We suggest a new view of secretory and membrane protein folding that emphasizes the role of pathways of biogenesis in generating functional and conformational heterogeneity. In this view, heterogeneity results from action of accessory factors either directly binding specific sequences of the nascent chain, or indirectly, changing the environment in which a particular domain is synthesized. Entrained by signaling pathways, these variables create a combinatorial set of necessary‐but‐not‐sufficient conditions that enhance synthesis and folding of particular alternate, functional, conformational forms. We (...) therefore propose that protein conformation is productively regulated by the cell during translocation across the endoplasmic reticulum (ER), a concept that may account for currently poorly understood aspects of physiological function, natural selection, and disease pathogenesis. BioEssays 24:741–748, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

ObjectiveOur objective was to evaluate whether those individuals with previous involvement with formal clinical ethics processes differ in their attitudes towards the resolution of prototypical clinical ethics cases than general health care professionals. We hypothesized that those individuals with previous participation in ethics consultation would have significantly different attitudes on the appropriate role of ethics committees in the assessment and resolution of clinical ethical dilemmas than those who have not.MethodsWe conducted a case-based survey of health care professionals at six US (...) hospitals. We administered the survey to health care professionals in a variety of clinical roles at each center and further sub-categorized these by respondents reporting or not reporting their membership on an ethics committee or participation as an ethics consultant/requestor of ethics consult services. Using the analysis of variance test, we present the variation in attitudes using a 5-point Likert scale with 95% confidence intervals and significance set at p ≤ 0.05.ResultsA total of 240 respondents completed the survey (response rate: 63.6%) from all six surveyed centers (128 respondents with involvement with ethics consultation, 112 respondents without). Health care professionals not previously involved with formal clinical ethics processes were less likely to view the ethics committee as having a role in resolving the presented clinical ethical dilemmas ( p = 0.01 for analysis of variance comparison).ConclusionIn this multi-center survey study, health care providers without previous involvement with formal clinical ethics processes were less likely than those with previous involvement to support a role for ethics committees aiding in ethical case resolution. (shrink)

We sought to evaluate whether health care professionals’ viewpoints differed on the role of ethics committees and hospitals in the resolution of clinical ethical dilemmas based on practice location. We conducted a survey study from December 21, 2013 to March 15, 2014 of health care professionals at six hospitals. The survey consisted of eight clinical ethics cases followed by statements on whether there was a role for the ethics committee or hospital in their resolution, what that role might be and (...) case specific queries. Respondents used a 5-point Likert scale to express their degree of agreement with the premises posed. We used the ANOVA test to evaluate whether respondent views significantly varied based on practice location. 240 health care professionals completed the survey. Only three individual queries of 32 showed any significant response variations across practice locations. Overall, viewpoints did not vary across practice locations within question categories on whether the ethics committee or hospital had a role in case resolution, what that role might be and case specific queries. In this multicenter survey study, the viewpoints of health care professionals on the role of ethics committees or hospitals in the resolution of clinical ethics cases varied little based on practice location. (shrink)

A fundamental difference in Svāmi Saccidānandendra Sarasvatī’s (SSS) and the Post-Śaṅkarādvaitins’ (PSA) exegeses of Advaita Vedānta lies in the pedagogic method of adhyāropa-apavāda (deliberate attribution of characteristics to the attribute-less brahman, and its corresponding/complementary contradiction). For SSS, adhyāropāpavāda is the sole method to negate avidyā (ignorance); other Upaniṣadic methods— lakṣaṇā and netivāda —are subsumed under it. For the PSA, on the other hand, adhyāropāpavāda plays a subsidiary, less consequential role in engendering gnosis; the primary role is that of mahāvākyas (the (...) ‘great’ Vedāntic statements). SSS denounces the PSA—with the sole exception of Sureśvarācārya—for their (purportedly incorrect) interpretation of the method; he contends that it has led to the lamentable reification of concepts in Advaita Vedānta, and ultimately undermined its basic tenets. In this article, I articulate SSS’ position. (shrink)

In India, there has been a shift from using unclaimed bodies to voluntary body donation for anatomy dissections in medical colleges. This study used in-depth qualitative interviews to explore the deeper intent, values and attitudes towards body donation, the body and death, and expectations of the body donor, as well as their next of kin and representative religious scholars. All donors had enrolled in a body bequest programme in a medical school in South India. This study concludes that body donors (...) are philanthropists with deep-rooted values of altruism and service, who are often willing to forgo traditional religious and cultural death rituals. The next of kin are often uncomfortable with the donor’s decision, and this suggests that it is important that dialogue/counselling occurs at the time of the bequest, if the donor’s wishes are to be respected. Religious injunctions are often misinterpreted; this implies that religious leaders/scholars can play a significant role in addressing these misconceptions which are barriers to body donation. Body bequest programmes in India may be enhanced by positioning body donation as ‘daana’—giving without any expectation of return for a higher purpose, including ceremonies of respect in medical colleges. Furthermore, increased public engagement and awareness about body bequest programmes are also important to enhance participation. When medical students internalise what body donors expect of them, i.e. altruism, empathy with patients and becoming ‘good doctors’, it will help to ensure that the donation was not in vain and that the dead truly teach the living. (shrink)

STEPHEN TOULMIN George Santayana used to insist that those who are ignorant of the history of thought are doomed to re-enact it. To this we can add a corollary: that those who are ignorant of the context of ideas are doom ed to misunderstand them. In a few self-contained fields such as pure mathematics, concepts and conceptual systems can perhaps be de tached from their historico-cultural situations; so that (for instance) a self-taught Ramanujan, living alone in India, mastered number (...) theory to a point at which he could make major contributions to European mathematics. But elsewhere the situation is different - and, in philosophy, inevitably so. For philosophical ideas and problems confront us like geological specimens in situ; and, in the act of prising them free from their historical and cultural locations, we can too easily forget about the matrix in which they took shape, and end by impossing on them a sculptural form of our own making. Something of this kind has happened in the case of Ludwig Wittgen stein. For his philosophical work has commonly been seen as an episode in the development, either of mathematicallogic, or oftwentieth-century British philosophy. His associations with Frege and Russell, Moore and Waismann, have over-shadowed everything else in his cultural origins and intellectual concerns. (shrink)

Motivated by a large literature on how firm-specific resources drive firm performance, we propose and find that heterogeneity in investor optimism regarding firm-specific attributes plays a very important role in influencing the managerial propensity to manipulate financial statements. When firm-level investor optimism is moderate, the incidence of accounting misconduct increases, but it decreases when investors are highly optimistic. Further, market reaction to the announcement of financial restatements is more negative when investors held more optimistic firm-specific beliefs at the time of (...) initial misstatement. These findings are robust to alternative firm-specific optimism measures linked to analysts, general investors and unsophisticated individual investors, controls for market-wide consumer sentiment unexplained by macroeconomic factors, economy-wide and industry-level optimism, potential selection bias and reverse causality. Our analysis highlights the importance of firm-level investor optimism in predicting, preventing and detecting accounting misconduct. (shrink)

BackgroundCognitive deficits are one of the core features of major depressive disorder that play crucial role in functional recovery. Studies have explored cognitive deficits in MDD, however, given inconsistent results, especially in mild-moderate MDD. Recently, studies have explored music as cognitive ability in various clinical conditions. In MDD, large focus has been on evaluating emotion deficits and just a handful on music cognition. With growing evidence on use of music based intervention to target cognitive deficits, it is imperative to explore (...) nature of music cognitive ability in MDD.AimTo examine musical and neuro-cognitive deficits in patients with mild-moderate MDD.MethodsPatients diagnosed with mild or moderate MDD and matched healthy controls were evaluated on selected tests from NIMHANS Neuropsychological test battery and Montreal battery for evaluation of amusia.ResultsMDD group performed significantly lower than HC on working memory, verbal learning and retention. Three indices were computed for a comprehensive evaluation. Groups did not differ significantly in any of the indices- focused attention, executive function, learning and memory as well as on music cognition. Focused attention and memory index predicted music cognition in HC and the combined group. Attention alone contributed to 62.1% of variance in music cognition. Similarly, music cognition significantly predicted focused attention.ConclusionIndividuals with mild-moderate MDD show significant deficits in working memory, verbal learning and memory, however, not in music cognition. There exists a significant relationship between music cognition and attention, which could be implicated in use of music interventions to ameliorate cognitive deficits. Limitations of study include small sample size and heterogeneity. Future studies on larger cohort examining musical emotion perception and neurocognition is imperative to have deeper understanding of this debilitating condition. (shrink)

The essay is a review discussion of Indian Ethics in the context of a recent volume of essays. The attempt is to identify some of the issues that are now on the frontier of Indian ethics or that are likely to appear on that frontier in the coming years.

The fact that beliefs in the supernatural are useful to people who hold them does not necessarily mean that these beliefs confer an evolutionary advantage to those who hold them. An evolutionary explanation for any biological phenomenon must meet rigorous criteria, but the facts in this case, even when taken at their face value, fall well short of these criteria.

Mental time travel is a principled, but a narrow and computationally limiting, implementation of foresight. Future events can be predicted with sufficient specificity without having to have episodic memory of specific past events. Bayesian estimation theory provides a framework by which one can make predictions about specific future events by combining information about various generic patterns in the past experience.

The proteasome is a proteolytic complex that is known to degrade proteins marked by the attachment of ubiquitin. Recently, it has become apparent that the proteasome has non-proteolytic roles. Several studies have implicated the proteasome in the regulation of transcription. A new study now shows that the proteasome facilitates the interaction of a histone acetyltransferase complex with transcriptional activators at active promoters.1 Bioessays 28:235–239, 2006. © 2006 Wiley Periodicals, Inc.

Global forest loss is highest in the tropical region, an area with high biological biodiversity. As some of these forests are part of indigenous forest management, it is important to pay attention to such management, its values and practices for better conservation. This paper focuses on sacred freshwater swamp forests of the Western Ghats, India, and with it a faith-based approach to nature conservation. Drawing on fieldwork and focus groups, we present the rituals and rules that structure the governance of (...) sacred swamps. We also discuss in depth the ecological, socio-cultural and economic valuation of these freshwater swamps by various local groups. In this way, we show overlaps and differences of valuation among different groups. In the context of a secular state with a diversity of faith groups and migration dynamics, we propose that faith-based governance of sacred swamps can benefit from the emphasis of faith-independent, 'accessible' ecological, socio-cultural and economic values to foster a dialogue around sacred swamps and their place for livelihoods and nature conservation. (shrink)

Ocherk 1. Voprosy ontologii -- Ocherk 2. Voprosy ėtiki i ėstetiki -- Ocherk 3. Voprosy gnoseologii i aksiologii.

The essay is a review discussion of Indian Ethics in the context of a recent volume of essays. The attempt is to identify some of the issues that are now on the frontier of Indian ethics or that are likely to appear on that frontier in the coming years.

Mission-oriented climate change research is often unverifiable. Therefore, many stakeholders look to peer-reviewed climate change research for trustworthy information about deeply uncertain and impactful phenomena. This is because peer-review signals that research has been vetted for scientific standards like reproducibility and replicability. Here we evaluate the transparency of research methodologies in mission-oriented computational climate research. We find that only five percent of our sample meets the minimal standard of fully open data and code required for reproducibility and replicability. The widespread (...) lack of minimal openness standards in peer-reviewed climate change research jeopardizes scientific credibility and risks poor societal outcomes as we manage growing climate risks. The scientific community can and must do better. We, the authors, outline necessary openness standards that we commit to as researchers, reviewers, and readers. We invite you to join us. (shrink)

Ariès traces Western man's attitudes toward mortality from the early medieval conception of death as the familiar collective destiny of the human race to the modern tendency, so pronounced in industrial societies, to hide death as if it were an embarrassing family secret.

This remarkable book--the fruit of almost two decades of study--traces in compelling fashion the changes in Western attitudes toward death and dying from the earliest Christian times to the present day. A truly landmark study, The Hour of Our Death reveals a pattern of gradually developing evolutionary stages in our perceptions of life in relation to death, each stage representing a virtual redefinition of human nature. Starting at the very foundations of Western culture, the eminent historian Phillipe Aries shows how, (...) from Graeco-Roman times through the first ten centuries of the Common Era, death was too common to be frightening; each life was quietly subordinated to the community, which paid its respects and then moved on. Aries identifies the first major shift in attitude with the turn of the eleventh century when a sense of individuality began to rise and with it, profound consequences: death no longer meant merely the weakening of community, but rather the destruction of self. Hence the growing fear of the afterlife, new conceptions of the Last Judgment, and the first attempts (by Masses and other rituals) to guarantee a better life in the next world. In the 1500s attention shifted from the demise of the self to that of the loved one (as family supplants community), and by the nineteenth century death comes to be viewed as simply a staging post toward reunion in the hereafter. Finally, Aries shows why death has become such an unendurable truth in our own century--how it has been nearly banished from our daily lives--and points out what may be done to "re-tame" this secret terror. The richness of Aries's source material and investigative work is breathtaking. While exploring everything from churches, religious rituals, and graveyards (with their often macabre headstones and monuments), to wills and testaments, love letters, literature, paintings, diaries, town plans, crime and sanitation reports, and grave robbing complaints, Aries ranges across Europe to Russia on the one hand and to England and America on the other. As he sorts out the tangled mysteries of our accumulated terrors and beliefs, we come to understand the history--indeed the pathology--of our intellectual and psychological tensions in the face of death. (shrink)

Prologue, invitation to thinking about God In the Hebrew Bible? -- Part I, questions about God? -- Why does God in the Bible have a body? -- What do God's body parts in the Bible mean? -- Why is God angry in the Bible? -- Does God in the Bible have gender or sexuality? -- Part II, questions about God in the world? -- What can creation tell us about God? -- Who-or what-is the Satan? -- Why do people suffer (...) according to the Hebrew Bible? -- Epilogue, God in the Bible and beyond. (shrink)

"Sir Hermann Bondi, NatureThe late S. Chandrasekhar was best known for his discovery of the upper limit to the mass of a white dwarf star, for which he received ...

This chapter develops a perceptual solution to the epistemological problem of other minds, relying on central ideas from Maurice Merleau-Ponty's phenomenology. The Merleau-Pontian account is contrasted with another attempted perceptual solution to the other minds problem, and it is argued that only the former meets the phenomenologists' desideratum of providing an alternative to inferential solutions. The chapter also provides responses to various objections to the perceptual solution, including a pair of objections recently put forward by Alec Hyslop.

Richard Janko's acclaimed translation of Aristotle's _Poetics_ is accompanied by the most comprehensive commentary available in English that does not presume knowledge of the original Greek. Two other unique features are Janko's translations with notes of both the _Tractatus Coislinianus_, which is argued to be a summary of the lost second book of the Poetics, and fragments of Aristotle’s dialogue On Poets, including recently discovered texts about catharsis, which appear in English for the first time.

Many books explain what is known about the universe. This book investigates what cannot be known. Rather than exploring the amazing facts that science, mathematics, and reason have revealed to us, this work studies what science, mathematics, and reason tell us cannot be revealed. In The Outer Limits of Reason, Noson Yanofsky considers what cannot be predicted, described, or known, and what will never be understood. He discusses the limitations of computers, physics, logic, and our own thought processes. Yanofsky describes (...) simple tasks that would take computers trillions of centuries to complete and other problems that computers can never solve; perfectly formed English sentences that make no sense; different levels of infinity; the bizarre world of the quantum; the relevance of relativity theory; the causes of chaos theory; math problems that cannot be solved by normal means; and statements that are true but cannot be proven. He explains the limitations of our intuitions about the world -- our ideas about space, time, and motion, and the complex relationship between the knower and the known. Moving from the concrete to the abstract, from problems of everyday language to straightforward philosophical questions to the formalities of physics and mathematics, Yanofsky demonstrates a myriad of unsolvable problems and paradoxes. Exploring the various limitations of our knowledge, he shows that many of these limitations have a similar pattern and that by investigating these patterns, we can better understand the structure and limitations of reason itself. Yanofsky even attempts to look beyond the borders of reason to see what, if anything, is out there. (shrink)