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)

Históricamente, los estudios de desastres han presentado dos comprensiones antagónicas de las catástrofes: singularidades extremas que producen historia o procesos que perpetúan estructuras sociopolíticas e inequidades. Mediante un análisis del terremoto de 1970 en Ancash, Perú, y su influencia en la implementación de discursos de (des)aceleración en medio de grandes transformaciones en la sociedad peruana, este artículo presenta una comprensión alternativa de los desastres más allá de la disrupción y continuidad, para enfocarse en las articulaciones temporales que estos producen. Al (...) ser concebidos como dispositivos temporales, los desastres tienen la capacidad de reestructurar ritmos, escalas y temporalidades de manera heterogénea y múltiple. El artículo pretende aportar argumentos que, aunque basados en el terremoto de Ancash, pueden aplicarse a otros debates sobre catástrofes, crisis y desastres como desencadenantes de aceleración y desaceleración económica, social o cultural. (shrink)

According to the Appraisal-Tendency Framework (Han, Lerner, & Keltner, 2007), certainty-associated emotions increase risk taking compared with uncertainty-associated emotions. To date, this general effect has only been shown in static judgement and decision-making paradigms; therefore, the present study tested the effect of certainty on risk taking in a sequential decision-making task. We hypothesised that the effect would be reversed due to the kind of processing involved, as certainty is considered to encourage heuristic processing that takes into account the emotional cues (...) arising from previous decisions, whereas uncertainty leads to more systematic processing. One hundred and one female participants were induced to feel one of three emotions (film clips) before performing a decision-making task involving risk (Game of Dice Task; Brand et al., 2005). As expected, the angry and happy participants (certainty-associated emotions) were more likely than the fearful participants (uncertainty-associated emotion) to make safe decisions (vs. risky decisions). (shrink)

Meta-learning is learning to learn, which includes the development of capacities to transfer what people learned in one specific domain to other domains. It facilitates finetuning learning parameters and setting priors for effective and optimal learning in novel contexts and situations. Recent advances in research on artificial intelligence have reported meta-learning is essential in improving and optimizing the performance of trained models across different domains. In this paper, I suggest that meta-learning plays fundamental roles in practical wisdom and its cultivation (...) within moral domains. I support my argument with findings from studies in psychology, neuroscience, and computer science. Moreover, I suggested concrete ideas for moral education to foster wisdom cultivation along with meta-learning with evidence from studies across various fields. Particularly, I underscored that exemplars, including role models and mentors, play fundamental roles in education. Finally, I discussed the potential implications of the introduction of the concept, meta-learning, to moral education addressing concerns and issues related to socio-cultural diversity. (shrink)

In this chapter, we integrate three distinct strands of thought to argue that the concept of “fairness” varies significantly across cultures. As a result, ensuring that human-AI interactions meet relevant fairness standards requires a deep understanding of the cultural contexts in which AI-enabled systems are deployed. Failure to do so will not only result in the generation of unfair outcomes by an AI-enabled system, but it will also degrade legitimacy of and trust in the system. The first strand concerns the (...) dominant approach taken in the technology industry to ensure that AI-enabled systems are fair. This approach is to reduce fairness to some mathematical formalism that can be applied universally, a quintessentially Western conception of fairness. The second strand concerns alternative conceptions of fairness that have their roots in philosophical traditions of the East, namely Confucian virtue ethics. Understanding how individuals from diverse cultural backgrounds perceive fairness—particularly their beliefs about fairness in human-to-human interactions—is crucial for understanding how they will interpret fairness in human-AI interactions. Building on these philosophical and behavioral differences, as highlighted by empirical research, the third strand integrates insights from political science and interdisciplinary studies. This perspective offers valuable guidance on designing AI-enabled systems to align with contextually relevant standards of fairness. Examining existing beliefs about fairness within the context of institutional decision-making provides valuable insights into what people expect from AI-generated decisions. These expectations often include key elements such as a sufficient degree of transparency, clear lines of accountability, and mechanisms to contest decisions made by the system—all of which are essential components of procedural fairness. Rather than adopting a one-size-fits-all approach to ensuring fairness, the design and deployment of AI systems must carefully account for the operating environment, including the socio-political and cultural context, to ensure that the system aligns with the relevant standards of fairness. (shrink)

Abstract: This paper identifies two central paradoxes threatening the notion of amor fati [love of fate]: it requires us to love a potentially repellent object (as fate entails significant negativity for us) and this, in the knowledge that our love will not modify our fate. Thus such love may seem impossible or pointless. I analyse the distinction between two different sorts of love (eros and agape) and the type of valuation they involve (in the first case, the object is loved (...) because we value it; in the second, we value the object because we love it). I use this as a lens to interpret Nietzsche's cryptic pronouncements on amor fati and show that while an erotic reading is, up to a point, plausible, an agapic interpretation is preferable both for its own sake and because it allows for a resolution of the paradoxes initially identified. In doing so, I clarify the relation of amor fati to the eternal return on the one hand, and to Nietzsche's autobiographical remarks about suffering on the other. Finally, I examine a set of objections pertaining both to the sustainability and limits of amor fati, and to its status as an ideal. (shrink)

Volumi e saggi Jay Schulkin, Reflections on the Musical Mind. An Evolutionary Perspective , [Michele Gardini, p. 202] • Hans Belting, Faces. Eine Geschichte des Gesichts [Pietro Conte, p. 205] • Aby Warburg, Il primo Rinascimento italiano. Sette conferenze inedite [Alice Barale, p. 207] • Laura Anna Macor , Reading Schiller: Ethics, Aesthetics and Religion [Lorenzo Leonardo Pizzichemi, p. 209] • Bernard Lafargue, Stéphanie Cardoso , Figures de l’art n° 25, Philosophie du design [Claire Azéma, Anne Beyaert Geslin, Stéphanie Cardoso, (...) Cécile Croce, p. 212] • Helmut Leder et al., What Makes an Art Expert? Emotion and Evaluation in Art Appreciation , “Cognition and Emotion”, 2013, 28, pp. 1-11; Enric Munar et al., Aesthetic Appreciation: Event-Related Field and Time-Frequency Analyses , “Frontiers in Human Neurosciences”, 2012, 5, pp. 1-11; Gerald C. Cupchik et al., Viewing Artworks: Contributions of Cognitive Control and Perceptual Facilitation to Aesthetic Experience , “Brain and Cognition”, 2009, 70, pp. 84-91 [Gianluca Consoli, p. 217]. (shrink)

Perhaps the year 1996 will be entered in history as an important year in Sino-American relations.

Analyses the exegetical strategies of the Neoplatonist Simplicius.

Our competitive, service-oriented societies are taking a toll on the late-modern individual. Rather than improving life, multitasking, "user-friendly" technology, and the culture of convenience are producing disorders that range from depression to attention deficit disorder to borderline personality disorder. Byung-Chul Han interprets the spreading malaise as an inability to manage negative experiences in an age characterized by excessive positivity and the universal availability of people and goods. Stress and exhaustion are not just personal experiences, but social and historical phenomena as (...) well. Denouncing a world in which every against-the-grain response can lead to further disempowerment, he draws on literature, philosophy, and the social and natural sciences to explore the stakes of sacrificing intermittent intellectual reflection for constant neural connection. (shrink)

Lorsque Socrate dit : " Connais-toi toi-même ", il veut que je me connaisse, non pas métaphysiquement, non pas dans mon essence, non pas dans ce qui est insaisissable, mais dans ce qui est saisissable ; il veut que je sache ce que je suis, ce que je veux et ce que je peux. La connaissance individualiste de moi-même comprend la double critique de ma volonté et de ma puissance.

BackgroundFear of cancer recurrence is an important cause of suffering for cancer survivors, and both empirical evidence and theoretical models suggest that prognostic uncertainty plays a causal role in its development. However, the relationship between prognostic uncertainty and FCR is incompletely understood.ObjectiveTo explore the relationship between prognostic uncertainty and FCR among patients with ovarian cancer.DesignA qualitative study was conducted utilizing individual in-depth interviews with a convenience sample of patients with epithelial ovarian cancer who had completed first-line treatment with surgery and/or (...) chemotherapy. Semi-structured interviews explored participants’ understanding of their prognosis; experiences, preferences, and attitudes regarding prognostic information; and strategies for coping with prognostic uncertainty. Inductive qualitative analysis and line-by-line software-assisted coding of interview transcripts was conducted to identify key themes and generate theoretical insights on the relationship between prognostic uncertainty and FCR.ResultsThe study sample consisted of 21 participants, nearly all of whom reported experiencing significant FCR, which they traced to an awareness of the possibility of a bad outcome. Some participants valued and pursued prognostic information as a means of coping with this awareness, suggesting that prognostic uncertainty causes FCR. However, most participants acknowledged fundamental limits to both the certainty and value of prognostic information, and engaged in various strategies aimed not at reducing but constructing and maintaining prognostic uncertainty as a means of sustaining hope in the possibility of a good outcome. Participants’ comments suggested that prognostic uncertainty, fear, and hope are connected by complex, bi-directional causal pathways mediated by processes that allow patients to cope with, construct, and maintain their uncertainty. A provisional dual-process theoretical model was developed to capture these pathways.ConclusionAmong patients with OC, prognostic uncertainty is both a cause and an effect of FCR—a fear-inducing stimulus and a hope-sustaining response constructed and maintained through various strategies. More work is needed to elucidate the relationships between prognostic uncertainty, fear, and hope, to validate and refine our theoretical model, and to develop interventions to help patients with OC and other serious illnesses to achieve an optimal balance between these states. (shrink)

Gross domestic product can well reflect the development of the economy, and predicting GDP can help better grasp the future economic trends. In this article, three different neural network models, the genetic algorithm – back-propagation neural network model, the particle swarm optimization – Elman neural network model, and the bat algorithm – long short-term memory model, were analyzed based on neural networks. The GDP data of Sichuan province from 1992 to 2020 were collected to compare the performance of the three (...) models in predicting GDP. It was found that the mean absolute percentage error values of the three models were 0.0578, 0.0236, and 0.0654, respectively; the root-mean-square error values were 0.0287, 0.0166, and 0.0465, respectively; and the PSO-Elman NN model had the best performance in GDP prediction. The experimental results demonstrate that neural networks were reliable in predicting GDP and can be used for further applications in practice. (shrink)

This article examines how Muslim religious scholars find space within political and legal discourses to deal with thorny issues such as rebellion. It takes as its case study a treatise by Ibn al-Jawzī regarding the permissibility to curse the second Umayyad caliph Yazīd b. Muʿāwiya. Although written to address the cursing of Yazīd, the treatise also speaks to questions regarding rulership and rebellion. Overall, the article argues that Ibn al-Jawzī adopted a juristically prudent approach to rebellion against an unjust and (...) sinful ruler which synthesizes various elements of the Sunni caliphate discourse and the Islamic legal discourse on the treatment of rebels. This allowed him to shift the debate from one on the permissibility of rebellion to one on the question of legitimacy, thus enabling him to justify actions against Yazīd without overtly condoning the act of rebellion. (shrink)

The challenging competitive situation in the market forces the organizations to recognize the crucial role of branding. Many studies focused on financial and customer perspectives and ignored the importance of employee-based brand building in the organization. Employee-based brand equity plays a vital role in increasing organizational performance. Hence, this study puts effort into brand-building and recognized many factors that develop employee-based brand equity for organizations. This study examines the role of internal knowledge dissemination and employees-based brand equity through brand identification (...) and emotional attachment. This study also assesses the direct relationship between internal knowledge dissemination and brand identification, internal knowledge dissemination and emotional attachment, brand identification and employee-based brand equity, and emotional attachment and employee-based brand equity. For this purpose, this study adopts a convenient sampling technique and questionnaire survey method and gathered data with 712 sample sizes from employees of various clothing brands in China. For empirical examination of the data, this study considers the partial least square structural equation modeling technique and analyzed data using the Smart PLS 3.3.3 software. The outcomes revealed that internal knowledge dissemination negatively influences employee-based brand equity. This study finds a positive direct association between internal knowledge dissemination and brand identification, internal knowledge dissemination and emotional attachment, brand identification and employee-based brand equity, and emotional attachment and employee-based brand equity. Moreover, this study finds that emotional attachment and brand identification positively mediate the relationship between internal knowledge dissemination and employee-based brand equity. The findings of this study provide an insight to the organizations that effective dissemination of the internal knowledge enhances employees’ brand identification and their emotional attachments. Consequently, these positive attributes of employees play a constructive role in creating employee-based brand equity. This study also has some valuable theoretical and practical implications. (shrink)

The present study aimed to develop effective moral educational interventions based on social psychology by using stories of moral exemplars. We tested whether motivation to engage in voluntary service as a form of moral behavior was better promoted by attainable and relevant exemplars or by unattainable and irrelevant exemplars. First, experiment 1, conducted in a lab, showed that stories of attainable exemplars more effectively promoted voluntary service activity engagement among undergraduate students compared with stories of unattainable exemplars and non-moral stories. (...) Second, experiment 2, a middle school classroom-level experiment with a quasi-experimental design, demonstrated that peer exemplars, who are perceived to be attainable and relevant to students, better promoted service engagement compared with historic figures in moral education classes. (shrink)