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)

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 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)

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 article tries to explore the shifts in contemporary urban Bengali cinema and map and historicize the main trends in relation to changes in the political fortunes of the city. In this context, the article tentatively wishes to accomplish two things: one, to show the main trends in urban Bengali film-making, post-1990s; and two, to read closely two recent Bengali films, in a search for ways of mapping this newness. The article first identifies three new possibilities in Bengali cinema: first, (...) the inward-looking, often apolitical sketches that celebrate liberal development and psychosomatic indulgences, second, the sentimental, community-based films that sometimes take political changes on board as well, and attempt to bridge the rural-urban divide; third, cult-ish films of a newer pedigree that show impatience with old Left and progressive values, and are also technically experimental and avant-garde. The second objective of the article is to discuss specifically two contemporary filmmakers – Moinak Biswas and Suman Mukhopadhay – and place their films within this ferment. (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.

This article tries to explore the shifts in contemporary urban Bengali cinema and map and historicize the main trends in relation to changes in the political fortunes of the city. In this context, the article tentatively wishes to accomplish two things: one, to show the main trends in urban Bengali film-making, post-1990s; and two, to read closely two recent Bengali films, in a search for ways of mapping this newness. The article first identifies three new possibilities in Bengali cinema: first, (...) the inward-looking, often apolitical sketches that celebrate liberal development and psychosomatic indulgences, second, the sentimental, community-based films that sometimes take political changes on board as well, and attempt to bridge the rural-urban divide; third, cult-ish films of a newer pedigree that show impatience with old Left and progressive values, and are also technically experimental and avant-garde. The second objective of the article is to discuss specifically two contemporary filmmakers – Moinak Biswas and Suman Mukhopadhay – and place their films within this ferment. (shrink)

What is the relationship between anger and justice, especially when so much of our moral education has taught us to value the impartial spectator, the cold distance of reason? In _Sing the Rage_, Sonali Chakravarti wrestles with this question through a careful look at the emotionally charged South African Truth and Reconciliation Commission, which from 1996 to 1998 saw, day after day, individuals taking the stand to speak—to cry, scream, and wail—about the atrocities of apartheid. Uncomfortable and surprising, these (...) public emotional displays, she argues, proved to be of immense value, vital to the success of transitional justice and future political possibilities. Chakravarti takes up the issue from Adam Smith and Hannah Arendt, who famously understood both the dangers of anger in politics and the costs of its exclusion. Building on their perspectives, she argues that the expression and reception of anger reveal truths otherwise unavailable to us about the emerging political order, the obstacles to full civic participation, and indeed the limits—the frontiers—of political life altogether. Most important, anger and the development of skills needed to truly listen to it foster trust among citizens and recognition of shared dignity and worth. An urgent work of political philosophy in an era of continued revolution, _Sing the Rage_ offers a clear understanding of one of our most volatile—and important—political responses. (shrink)

Drawing upon the insights of Rabindranath Tagore, who coined the term viswasahitya to express his own understanding of comparative literature, this essay resituates translation as the cornerstone for new directions in world literature. While conventional understandings of world literature tend to reconfirm existing power structures and hierarchies, translation opens up the possibility of thinking beyond the national/global binary by interrogating the lines along which such binaries are conceptualized. Translation operates at the borders that are seen to divide cultures, languages, worldviews (...) and geographies. This essay explores the dynamic relationship between translation and world literature within contemporary South Asian writing, through an analysis of heteroglossia, multilingualism and ‘translatedness’ in selected texts by Mahasweta Devi and Amitav Ghosh, opening up larger questions about multilingualism and also about the very discipline of comparative literature. Highlighting the role that translation has historically played in shaping power relations in the world, this paper projects the transformative potential of translation as the key to a radical reconceptualization of a world literature for the future. (shrink)

Self Learning Material Bachelor of Arts Philosophy Semester Iv BPYC Western Philosophy: Modern Block-2 Rationalism.

The first article in this issue attempts to refute the concept of Altruism and calls it akin to Selfishness. The arguments are logically set in the way like that of Spinoza’s method of demonstration, with Axioms, Definitions, Propositions and Notes: so as to make them exact and precise. Interestingly, the writer introduces a new concept of Credit and through various other original propositions and examples rebuts the altruistic nature which is generally ascribed to humans.

The title seems to suggest that God is neutral or indifferent to the universe that it permeates. Its neutrality being necessary for its immanence is acceptable but not its indifference. Following Spinoza’s monistic thinking we explore here the question as to how the ultimate reality, can or cannot be indifferent to its own self. Permeating the universe, God becomes a universal form or concept into which the human can imagine any version of thought-extension in accordance with the nature of his/her (...) need. Indeed, Spinoza finds God formal it is the supreme substance which can and does inspire man’s polytheistic practices, as sustained by panentheistic faith. Moreover, for Spinoza relation between God and the universe is one of rational causality - God permeates the manifest universe, and the universe through its intelligibility illustrates God. The phrase in the title is not a denial of God’s desirability for man. Rather, it is a reaffirmation of God’s openness to the whole universe, by virtue of which it is one with Nature and vice versa. Each becomes explicable in terms of the other as both seep in rationality validating Spinoza’s ‘deus sive natura’. (shrink)

This paper proposes relative and absolute measures of deprivation using social satisfaction functions. The relative measure gives us the amount by which social satisfaction can be increased in proportional terms by redistributing incomes equally. We also demonstrate the existence of a relationship between summary indices of deprivation and social satisfaction.

In what ways does a society perceive itself as beautiful? Do images of physical perfection indicate aspirations of the social or national body, the perfect body/face emblematic of the collective self-image? In recent years, under conditions of economic and cultural globalization, practices and discourses to render the body beautiful have come under increasing scrutiny. Concerned with the marketing and commodification of body ideals, these studies trace the deleterious effects of advertising, fashion, and celebrity culture in various national and cross-cultural contexts. (...) Yet beauty itself is strangely absent in historical and aesthetic accounts of traditional and new media. In this essay, I try to account for this absence and to provide an alternative view of Indian society's relationship to media images of the body. Using examples from popular cinema, I explore the historical and cultural meanings underlying the fascination with the beautiful. (shrink)

This article makes two arguments. First, that advanced information and communication technologies (ICTs) have created multiple parallel flows of consumption that allow us to be productive continuously, in the sense of generating value for the economy. Second, the struggle over social time poses emergent challenges for planning and urban design. After introducing the relevant themes, this article explains how value is derived from labour and the process through which time is made economically productive. Next, it is posited that advanced ICTs, (...) especially mobile devices and associated services, create possibilities for multiple flows of time, freeing consumption from territorial and temporal restrictions, and opening up new forms of labour. This discussion elicits some concerns for those interested in communities and urban space. The article concludes with suggestions for adopting a socio-spatial-temporal outlook to urban planning and design, including designing ‘polyrhythmic’ places and planning for public time. (shrink)