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)

Niranjan Ramakrishnan examines the surprising extent to which Gandhi's writings still provide insight into current global tensions and the assumptions that drive them. This book explores how ideas Gandhi expressed over a century ago can be applied today to issues from terrorism to the environment, globalization to the 'Clash of Civilizations.' In particular it looks at Gandhi's emphasis on the small, the local, and the human – an emphasis that today begins to appear practical, attractive, and even inescapable. Written (...) in an accessible style invoking examples from everyday happenings familiar to all, this concise volume reintroduces Gandhi to today's audiences in relevant terms. (shrink)

The major challenge in complex disease genetics is to understand the fundamental features of this complexity and why functional alterations at multiple independent genes conspire to lead to an abnormal phenotype. We hypothesize that the various genes involved are all functionally united through gene regulatory networks (GRN), and that mutant phenotypes arise from the consequent perturbation of one or more rate‐limiting steps that affect the function of the entire GRN. Understanding a complex phenotype thus entails unraveling the details of each (...) GRN, namely, the transcription factors that bind to cis regulatory elements affected by sequence variants altering transcription of specific genes, and their mutual feedback relationships. These GRNs can be identified through their rate‐limiting steps and are best uncovered by genomic analyses of rare, extreme phenotype families, thus providing a coherent molecular basis to complex traits and disorders. (shrink)

The role of various organizational pressures in influencing performance of firms has been an interesting research topic in a variety of fields and has received the attention of researchers working in the field of environmental strategy. Although there are previous studies that have looked at the influence of various pressures in influencing firms’ environmental strategies, our study provides a more holistic analysis considering a variety of such pressures in a single framework. We discuss a research study to analyze how pressures (...) from internal and external stakeholders of a firm, economic pressures, environmental regulations, and pressures of environmental compliance have affected environmental performance of firms using data collected from manufacturing firms in the United Kingdom. We have found that internal stakeholders provide the greatest impact in shaping environmental performance of firms, closely followed by economic pressures, environmental regulations, and external stakeholders in that order. Fears of penalties due to environmental compliance have the least impact, although this pressure also has a positive and significant impact on environmental performance. (shrink)

The present paper is primarily concerned with the application of the transformative approach within the Western philosophical context. My aim is to show how the idea of a transformation is present in Platonic thought based on John Taber’s work on transformative philosophy. According to Taber, transformative thinkers tell us that the unreflecting mind lives in a dream and, if it is to know the truly real, one “must awaken from the dream, enliven slumbering faculties, make a transition to a new (...) state of awareness.” I will use the Platonic dialogue to illustrate how some of the main features of transformative philosophy developed by Taber are exhibited there, if only to emphasize the transformative aspect of Platonic philosophy, although not dismiss the systematic reading of Platonic texts. (shrink)

Derek Parfit, who died in 2017, is widely believed to have been the best moral philosopher in well over a century. The twenty new essays in this book were written in his honour and have all been inspired by his work - in particular, his work in an area of moral philosophy known as 'population ethics', which is concerned with moral issues raised by causing people to exist. Until Parfit began writing about these issues in the 1970s, there was almost (...) no discussion of them in the entire history of philosophy. But his monumental book 'Reasons and Persons' (1984) revealed that population ethics abounds in deep and intractable problems and paradoxes that not only challenge all the major moral theories but also threaten to undermine many important common-sense moral beliefs. (shrink)

The one great quality of Socratic gift is that thinking as an activity continues but not repetitively but every time thinking takes place, it takes place a new. Thinking is the one activity that cannot be repeated like prayers and other pieties. All philosophical thinking is new thinking; it has to be new in order to be thinking. Philosophy had to become the handmaid of sociology and could not be allowed to remain surrogate sociology. When this happened new concepts or (...) new conceptualizations became the need of the hour: in the place of the age-old hierarchic social stratification a novel concept of materialism had to be inducted - after all matter is what matters. And in India morally entangled sociology was holding down the rich human resources of the sub-continent and a development-oriented ideology had to convert this moral society into a legal society: An unlegislated, unlegislatable society is condemned to be unstable andcollapsible; in its place a stable, legislatable society had to be created. With this felt-need Dr. Ambedkar came into the Indian political arena and gave a modernist rethinking to the outmoded Indian social structure: His hallmark was think to change. (shrink)

The one great quality of Socratic gift is that thinking as an activity continues but not repetitively but every time thinking takes place, it takes place a new. Thinking is the one activity that cannot be repeated like prayers and other pieties. All philosophical thinking is new thinking; it has to be new in order to be thinking. Philosophy had to become the handmaid of sociology and could not be allowed to remain surrogate sociology. When this happened new concepts or (...) new conceptualizations became the need of the hour: in the place of the age-old hierarchic social stratification a novel concept of materialism had to be inducted - after all matter is what matters. And in India morally entangled sociology was holding down the rich human resources of the sub-continent and a development-oriented ideology had to convert this moral society into a legal society: An unlegislated, unlegislatable society is condemned to be unstable andcollapsible; in its place a stable, legislatable society had to be created. With this felt-need Dr. Ambedkar came into the Indian political arena and gave a modernist rethinking to the outmoded Indian social structure: His hallmark was think to change. (shrink)

The one great quality of Socratic gift is that thinking as an activity continues but not repetitively but every time thinking takes place, it takes place a new. Thinking is the one activity that cannot be repeated like prayers and other pieties. All philosophical thinking is new thinking; it has to be new in order to be thinking. Philosophy had to become the handmaid of sociology and could not be allowed to remain surrogate sociology. When this happened new concepts or (...) new conceptualizations became the need of the hour: in the place of the age-old hierarchic social stratification a novel concept of materialism had to be inducted - after all matter is what matters. And in India morally entangled sociology was holding down the rich human resources of the sub-continent and a development-oriented ideology had to convert this moral society into a legal society: An unlegislated, unlegislatable society is condemned to be unstable andcollapsible; in its place a stable, legislatable society had to be created. With this felt-need Dr. Ambedkar came into the Indian political arena and gave a modernist rethinking to the outmoded Indian social structure: His hallmark was think to change. (shrink)

On Vedanta philosophy based on Śaṅkarācārya's commentary on Bhagavadgītā, Brahmasūtra, and Upanishads.

This volume, an important contribution to dialogic and Bakhtin studies, shows the natural fit between Bakhtin’s ideas and the pluralistic culture of India to a global academic audience. It is premised on the fact that long before principles of dialogism took shape in the Western world, these ideas, though not labelled as such, were an integral part of intellectual histories in India. Bakhtin’s ideas and intellectual traditions of India stand under the same banner of plurality, open-endedness and diversity of languages (...) and social speech types and, therefore, the affinity between the thinker and the culture seems natural. Rather than being a mechanical import of Bakhtin’s ideas, it is an occasion to reclaim, reactivate and reenergize inherent dialogicality in the Indian cultural, historical and philosophical histories. Bakhtin is not an incidental figure, for he offers precise analytical tools to make sense of the incredibly complex differences at every level in the cultural life of India. Indian heterodoxy lends well to a Bakhtinian reading and analysis and the papers herein attest to this. The papers range from how ideas from Indo-European philology reached Bakhtin through a circuitous route, to responses to Bakhtin’s thought on the carnival from the philosophical perspectives of Abhinavagupta, to a Bakhtinian reading of literary texts from India. The volume also includes an essay on ‘translation as dialogue’ – an issue central to multilingual cultures – and on inherent dialogicality in the long intellectual traditions in India. (shrink)

Transcript of papers on culture, philosophy, doctrines and other facets Buddhism; presented at a conference held in March, 2006 at Jai Narain Vyas University, organized by Bauddha Adhyayana Kendra.

On Sankhya philosophy; Sanskrit text with Hindi translation.

We show, for various classes of totally ordered structures, including o‐minimal and weakly o‐minimal structures, that every definable partial order on a subset of extends definably in to a total order. This extends the result proved in for and o‐minimal.

To understand the variations in the financial characteristics, we examine the dynamical behaviors by considering the chaotic financial model with external force. First, the dynamical characteristics are analyzed by introducing the external driven force in the price index with commodity demand. We discover that the presence of an external force causes the alternate occurrence of oscillatory and steady states as a function of time. Interestingly, we find the existence of bifurcation delay during the transition from oscillatory to steady state or (...) vice versa. Bifurcation delay is a phenomenon in which the bifurcation does not occur at the actual bifurcation point but rather at a later time, which is referred to as bifurcation delay. To confirm the delay in bifurcation, we estimate the actual bifurcation point and compare it to the observed bifurcation transition. Furthermore, to understand the variations in the bifurcation delay, we estimate the delay time between each consecutive cycle and find random fluctuations in the BD. Following that, the BD is virtualized via a transformed phase portrait. In addition, we show decreasing the value of average BD while increasing the frequency of external forcing. Second, the presence of BD is explored by incorporating external forces into the investment demand with unit investment cost. We discover the existence of a similar phenomenon with a constant bifurcation delay. (shrink)

A proper elementary extension of a model is called small if it realizes no new types over any finite set in the base model. We answer a question of Marker, and show that it is possible to have an o-minimal structure with a maximal small extension. Our construction yields such a structure for any cardinality. We show that in some cases, notably when the base structure is countable, the maximal small extension has maximal possible cardinality.

Dynamical analysis, chaos suppression and electronic implementation of the synchronous reluctance motor without external inputs are investigated in this paper. The different dynamical behaviors found in the SynRM without external inputs are illustrated in the two parameters largest Lyapunov exponent diagrams, one parameter bifurcation diagram, and phase portraits. The three single controllers are designed to suppress the chaotic behaviors found in SynRM without external inputs. The three proposed single controllers are simple and easy to implement. Numerical simulation results show that (...) the three proposed single controllers are effective. Finally, the dynamical behaviors found in the SynRM without external inputs and the physical feasibility of the three proposed single controllers are validated through circuit implementation on OrCAD-PSpice software. (shrink)

We prove that a function definable with parameters in an o-minimal structure is bounded away from ∞ as its argument goes to ∞ by a function definable without parameters, and that this new function can be chosen independently of the parameters in the original function. This generalizes a result in [1]. Moreover, this remains true if the argument is taken to approach any element of the structure , and the function has limit any element of the structure.

The nature of the relationship between environmental performance and firm performance of corporations is a long standing and contentious issue in the literature. This study is intended to advance this debate by arguing for the existence of curvilinear relationship and empirically testing the same using survey data on UK manufacturing firms. FP is captured in terms of growth in sales and market share. Our results show evidence for a quadratic relationship—as firms improve their EP, they seem to achieve much higher (...) levels of FP. These results are consistent with the resource-based view of a firm; as firms engage in EP activities, they are able to gain inimitable knowledge that helps in further learning to further improve performance. Based on our results, we suggest that new studies focus on strategies to extend the period of increasing returns and maximizing the benefits of the positive association between EP and FP. (shrink)

The Homeobox (Hox) genes essentially define body regions in all animals including humans – responsible for determining two arms, two legs, one nose and so on. This gene is shared by all living beings – from the snail to the elephant to humans – and it can now be manipulated into transforming certain parts of the body into others. We have observed such transformations, such as that of an amputated antenna into a limb, as far back as 1901, termed neomorphosis (...) (Morgan 1901), and it has only recently re-emerged as an area of scientific study. Spontaneous transformations and induced regenerations are fascinating research topics that are fast becoming a reality; some scientists are postulating that it may be possible that the hox gene could be central to limb regeneration in the future. This article will present the Hox Zodiac project, which attempts to introduce this subject and push the ideas further into speculation of mutation (i.e. humans and animals) into creatures that may resemble the mythical beings we know as fiction. The starting point of this wheel of life is the Chinese zodiac, consisting of twelve animals that are associated with humans. In the process of development, it became interesting to note that half of the animals on the wheel are those used in the lab – rat, pig, monkey, dog, sheep and rabbit. The ox, tiger, horse, snake and rooster are considered mythical and the dragon could easily fall into the category of a genetically modified creature that is to re-emerge in the future. Since medical and scientific testing on humans is strictly forbidden, scientists have virtually shifted to animals for all such studies. Thus, everything that is used on our bodies and minds is directly related to the animal kingdom. The pig heart and rat mind are symbols for the paradox of science that uses animals in ways that are at once disconnected while subconsciously connecting us more than ever by using research results in medical and food products we consume. Although the controversy of using animals in labs is widely known and often violently opposed, the artist in the lab questions how this research impacts our collective consciousness, especially with the growing trend of brain-computer interfaces and particularly synthetic telepathy. This relationship of the human to the metaphorical meaning of the animal kingdom brought to mind Jung’s research on metaphors, symbolism and archetypes, which became central to the Hox Zodiac. (shrink)

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

We prove that in an arbitrary o-minimal structure, every interpretable group is definably isomorphic to a definable one. We also prove that every definable group lives in a cartesian product of one-dimensional definable group-intervals. We discuss the general open question of elimination of imaginaries in an o-minimal structure.

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem cell biology pose (...) unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established. **NB we did not reccommend a NAC, we think it might be appropriate**. (shrink)