Signal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being a member of the extracellular signal‐regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by the inflammatory cytokines TNF‐α and IL‐1‐β, as well as by a wide variety of cellular stresses such as UV and ionizing radiation, hyperosmolarity, heat stress, oxidative stress, etc. One pathway converges on the ERK subfamily known as the ‘stress activated’ protein kinases (...) (SAPKs, also termed Jun N‐terminal kinases, JNKs), whereas the second pathway recruits the p38 kinases. Upstream inputs are diverse, and include small GTPases (primarily Rac and Cdc42; secondarily Ras) acting through mammalian homologs of the yeast Ste20 kinase, other kinase subfamilies (e.g. GC kinase) and ceramide, a putative second messenger for certain TNF‐α actions. These two cascades signal cell cycle delay, cellular repair or apoptosis in most cells, as well as activation of immune and reticuloendothelial cells. (shrink)

The Hippo pathway, a cascade of protein kinases that inhibits the oncogenic transcriptional coactivators YAP and TAZ, was discovered in Drosophila as a major determinant of organ size in development. Known modes of regulation involve surface proteins that mediate cell‐cell contact or determine epithelial cell polarity which, in a tissue‐specific manner, use intracellular complexes containing FERM domain and actin‐binding proteins to modulate the kinase activities or directly sequester YAP. Unexpectedly, recent work demonstrates that GPCRs, especially those signaling through Galpha12/13 such (...) as the protease activated receptor PAR1, cause potent YAP dephosphorylation and activation. This response requires active RhoA GTPase and increased assembly of filamentous (F‐)actin. Morever, cell architectures that promote F‐actin assembly per se also activate YAP by kinase‐dependent and independent mechanisms. These findings unveil the ability of GPCRs to activate the YAP oncogene through a newly recognized signaling function of the actin cytoskeleton, likely to be especially important for normal and cancerous stem cells. (shrink)

The thesis of the present volume is critical and dual. (1) Present day philosophy of man and sciences of man suffer from the Greek mis taken polarization of everything human into nature and convention which is (allegedly) good and evil, which is (allegedly) truth and fal sity, which is (allegedly) rationality and irrationality, to wit, the polar ization of all fields of inquiry, the natural and social sciences, as well as ethics and all technology, whether natural or social, into the (...) totally positive and the totally negative. (2) Almost all philosophy and sci ences of man share the erroneous work ethic which is the myth of man's evil nature - the myth of the beast in man, the doctrine of original sin. To mediate or to compromise between the first view of human nature as good with the second view of it as evil, sociologists have devised a modified utilitarianism with deferred gratification so called, and the theory of the evil of artificial competition (capitalist and socialist alike) and of keeping up with the Joneses. Now, the mediation is not necessary. For, the polarization makes for abstract errors which are simplistic views of rationality, such as reductionism and positivism of all sorts, as well as for concrete errors, such as the disposition to condemn repeatedly those human weaknesses which are inevitable, namely man's inability to be perfectly rational, avoid all error, etc. , thus setting man against himself as all too wicked. (shrink)

Climate models calibrated exclusively with observations from the 19th through 21st centuries are unsuitable for assessing many important hypotheses about the future. Many systems in the modern climate are expected to cross dynamic thresholds in the near future, requiring more than the instrumental record for adequate calibration. In this paper I argue that paleoclimate analogues from earth’s past can mitigate this threshold problem, even if the modern climate exhibits features that make it historically unique. While this requires that paleoclimatologists be (...) increasingly discriminate in the past systems they target for modern analogues, the upshot is a practice of climate model construction that improves the reliability of future projections. All of this is achieved by integrating features of past climate systems discovered by the study of earth deep in the past. My analysis synthesizes important empirical work done by climate modelers and paleoclimatologists with relevant philosophical work on analogical reasoning in science. (shrink)

In September 2003, we released the first results of a national community attitude tracking study about child abuse and child protection. At that time, we concluded that as a community, violence against children was tolerated. The community did not understand or appreciate the seriousness, size and cost of child abuse in Australia. There was evidence that child abuse was not viewed as an important challenge facing children in Australia. A second study conducted in 2006 found that nothing much had changed, (...) indeed community engagement with the issue of child abuse may have even deteriorated. A third study in 2010 found that the community actively avoids the problem of child abuse rating it less concerning than high petrol prices. In 2021, 18 years after the first report was published, we have concluded again that child abuse remains out of sight and out of mind as a community concern. This article describes the findings of this fourth iteration of our survey and analyses the implications for ensuring that individuals are more engaged and committed to taking action to preventing child abuse and/or protecting children from violation. (shrink)

Background The globalization of clinical research in the last two decades has led to a significant increase in the volume of clinical research in developing countries. As of 2016, Uganda was the third largest destination for clinical trials in Africa. This requires adequate capacity and systems to facilitate ethical practice. Methods This was a retrospective study involving review of laws, guidelines, policies and records from 1896 to date. Results Modern medicine evolved from 1896 and by the time of Uganda's independence (...) in 1962, a 1500 bed national referral hospital was in place and a fully‐fledged medical school was established at the Makerere University. As the practice of medicine evolved in the country, so did medical research that addressed priority health issues. The growth in modern medicine was not matched with development of research infrastructure and regulatory systems. The first documented regulation of research activities was in 1970 while the first research ethics committee established in 1986 was to facilitate review of research related to the HIV/AIDs pandemic. In 1990 an Act of Parliament was passed to facilitate development and implementation of policies, hence the development of the national guidelines in 1997, training, establishment and accreditation of research ethics committees, conferences and research site monitoring. Conclusion Over the past 120 years, the implementation and structural aspects of research ethics in Uganda have evolved through 70 years of no regulation, followed by 30 years of rudimentary regulation while the last 20 years have shown significant growth in the regulatory system associated with supportive laws, institutionalization of regulatory and training processes. (shrink)

In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the International Declaration on Human Genetic Data (2003) and the Universal Declaration on the Human Genome and Human Rights (1997) is useful, if not necessary, in engaging in (...) decision making in relation to the moral evaluation of biotechnologies on a global scale. (shrink)

Social Constructivism and the Philosophy of Science by Andre Kukla The Social Construction of What? by Ian Hacking.

Does thinking have a history? If there are no necessarily changeless structures to be found in things and in our inquiry into them, then what knowledge of the world and ourselves is possible? In this boldly original and elegantly written study, Joseph Margolis argues for a radically historicized view of history that treats it as both a real process and a narrative account, each a product of continual change. Developing his argument through discussions of such influential philosophers of history (...) and the natural sciences as Vico, Danto, Collingwood, Habermas, Hempel, Popper, Putnam, and Gadamer, he provides a coherent theory of flux and invariance that resolves several deep puzzles regarding human nature and understanding. While maintaining a thorough command of Anglo-American philosophy, Margolis challenges many of its most cherished assumptions and demonstrates the sense in which history and interpretation are one and the same. Exploring one of the master themes of this century, his book offers a novel theory of the human condition whose conclusions and concerns seem certain to inform philosophy in the next century as well. (shrink)

A variety of approaches have appeared in academic literature and in design practice representing “ethics-first” methods. These approaches typically focus on clarifying the normative dimensions of design, or outlining strategies for explicitly incorporating values into design. While this body of literature has developed considerably over the last 20 years, two themes central to the endeavour of ethics and values in design (E + VID) have yet to be systematically discussed in relation to each other: (a) designer agency, and (b) the (...) strength of normative claims informing the design process. To address this gap, we undertook a structured review of leading E + VID approaches and critiques, and classified them according to their positions on normative strength, and views regarding designer agency. We identified 18 distinct approaches and 13 critiques that met the inclusion criteria for our review. Included papers were distributed across the spectrum of views regarding normative strength, and we found that no approaches and only one critique represented a view characteristic of “low” designer agency. We suggest that the absence of “low” designer agency approaches results in the neglect of crucial influences on design as targets of intervention by designers. We conclude with suggestions for future research that might illuminate strategies to achieve ethical design in information mature societies, and argue that without attending to the tensions raised by balancing normatively “strong” visions of the future with limitations imposed on designer agency in corporate-driven design settings, “meaningful” ethical design will continue to encounter challenges in practice. (shrink)

This survey of major developments in North American philosophy of science begins with the mid-1960s consolidation of the disciplinary synthesis of internalist history and philosophy of science (HPS) as a response to criticisms of logical empiricism. These developments are grouped for discussion under the following headings: historical metamethodologies, scientific realisms, philosophies of the special sciences, revivals of empiricism, cognitivist naturalisms, social epistemologies, feminist theories of science, studies of experiment and the disunity of science, and studies of science as practice and (...) culture. A unifying theme of the survey is the relation between historical metamethodologists and scientific realists, which dominated philosophical work in the late 1970s. I argue that many of the alternative cognitive naturalisms, social epistemologies, and feminist theories that have been proposed can be understood as analogues to the differences between metamethodological theories of scientific rationality and realist accounts of successful reference to real causal processes. Recent work on experiment, scientific practice, and the culture of science may, however, challenge the underlying conception of the field according to which realism and historical rationalism (or their descendants) are the important alternatives available, and thus may take philosophy of science in new directions. (shrink)

Philosophers wanted commonsense to fight skepticism. They hypostasized and destroyed it. Commonsense is skeptical--Bound by a sense of proportion and of limitation. A scarce commodity, At times supported, At times transcended by science, Commonsense has to be taken account of by the critical-Realistic theory of science. James clerk maxwell's view of today's science as tomorrow's commonsense is the point of departure. It is wonderful but overlooks the value of the sense of proportion.

Analogies have been traditionally recognized as a proper part of inductive procedures, akin to generalizations. Seldom, however, have they been presented as superior to generalizations, in the attainability of a higher degree of certitude for their conclusions or in other respects. Though Bacon definitely preferred analogy to generalization, the tradition seems to me to go the other way—until the recent publication of works by Mary B. Hesse and, perhaps, R. Harré.

In Wittgenstein on Meaning, Colin McGinn argues that the skeptical argument that Kripke distills from Wittgenstein's rule-following considerations generates at most what might be called meaning skepticism (the non-factuality view of meaning), and not concept skepticism (the non-factuality view of concepts). If correct, this would mean the skeptical reasoning is far less significant than Kripke thinks. Others have seemed to agree with McGinn. I argue that McGinn is wrong here--that, in fact, Kripke's skeptical reasoning has a straightforward extension to concepts. (...) Whether the reasoning succeeds, however, is another matter, which I do not address here. (shrink)

Ever since the publication of Placide Tempel's epoch-making work Bantu Philosophy, African philosophers have worked to dispel the myth that there is no metaphysics in Africa.

This book is a first attempt to cover the whole area of aesthetics from the point of view of critical rationalism. It takes up and expands upon the more narrowly focused work of E. H. Gombrich, Sheldon Richmond, and Raphael Sassower and Louis Ciccotello. The authors integrate the arts into the scientific world view and acknowledge that there is an aesthetic aspect to anything whatsoever. They pay close attention to the social situatedness of the arts. Their aesthetics treats art as (...) emerging from craft in the form of luxurious and playful challenge to the audience. In developing it they place emphasis on the number of questions and claims that can be settled by appeal to empirical facts; on the historical character of aesthetic judgements; and on the connection of aesthetic truth to true love and true friendship, i.e. fidelity and integrity, not to informative truth. (shrink)

Economics is a science - at least positive economics must be. And science is in part applied mathematics, in part empirical observations and tests. Looking at the history of economics, one cannot find much testing done before the twentieth century, and even the collection of data, even in the manner Marx engaged in, was not common in his day. It is true that economic policy is an older field, and in that field much information is deployed for the purpose of (...) prescribing a course of action. But this is not to say that the information procured for that purpose is either based on observation or has been tested. In the seventeenth century some alchemists and economists hoped to boost the economy by manufacturing gold, others feared inflation; and the British Parliament legislated against manufacturing gold. David Hume proved in the eighteenth century - quite a priori - that doubling the quantity of gold will only double the price of each commodity and he thus set things at rest for a while. Later the question was opened again when Marx, for example, showed historically how the gold robbed from the Americas started Europe's boom. Yet the theory - the quantity theory of money, as it is called - which Hume proved a priori, is still contested and still hardly tested to economists' satisfaction: is the price level fixed mainly by the amount of available money? Some economists answer yes, others no. (shrink)

Epistemological issues have inevitably been perennial issues for theism. For any claim to have insight into the nature and acts of the divine requires some sort of substantiation. And the appeal to faith typically made to meet this demand is often unconvincing. This raises a fundamental question: what could constitute proper grounds for theistic belief? In attempting to anwser this question, we will need to address the underlying epistemic issue of what justifies commitment to any world–view.

Volume 3, Issue 1, March 2019, Page 81-85.

ḥ. 1. Beʼurim ʻal ha-ketuvim u-maʼamre Razal -- ḥ. 2. Derushim u-musarim le-Shabatot ha-shanah -- ḥ. 3. Ḥi. Mas. Berakhot.

Rather than just offer background readings or a survey of views on a subject, as traditional anthologies do, this volume tries to engage the reader’s active participation in understanding how philosophy came to be split between analytic and continental approaches and in finding ways to reconcile the two. It does so by tracing the history of philosophy as a perennial contest between two opposing world views: one that relates change to an underlying structure of invariance, and another that sees change (...) itself as the basic condition of existence. The seven chapters cover the full range of major topics of philosophy, from metaphysics to epistemology to ethics, and present carefully selected readings from key thinkers—Plato, Aristotle, Locke, Hegel, and Peirce up to Heidegger, Husserl, Kuhn, Kripke, and Putnam, among others—juxtaposed and introduced by the editors so as to stimulate active thinking about how the debate between these competing visions plays out in each arena. A bibliography of additional sources ends each chapter. The result is a new and inspiring tool for teaching philosophy to both beginning and advanced students. Even seasoned professionals will have much to learn about the development of philosophy and its current predicament from accepting the challenge to rethink the tradition from the perspective presented here. (shrink)