in >85% of human cancers, hence opening up a novel avenue for cancer therapy in the form of G‐quadruplex stabilising agents. BioEssays 29: 155–165, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The Arabic original of the ninth-century Kitāb al-Nawāmīs has not been discovered, save for three incomplete chapters. We have access to a fuller version only through a Latin translation, often known as the Liber vaccae, a title derived from its notorious experiments which involve the gruesome slaughter and mutilation of a cow to magically produce a rational animal or bees. Recent research on the Liber vaccae has focused mostly on its reception in medieval and early modern Europe. By contrast, the (...) present article explores the Indo-Arabic tradition to which Kitāb al-Nawāmīs belongs, as a re-orientation of the Liber vaccae established on two levels: textual and theoretical. Section I, on 'Texts and Practices', introduces ʿUyūn al-ḥaqāʾiq of Abū al-Qāsim al-ʿIrāqī, a text on magical practices which contains 26 chapters that correspond to sections in the Liber vaccae, affording us a glance into the Arabic reception of Kitāb al-Nawāmīs and bringing us closer to the Arabic original. The textual connection is established further by highlighting parallels between the experiments of the Liber vaccae / Kitāb al-Nawāmīs and other texts on natural magic, namely Ghāyat al-ḥakīm of Maslama al-Qurṭubī and Kitāb al-Sumūm by Ibn Waḥshiyya. Section II investigates the theoretical bases of the Liber vaccae / Kitāb al-Nawāmīs, by associating its content with the theories of spontaneous and artificial generation in Kitāb al-Tajmīʿ attributed to Jābir ibn Hayyān, Ghāyat al-ḥakīm, Kitāb al-Sumūm and, finally, another work by Ibn Waḥshiyya, al-Filāḥa al-nabaṭiyya. Jābir's and al-Qurṭubī's works have been studied in relation to the Liber vaccae by David Pingree, Maaike Van der Lugt, Sophie Page and William Newman; their findings are re-evaluated here in light of the texts of Ibn Waḥshiyya and al-ʿIrāqī. (shrink)

With the rise of the “humanitarian drone” in recent years, drones have become one of the most controversial public interest technologies that have gained increasing media attention. It is worth noting that, although there is a perception in the aid sector that drones hold the promise to reinvent the health supply logistics, to date, routine drone delivery is still relatively new and largely unproven. This paper presents a recent field study conducted in 2019, where drones were deployed in Malawi to (...) help address the last mile challenge in medical supply delivery, and where a noticeable mentality of “killing two birds with one stone” around the attempt of using drones in resource-poor settings is observed. The objective of the paper is to shed light, through a real-world case study and from the ethical perspective, on the impacts of implementing such a systemic change in the existing health supply chain systems. As conclusion, a call for more reflexive approaches for the critical examination, as well as more structured guidance for the responsible evaluation, of medical cargo drones is raised. (shrink)

Philosophical interests of Joseph Życiński in the domain of the philosophy of science were focused on the debate concerning the nature of science and philosophy of science that followed the Einstein-Planck revolution in science. The unexpected discovery of the philosophical, extra-scientific presuppositions in science, as well as of the extra-rational factors determining the way these presuppositions are accepted in science were to be explained within the meta-scientific framework. It is the aim of this paper to present ˙ Życiński’s diagnosis of (...) this post-revolutionary situation in the philosophy of science as well as his critique of the metascientific answers to this challenge. The reasons will be given why all those answers are put under two dichotomous rubrics of _internalism_ and _externalism_. It will be also explained how Życiński intends to supersede this false in his opinion opposition with a new concept of the doxatic rationality. However, the details of the metascientific proposal of Życiński will be given only in the subsequent paper. In order to perform the aim of the paper the metatheoretic tools set out by Popper will be used. (shrink)

У статті розглянуті методологічні підходи до визначення сутності та критеріїв класифікації економічних систем. У різноманітті підходів до класифікації економічних систем виділені два основних - формаційний та цивілізаційний. Проаналізовано погляди вчених на співвідношення цих підходів. Аргументована некоректність постановки питання про необхідність доповнити формаційні критерії цивілізаційними критеріями.

_Islamicate Occult Sciences in Theory and Practice_ presents the latest research on Islamic occult sciences from a variety of disciplinary perspectives, namely intellectual history, manuscript studies and material culture.

The Motin family proteins (Motins) are a class of scaffolding proteins consisting of Angiomotin (AMOT), AMOT‐like protein 1 (AMOTL1), and AMOT‐like protein 2 (AMOTL2). Motins play a pivotal role in angiogenesis, tumorigenesis, and neurogenesis by modulating multiple cellular signaling pathways. Recent findings indicate that Motins are components of the Hippo pathway, a signaling cascade involved in development and cancer. This review discusses how Motins are integrated into the Hippo signaling network, as either upstream regulators or downstream effectors, to modulate cell (...) proliferation and migration. The repression of YAP/TAZ by Motins contributes to growth inhibition, whereas subcellular localization of Motins and their interactions with actin fibers are critical in regulating cell migration. The net effect of Motins on cell proliferation and migration may contribute to their diverse biological functions. (shrink)

Noted logician and philosopher addresses various forms of mathematical logic, discussing both theoretical underpinnings and practical applications. After historical survey, lucid treatment of set theory, model theory, recursion theory and constructivism and proof theory. Place of problems in development of theories of logic, logic’s relationship to computer science, more. Suitable for readers at many levels of mathematical sophistication. 3 appendixes. Bibliography. 1981 edition.

Increasingly, humanitarian organizations across the globe have been implementing innovative technologies in their practice as they respond to the needs of communities affected by conflicts, disasters, and public health emergencies. However, technological innovation may intersect with moral values, norms, and commitments, and may challenge humanitarian imperatives. Through the examination of an empirical case study on drone mapping, this paper aims to explore three questions: (1) What are the dynamics between aid delivery and technological innovation in the humanitarian enterprise? (2) How (...) are structural problems addressed in an environment in which technology is being portrayed as a force for change? (3) What moral responsibilities towards vulnerable populations should humanitarian stakeholders bear when introducing innovative technologies in humanitarian action. Discussion revolves around the ideology of “technological utopia”, and the normative role of technology in the aid sector - to make substantive impacts, or to produce “success stories”. In conclusion, a call for rigorous ethical analysis to help foster value sensitive humanitarian innovation (VSHI) is made. (shrink)

The author discusses the meaning of the paradox, which rises as a result of the controversy between the principles of scientific ethos (R. Merton) and fallibilism (K. Popper). She argues that the justification of the moral authority of science should not depend on this paradox. The author uses Max Weber’s concept of substantive rationality to consider the idea of social legitimation of science. She argues for understanding expertise as a special mode of scientific knowledge which aims at justifying the authority (...) of science in the society. (shrink)

The discussion of collective agency involves the reduction problem of the concept of a collective. Individualism and Cartesian internalism have long restricted orthodox theories and made them face the tension between an irreducible concept of a collective and ontological reductionism. Heterodox theories as functionalism and interpretationism reinterpret the concept of agency and accept it as realized on the level of a collective. In order to adequately explain social phenomena that have relations as their essence, in this paper we propose a (...) relational, holistic account of collective agency and argue that functionalism and interpretationism can be integrated into such an account. (shrink)

The recent proposal by the Independent Expert Panel of the Stop Ecocide initiative to include the crime of ecocide in the International Criminal Court's Rome Statute has raised expectations for preventing and remedying severe environmental harm through international prosecution. As alluring as this image is, we argue that ecocide prosecutions may be the most difficult, perhaps even impossible, in precisely the cases that the ICC would need to be concerned with; namely, the gravest global incidents of environmental harm, including those (...) associated with planetary climate change. We explore a series of questions about the panel's formulation of ecocide that resonate with longer debates around criminalizing environmental harm but take on new dimensions amid the Anthropocene and after twenty years of ICC trials. Ecocide must contend with the hard lessons learned concerning the ICC's limitations in realizing justice in a fraught international political context and also with fundamental challenges to knowledge and legitimacy arising from the uncertainty and dynamic socioenvironmental context of the Anthropocene. The proposed amendment, if adopted, risks ineffective prosecutions or even perverse outcomes for the environment itself. This risk, however, may characterize any effort to prosecute ecocide internationally in the Anthropocene unless the terms of international criminal law are fundamentally rethought. (shrink)

Recent years witnessed a growing interest in non-standard epistemic logics of knowing whether, knowing how, knowing what, knowing why and so on. The new epistemic modalities introduced in those logics all share, in their semantics, the general schema of ∃x◻φ, e.g., knowing how to achieve φ roughly means that there exists a way such that you know that it is a way to ensure that φ. Moreover, the resulting logics are decidable. Inspired by those particular logics, in this work, we (...) propose a very general and powerful framework based on quantifier-free predicate language extended by a new modality, which packs exactly ∃x◻ together. We show that the resulting language, though much more expressive, shares many good properties of the basic propositional modal logic over arbitrary models, such as finite-tree-model property and van Benthem-like characterization w.r.t.\ first-order modal logic. We axiomatize the logic over S5 frames with intuitive axioms to capture the interaction between the new modality and know-that operator in an epistemic setting. (shrink)

We study whether greater social trust is associated with a lower incidence of corporate misconduct. Both social norm and network theory suggest that social trust can affect managerial behavior and reduce the likelihood of misconduct behavior. Consistent with this prediction, we find that social trust is negatively associated with corporate misconduct behavior. Moreover, we show that, when media coverage is higher, the negative relation between social trust and corporate misconduct behavior is more pronounced. Further analyses suggest that social trust can (...) help mitigate both disclosure-related and nondisclosure-related misconduct. (shrink)

One of the main problems of modern rationalistic theories of science is the non-eliminability of the subjective factor in the development of science. Temperate rationalism of Newton-Smith was an attempt to solve this problem. J. Życiński developed his own version of temperate rationalism in which the subjective factor played much more substantial role. In the article I am presenting his specific idea of the personal _commitment_ as a necessary condition for rationalism and science. In the first section I proceed to (...) reconstruct ˙ Życiński’s argument leading him to the conclusion of this epistemological necessity. Next in the section 2 I present his idea of the epistemological uncertainty principle as a consequence of the subjective _commitment_. In sections 3 and 4 I explore axiological and pragmatic aspects of the Życiński solution. Finally, in the section 5 I do compare his temperate rationalism with Newton-Smith’s proposal in the context of the Polanyi’s idea of personal knowledge showing differences in their respective approach to the role of the subjective factor in science and rationalism. (shrink)

Numerous societal issues, from climate change to pandemics, require public engagement with scientific research. Such engagement reveals challenges that can arise when experts communicate with laypeople. One of the most common frameworks for framing these communicative interactions is the deficit model of science communication, which holds that laypeople lack scientific knowledge and/or positive attitudes towards science, and that imparting knowledge will fill knowledge gaps, lead to desirable attitude/behavior changes, and increase trust in science. §1 introduces the deficit model in more (...) detail and shows that adhering to this model often fails to achieve its aims, which motivates the main question of this chapter: how can Ludwik Fleck’s theory of thinking collectives address the persistent problem of deficit approaches in science communication? I suggest that it can do so by exposing the deficit model’s implicit assumption of an expert-lay divide. Accordingly, §2 lays out Fleck’s theory and §3 contrasts it with contemporary debates about science communication. Following this descriptive work, §4 draws on Fleck’s ideas to make four concrete suggestions for further questioning the expert-lay divide. (shrink)