Regulated secretory proteins are stored within specialized vesicles known as secretory granules. It is not known how proteins are sorted into these organelles. Regulated proteins may possess targeting signals which interact with specific sorting receptors in the lumen of the trans‐Golgi network (TGN) prior to their aggregation to form the characteristic dense‐core of the granule. Alternatively, sorting may occur as the result of specific aggregation of regulated proteins in the TGN. Aggregates may be directed to secretory granules by interaction of (...) a targeting signal on the surface with a sorting receptor. Novel targeting signals which confer on regulated proteins a tendency to aggregate under certain conditions, and in so doing cause them to be incorporated into secretory granules, have been implicated. Specific targeting signals may also play a role in directing membrane proteins to secretory granules. (shrink)

Clonal expansion of T‐lymphocyte populations results from interactions of antigenic structures presented in combination with accessory cells (macrophages) and antibody recognition sites on the surface of T cells. The resulting activation of a membrane phospholipase C plays a crucial role in lymphocyte responses by releasing diglyceride and PIP3. The released diglyceride activates a cellular protein kinase C while PIP3 stimulates Ca2+ influx. Arachidonic acid released by the action of diglyceride lipase serves as substrate for the synthesis of bioactive eicosanoids (prostaglandins (...) and leukotrienes) which in turn modulate cellular adenyl and guanyl cyclases. The eicosanoids serve as both intra‐ and extra‐cellular signals for lymphocytes, regulating the production and expression of lymphokines and mediating the complex interactions between the monocyte‐macrophage components and helper and suppressor T cells.Aspirin and other anti‐inflammatory drugs stimulate mitogenesis by inhibiting production of the negative modulator prostaglandin E2 in accessory cells and by enhancing the production of the lymphokine 1L‐2 by producer T‐cells. (shrink)

The years from 1918 to 1945 remain central to European History. It was a breath-taking time during which the very best and very worst attributes of Mankind were on display. In the euphoria of peace which followed the end of the First World War, the Baltic States emerged as independent forces on the world stage, participating in thrilling experiments in national and transnational governance. Later, following economic collapse and in the face of rising totalitarianism among even Europe’s most cultured nations, (...) Baltic communities succumbed to nationalism too. During wartime, Baltic peoples became both victims and, sometimes, victimisers. Ultimately their victimhood lasted until the end of the Cold War, yielding consequences still discernible at the start of the twenty first century. Taking the period 1918 to 1945 as pivotal, this collection of essays examines some of the key themes in Baltic History as they are emerging today. These include appreciations of identity, autonomy and the rights of national minorities; the everyday and social foundations of international security; and the importance of historical memory to popular and political identities. (shrink)

Using fictionalized case studies this series follows four patients through the medical process, from onset through Diagnosis, Treatment and PrognosisVolume 1: Symptom. Examines the idea of 'symptom' as a route to understanding the structure of clinical practice -- Volume 2: Diagnosis. Explores the meaning of 'diagnosis' as a complex, culturally mediated interaction between individuals, scientific discoveries, social negotiation and historical change. -- Volume 3: Treatment. Considers the concept of treatment as an active process which produces an outcome, be it effective, (...) inappropriate or inadequate. Enlightening reading. -- Volume 4: Prognosis. Contemplates the challenge of the prognosis, attempting to make sense of life and death. Considers, through personal and professional perspectives, the role of the medical profession in guiding patient experience.--. (shrink)

Media reporting of science has consequences for public debates on the ethics of research. Accordingly, it is crucial to understand how the sciences of the brain and the mind are covered in the media, and how coverage is received and negotiated. The authors report here their sociological findings from a case study of media coverage and associated reader comments of an article from Annals of Neurology. The media attention attracted by the article was high for cognitive science; further, as associates/members (...) of the Centre where it was produced, the authors of the research reported here had rare insight into how the scientists responsible for the Annals of Neurology article interacted with the media. The data corpus included 37 news items and 228 readers’ comments, examined via qualitative thematic analysis. Media coverage of the article was largely accurate, without merely copying the press release. Analysis of reader comments showed these to be an important resource for considering issues of import to neuroethics scholars, as well as to scientists themselves. In particular, the findings demonstrate how personal experiences were vital in shaping readers’ accounts of their agreements with the scientific article. Furthermore, the data show how scientific research can catalyse political discussions in ways likely unanticipated by scientists. The analysis indicates the importance of dialogue between journalists, laboratory scientists and social scientists in order to support the communication of the messages researchers intend. (shrink)

Galatians is a clear witness to a basic conviction of Paul: the gospel is not about human movement into blessedness, but about God's liberating invasion of the cosmos. Christ's love enacted in the cross has the power to change the world because it is embodied in the new community of mutual service.

Since its founding in 1943, Medievalia et Humanistica has won worldwide recognition as the first scholarly publication in America to devote itself entirely to medieval and Renaissance studies. Since 1970, a new series, sponsored by the Modern Language Association of America and edited by an international board of distinguished scholars and critics, has published interdisciplinary articles. In yearly hardbound volumes, the new series publishes significant scholarship, criticism, and reviews treating all facets of medieval and Renaissance culture: history, art, literature, music, (...) science, law, economics, and philosophy. (shrink)

The criterion of truth is the measure of the truthfulness and reliability of our knowledge. It is also the basis for determining the correctness of our concepts and how much our perceptions, ideas, and concepts accord with objective reality. Idealism holds to the idea that the criterion of truth does not involve the integration between theory as created by human intelligence and objective reality, but rather that the criterion of truth involves the "clarity and correctness" of perception, viewpoints, and concepts (...) by the subject. For instance, the Machists 1 think that the criterion of truth is experience, however, they neither interpret experience from a materialistic viewpoint, nor view experience as the result of humans interacting with nature as they reform it. The Machists view experience as a summary of perceptions and as the subjective experience of humans. In this sense, perception must be tested by perception itself. In attempting to escape the trap of solipsism , they proposed "collective experience" as the criterion of truth. According to such a view, anything that involves "common significance," that is, anything acknowledged by everyone, is the truth. Lenin exposed the absurdity of idealist theory by pointing out that by following the view of "socially formed experience" it is very easy to consider as normal the most absurd and farcical notions, such as ghosts, for such beliefs are also a form of human "experience." Religion also possesses a "common significance," for innumerable people believe in ghosts and miracles, etc. Nevertheless, religion does not become the truth because of this. The concept of the "criterion of truth" held by the Machists played a dominant role in modern bourgeois philosophy. Jean Jacques Rousseau and John Dewey, along with other reactionaries in philosophy all denied scientific criteria. They would rather that the masses remain ignorant of how to understand and determine the truth. (shrink)

This book outlines the realist and pluralist philosophy of John Anderson, Australia's most original thinker. His teaching at Sydney University and his arti6es have deeply influenced Australian intellectual life. Several main themes run through his work, but Anderson never gave an overall account of his views. This is remedied here: exhibiting the range of Anderson's thought from logic, epistemology and theory of mind, to language and social theory, this volume sketches realism as a systematic philosophical position, while showing something of (...) the history of ideas in Australia. (shrink)

"The philosophical works of A. J. Ayer": p. [334]-341. Bibliography: p. [343]-346. Includes indexes.

I want to discuss a view of punishment which stresses its ‘expressive’ character and seeks in that its justification. While I shall label this view ‘expressionism’, I should warn that most theorists who express an ‘expressionist’ view do not present it as an exhaustive account, but rather claim to be highlighting an aspect that tends to be neglected within the rationalist framework common to retributivism and utilitarianism. Among contemporary writings I shall focus on Joel Feinberg's article, ‘The Expressive Function of (...) Punishment’ in The Monist 49, No. 4 . While I accept that ‘expression’ usefully sums up much of what underlies punitive practices, I shall urge that the term conceals a variety of more or less amalgamated ingredients which need to be disentangled for critical inspection. I shall argue that under those aspects, punishment's justification continues to be elusive. I do not imagine that these arguments will deter my more punitive colleagues from continuing to seek such justification, but I hope they will search elsewhere. Feinberg writes: Punishment is a conventional device for the expression of attitudes of resentment and indignation, and of judgments of disapproval and reprobation, either on the part of the punishing authority himself or of those ‘in whose name’ the punishment is inflicted. Punishment, in short, has a symbolic significance largely missing from other kinds of penalties. (shrink)

This essay seeks to characterise the essential features of an equitable health care system in terms of the classical Aristotelian concepts of horizontal and vertical equity, the common language of “need” and the economic notion of cost-effectiveness as a prelude to identifying some of the more important issues of value that policy-makers will have to decide for themselves; the characteristics of health that can cause policy to be ineffective ; the information base that is required to support a policy directed (...) at securing greater equity, and the kinds of research that are needed to underpin such a policy. (shrink)

The issue of directed donation of organs from deceased donors for transplantation has recently risen to the fore, given greater significance by the relatively stagnant rate of deceased donor donation in the UK. Although its status and legitimacy is explicitly recognized across the USA, elsewhere a more cautious, if not entirely negative, stance has been taken. In England, Wales and Northern Ireland, the Human Tissue Act 2004, and in Scotland the Human Tissue (Scotland) Act 2006, are both silent in this (...) regard. Although so-called conditional donation, donation to (or perhaps withheld from) a specific class, has been outlawed as a product of guidance issued by the Secretary of State for Health issued in the wake of the controversial incident occurring in the North of England in 1998, its intended application to ‘directed’ donation is less certain. Directed and conditional donations challenge the traditional construct of altruistic donation and impartial (equitable) allocation in a very immediate and striking fashion. They implicitly raise important questions as to whether the body or parts of the body are capable of being owned, and by whom. This paper attempts to explore the notion of donor ownership of body parts and its implications for both directed and conditional donation. (shrink)

Recent policy in relation to clinical research proposals in the UK has distinguished between two types of review: scientific and ethical. This distinction has been formally enshrined in the recent changes to research ethics committee structure and operating procedures, introduced as the UK response to the EU Directive on clinical trials. Recent reviews and recommendations have confirmed the place of the distinction and the separate review processes. However, serious reservations can be mounted about the science/ethics distinction and the policy of (...) separate review that has been built upon it. We argue here that, first, the science/ethics distinction is incoherent, and, second, that RECs should not only be permitted to consider a study’s science, but that they have anobligation do so. (shrink)

We attempt to discern what Badioursquo;s philosophical system provides for thinking of education in a form which separates it from its contemporary representation in the state. These notes oppose to this state form Badiou#39;s declaration that #39;the only education is an education by truthsrsquo;. We pursue this in three sections. First, we will address the significance and function of the term lsquo;conditionsrsquo;. Secondly we will address Badioursquo;s essay lsquo;Art and Philosophyrsquo; from Handbook of Inaesthetics, the only essay in fact where (...) Badiou addresses education in a specific manner and in which Badiou discusses the link between art and philosophy in terms of the lsquo;pedagogical themersquo;: A theme, he says, that has been brought to collapse. Thirdly we will attempt to discern what might make up whatnbsp; Badiou refers to as the lsquo;fourth modalityrsquo; of the link between philosophy and its conditions through a somewhat speculative discussion of the dual lsquo;militantrsquo; praxis known in Badioursquo;s work as lsquo;subtractionrsquo; and lsquo;forcingrsquo;. (shrink)

A number of recent papers have described the successful derivation of egg and sperm precursor cells from mouse embryonic stem cells—so-called “artificial” gametes. Although many scientific questions remain, this research suggests numerous new possibilities for stem cell research and assisted reproductive technology, if a similar breakthrough is achieved with human embryonic stem cells. The novel opportunities raised by artificial gametes also prompt new ethical questions, such as whether same-sex couples should be able to access this technology to have children who (...) are genetically related to them both.THE CREATION OF “ARTIFICIAL” GAMETESOver the past two years, a number of papers have been published detailing the first successful attempts at differentiating mouse embryonic stem cells into egg1 and sperm2 precursor cells. Previously, researchers had used embryonic stem cells to generate tissues such as brain, liver, and pancreatic cells, but not germ cells of any kind. Production of gamete precursor cells was achieved initially through allowing stem cell lines to differentiate more or less randomly, but recent research has focused on identifying the precise ways in which differentiation into gametes can be precipitated and controlled. These breakthroughs make it seem likely that ongoing research on human stem cells will yield similar possibilities,3 raising questions over the practicalities of what might be achieved with such “artificial” gametes. In turn, the novel opportunities presented by artificial gametes raise a number of ethical concerns.The initial breakthrough, namely the obtaining of egg cells from mouse stem cells, was achieved by means of relatively simple science. Rather than coaxing stem cells to develop into eggs using complicated cocktails of growth factors, researchers adopted standard cell culture conditions, but grew the cells at higher density than usual.3–6 Growing the cells in this way led to the formation of ovary-like cell aggregates, which (when separated and stimulated with …. (shrink)