Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a “transcriptional switch,” repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to (...) the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. Wnt targets are regulated by a “switch” where TLE co-repressors are displaced from TCFs by β-catenin, leading to activation of transcription. Recent reports challenge this view and suggest that additional processes, including exchange of specific TCF proteins and Wnt-dependent ubiquitination of TLEs, play important roles in the Wnt transcriptional switch. (shrink)

This paper offers three contributions to the burgeoning movements of AI for Social Good (AI4SG) and AI and the United Nations Sustainable Development Goals (SDGs). First, we introduce the SDG-Intense Evaluation framework (SDGIE) that aims to situate variegated automated/AI models in a larger ecosystem of computational approaches to advance the SDGs. To foster knowledge collaboration for solving complex social and environmental problems encompassed by the SDGs, the SDGIE framework details a benchmark structure of data-algorithm-output to effectively standardize AI approaches to (...) the SDGs. Second, as a specific instantiation of the SDGIE framework, the SDG Impact Intensity Model (SDGIIM) is theoretically and operationally established. SDGIIM embeds expert decision-making and SDG keyword banks in textual data processing to determine overall SDG “impact intensity.” Ideally, SDGIIM can be applied to textual data sets from any sector or discipline: academia, business, government, non-profit, civil society, etc. Third, the SDGIIM instantiation is applied to the specific domain of academic journal rating systems as a case study. Traditionally, academic journals have been evaluated on loosely conceived and empirically shaky notions of ‘quality.’ Aligned with the trend of AI4SG and broader calls to action, ‘impact’ is rapidly becoming the primary normative consideration for assessing academic journals. We hypothesize and demonstrate that SDGIIM is capable of producing evaluations aligned with experts’ expectations of SDG impact intensity; the consistent analysis and rating of textual data sets that embody the SDGs with varying degrees of meaning and, ultimately, promote positive impact on the actual material conditions of the world. (shrink)

Insulin is well known for its essential role in carbohydrate metabolism: insulin deficiency results in the development of diabetes mellitus. It has been known for many years that people with diabetes mellitus are predisposed to develop thrombotic diseases including myocardial infarction. It was thought that the thrombus formation was the consequence of impaired carbohydrate metabolism. In recent years, it has become apparent that insulin is capable of ameliorating several pathophysiological events, leading to the inhibition and dissolution of the formed thrombus (...) in the system. These insulin‐induced events include inhibition of platelet aggregation by prompting the synthesis of NO in platelet and prostacyclin in endothelial cells. Furthermore, insulin upregulates prostacyclin receptors and downregulates α2 adrenergic receptor in platelets, thereby amplifying the inhibition of platelet aggregation. Insulin also releases tissue plasminogen activator, a potent thrombolytic enzyme, from the platelet membrane which dissolves the formed thrombus leading to the resumption of normal blood circulation. In effect, insulin could be an essential tool in the control of thrombotic disorders. BioEssays 26:91–98, 2004. © 2003 Wiley Periodicals, Inc. (shrink)

This book brings together ancient spiritual wisdom and modern science and philosophy to address age-old questions regarding our existence, free will and the nature of conscious awareness. Stuart Hameroff MD Professor, Anesthesiology and Psychology, and Director, Center for Consciousness Studies The University of Arizona, Tucson, Arizona This book presents a rich, broad-ranging overview of contemporary research and scholarship into consciousness and the self.... It is... to their credit that the editors have assembled a highly stimulating set of scholars whose expertise (...) cover all the relevant areas. I strongly recommend the book to anyone with an interest in understanding the directions in which contemporary thinking about the nature of consciousness is headed. B. Les Lancaster Emeritus Professor of Transpersonal Psychology Liverpool John Moores University, UK This volume is a collection of 17 essays that contribute to the emerging discipline of consciousness studies with particular focus on the concept of the self. The essays together argue that to understand consciousness is to understand the self that beholds consciousness. Two broad issues are addressed in the volume: the place of the self in the lives of humans and nonhuman primates; and the interrelations between the self and consciousness, which contribute to the understanding of cognitive functions, awareness, free will, nature of reality, and the complex experiential and behavioural attributes of consciousness. The book presents cutting-edge and original work from well-known authors and scholars of philosophy, psychiatry, behavioural sciences and physics. This is a pioneering attempt to present to the reader multiple ways of conceptualizing and thus understanding the relation between consciousness and self in a nuanced manner. (shrink)

Contributed seminar papers organized by National Institute of Advanced Studies in June 2001.

This paper argues that Samuelson's criticisms of Sraffa mainly concentrated on Sraffa's claim that the propositions of his book (Sraffa 1960) did not depend on the assumption of constant returns to scale. Garegnani's defence of Sraffa against Samuelson's criticisms remained ineffective because Garegnani's own interpretation of Sraffa's prices as classical 'centre of gravitation' or 'long term' prices requires constant returns to scale assumption. The paper goes on to critique Garegnani's interpretation of Sraffa and the classical economics to show that Garegnani's (...) interpretation of Sraffa and the classical economics is highly problematic and that Samuelson's criticism of Sraffa does not hit the target because Sraffa's prices are not necessarily 'equilibrium' prices and therefore there is no need of returns to scale assumption in his theory. (shrink)

The following are some of the entries received in the contest presented in our March, 1960 issue. The starred essays were judged as winners and were awarded $25.00 prizes.

Geosciences have been increasingly interested in ethics due to the challenges thrown by advancements of studies and researches in the area of geosciences towards global community. This results in the emergence of a new discipline during the last decade of 20th century named ‘Geo-Ethics’. The great task assigned to this discipline is to provide an ethical face to geosciences so that these may be maximum useful to global community. Although it is very difficult to define any growing discipline and that (...) is the case with geo-ethics, this paper aims to discuss the nature and core principles of this emerging discipline, an amalgamation of geosciences and ethics. Geo-ethics, an application of a value-system in the area of studies and researches of geosciences, is a part of applied ethics. Its proposed principles are: Refrain from superstitions and supernatural affairs, Interconnectedness, Rationality, Non-rigidness and Coherence, Non-maleficence, Beneficence, Justice. (shrink)

Sustainable development is essentially about taking a view of future generations of people inhabiting the world. It is also about defining actions in the present time of achieving the desired goal of bequeathing a livable world for the future. The view has to revolve around how much importance we assign to the well being of future inhabitants. It is an ethical position that we collectively, as the generation living now, have to take. Making moral judgments about the distant future is (...) difficult for two reasons—there is a plurality of ethical positions and building a collective ethic may be impossible. Yet without a shared view we cannot have concerted action now.This article looks at some of the alternative positions and their practical implications for policy actions. The possibility of having a wider, shared ethic is also discussed. The real challenge lies in knowing nature better and making that knowledge part of culture. Then only there could be a convergence in concerns for the future, for Nature and for the yet unborn generations of human beings. (shrink)