Ran is one of the most abundant and best conserved of the small GTP binding and hydrolyzing proteins of eukaryotes. It is located predominantly in cell nuclei. Ran is a member of the Ras family of GTPases, which includes the Ras and Ras‐like proteins that regulate cell growth and division, the Rho and Rac proteins that regulate cytoskeletal organization and the Rab proteins that regulate vesicular sorting. Ran differs most obviously from other members of the Ras family in both its (...) nuclear localization, and its lack of sites required for post‐translational lipid modification. Ran is, however, similar to other Ras family members in requiring a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity. In this review, the multiple cellular functions of Ran are evaluated with respect to its known biochemistry and molecular interactions. (shrink)

RECENT PHILOSOPHICAL ATTENTION TO THE LANGUAGE OF DISEASE HAS FOCUSED PRIMARILY ON THE QUESTION OF ITS VALUE-NEUTRALITY OR NON-NEUTRALITY. PROPONENTS OF THE VALUE-NEUTRALITY THESIS SYMBOLICALLY COMBINE POLITICAL AND OTHER CRITICISMS OF MEDICINE IN AN ATTACK ON WHAT THEY SEE AS VALUE-INFECTED USES OF DISEASE LANGUAGE. THE PRESENT ESSAY ARGUES AGAINST TWO THESES ASSOCIATED WITH THIS VIEW: A METHODOLOGICAL THESIS WHICH TENDS TO DIVORCE THE ANALYSIS OF DISEASE LANGUAGE FROM THE CONTEXT OF THE PRACTICE OF MEDICINE AND A SUBSTANTIVE THESIS WHICH (...) HOLDS THAT DISEASE LANGUAGE IS EVALUATIVELY NEUTRAL. IN PARTICULAR, THE ESSAY CRITICALLY FOCUSES ON THE VALUE NEUTRAL POSITION ADOPTED BY CHRISTOPHER BOORSE, WHICH HE TERMS A FUNCTIONAL THEORY OF DISEASE. THE ARGUMENT CONCERNS WHETHER OR NOT ONE CAN HAVE VALUE NEUTRAL DESCRIPTION OF DISEASE STATES OR WHETHER DISEASE LANGUAGE ESSENTIALLY INVOLVES VALUES. (shrink)

Volume 19, Issue 6, June 2019, Page 1-3.

In this response, George Ellis comments on the publications of Part IV. He responds first to James Woodward, Richard Healey, Jan Voosholz, Simon Friederich and Sach Mukherjee, before outlining his thoughts on Max Kistler’s piece.

PREFACE. THE Author of this very practical treatise on Scotch Loch - Fishing desires clearly that it may be of use to all who had it. He does not pretend to have written anything new, but to have attempted to put what he has to say in as readable a form as possible. Everything in the way of the history and habits of fish has been studiously avoided, and technicalities have been used as sparingly as possible. The writing of this (...) book has afforded him pleasure in his leisure moments, and that pleasure would be much increased if he knew that the perusal of it would create any bond of sympathy between himself and the angling community in general. This section is interleaved with blank shects for the readers notes. The Author need hardly say that any suggestions addressed to the case of the publishers, will meet with consideration in a future edition. We do not pretend to write or enlarge upon a new subject. Much has been said and written-and well said and written too on the art of fishing but loch-fishing has been rather looked upon as a second-rate performance, and to dispel this idea is one of the objects for which this present treatise has been written. Far be it from us to say anything against fishing, lawfully practised in any form but many pent up in our large towns will bear us out when me say that, on the whole, a days loch-fishing is the most convenient. One great matter is, that the loch-fisher is depend- ent on nothing but enough wind to curl the water, -and on a large loch it is very seldom that a dead calm prevails all day, -and can make his arrangements for a day, weeks beforehand whereas the stream- fisher is dependent for a good take on the state of the water and however pleasant and easy it may be for one living near the banks of a good trout stream or river, it is quite another matter to arrange for a days river-fishing, if one is looking forward to a holiday at a date some weeks ahead. Providence may favour the expectant angler with a good day, and the water in order but experience has taught most of us that the good days are in the minority, and that, as is the case with our rapid running streams, -such as many of our northern streams are, -the water is either too large or too small, unless, as previously remarked, you live near at hand, and can catch it at its best. A common belief in regard to loch-fishing is, that the tyro and the experienced angler have nearly the same chance in fishing, -the one from the stern and the other from the bow of the same boat. Of all the absurd beliefs as to loch-fishing, this is one of the most absurd. Try it. Give the tyro either end of the boat he likes give him a cast of ally flies he may fancy, or even a cast similar to those which a crack may be using and if he catches one for every three the other has, he may consider himself very lucky. Of course there are lochs where the fish are not abundant, and a beginner may come across as many as an older fisher but we speak of lochs where there are fish to be caught, and where each has a fair chance. Again, it is said that the boatman has as much to do with catching trout in a loch as the angler. Well, we dont deny that. In an untried loch it is necessary to have the guidance of a good boatman but the same argument holds good as to stream-fishing... (shrink)

Featuring essays by some of the most prominent names in contemporary political and cultural theory, _Sovereignty in Ruins_ presents a form of critique grounded in the conviction that political thought is itself an agent of crisis. Aiming to develop a political vocabulary capable of critiquing and transforming contemporary political frameworks, the contributors advance a politics of crisis that collapses the false dichotomies between sovereignty and governmentality and between critique and crisis. Their essays address a wide range of topics, such as (...) the role history plays in the development of a politics of crisis; Arendt's controversial judgment of Adolf Eichmann; Strauss's and Badiou's readings of Plato's _Laws_; the acceptance of the unacceptable; the human and nonhuman; and flesh as a biopolitical category representative of the ongoing crisis of modernity. Altering the terms through which political action may take place, the contributors think through new notions of the political that advance countermodels of biopolitics, radical democracy, and humanity. Contributors. Judith Butler, George Edmondson, Roberto Esposito, Carlo Galli, Klaus Mladek, Alberto Moreiras, Andrew Norris, Eric L. Santner, Adam Sitze, Carsten Strathausen, Rei Terada, Cary Wolfe. (shrink)

It’s never too early to give young boys a resource that will help them learn the skills for making right choices in life. A Boy’s Guide to Making Really Good Choices is designed to help boys ages 8-12 learn how to think through their options, realize the possible consequences, and develop good decision-making skills. In this book, Jim George uses helpful stories and illustrations to walk boys through the kinds of choices they are likely to face each day—choices to... (...) listen to their parents do their best in school, sports, and activities select friends with care be kind to siblings and others help out at home and use good manners Through the use of real-life scenarios, Jim George equips boys to build good character—the kind that will stay with them for life and honor God’s standards. (shrink)

The history of philosophy is replete with attempts at invoking rationality as a means of directing and even subduing human desire and emotion. Understood as that which moves human beings to action, desire and emotion come to be associated with human freedom and rationality as a means of curbing that freedom. Plato, for instance, takes for granted a separation between thought and action that drives a wedge between our rational ability to exercise self-discipline and the free expression of desire and (...) emotion. Hobbes, on the other hand, replaces our internal ability for rational self-control with the external authority of the political State. So long as freedom and control are pitted against one another, human beings are incapable of attaining a symbiosis of these two elements of human action so essential to realizing true democracy. Unlike Plato, John Dewey sees in democracy the greatest potential for individual and social life. The purpose of this dissertation is to demonstrate how the educational philosophy of Dewey, which culminates in an educational aesthetic, appeals to and makes the most of the symbiosis of freedom and self-control, emotion and reason. Dewey’s educational aesthetic not only offers an alternative to traditional methods of education, but also demonstrates how the goal of a democratic way of life is made feasible by means of intelligently guided self-discipline—a form of self-control guided by intelligence that is not a constraint upon freedom, but instead embodies greater opportunity for freedom. I trace the basis for this synthesis, in the social-political and pedagogical principles of John Locke and Jean-Jacques Rousseau. Both Locke and Rousseau offer educational theories that begin turning our attention toward the essential partnership required of rationality and emotion. Dewey's educational aesthetic is then considered as a response to alienating forms of education that continue to pit control and freedom against one another, and which thwart the intellectual and emotional development necessary for autonomy and democratic forms of social organization. (shrink)

In view of the overwhelming weight of the manuscript evidence, including most recently the testimony of Y, it is perhaps about time to stop the attempts at emendation that began in the sixteenth century with sed non blanda puto. The weaknesses, too, of the argument in favour of lengthening metri gratia the final vowel of blanda have been clearly pointed out by Housman,1 who just as clearly pointed out that blanda must therefore be an ablative.

From the standpoint of modern medicine, death is a failure—and one of the first things that we learn in the 2016 movie Doctor Strange is that Stephen Strange does not like to fail. Stephen Strange in many ways epitomizes the unflattering picture that the stereotypes paint of a spiritually desolate West. If the West is hyper‐rationalist and obsessed with subduing the forces of nature, the East of popular imagination is where one goes to gain the wisdom that begins with surrendering (...) control and accepting the limits of reason. The philosopher Friedrich Nietzsche would say that the Hinterweltler's depiction of Dormammu and the nightmarish consequences of inviting him into this world reveal the hope for eternity to be grounded in a hatred of life. The sorcerer Kaecilius, rogue disciple and nemesis of the Ancient One, also aspires to “a world beyond time, beyond death”, where mortal beings can enjoy “eternal life as part of the one”. (shrink)

This chapter contains sections titled: Bad Desire Ignorant Desire Knowledgeable Desire Further Reading.

Shortcuts to goals are rewarded by faster attainment and punished by more frequent failure, so selection of the various kinds – heuristics, cached sequences (habits or macros), gut instincts – depends on reward history just like other kinds of choice. The speeds of shortcuts lie on continua along with speeds of deliberation, and these continua have no obvious separation points.

First published in 2002. Routledge is an imprint of Taylor & Francis, an informa company.

This Is A New Release Of The Original 1910 Edition.

Child assent is recommended in addition to parental consent when enrolling children in clinical research; however, appreciation and relevance ascribed to these concepts vary in different contexts, and information on attitudes towards storage of biological samples for future research is limited, especially in developing countries. We assessed caregivers’ understanding and appreciation of consent and assent procedures, and their attitudes towards use of stored blood samples for future research prior to enrolling a child in clinical research. A total of 17 in-depth (...) interviews were conducted with primary caregivers of children at enrolment or on the immediate follow-up date. All caregivers recalled significant amount information from the study information sheet and were able to appropriately link such information to the consent process. While all participants confirmed information received prior to blood sampling as adequate, a few noted that the purpose was not sufficiently well communicated. Caregivers felt children were cognitively vulnerable, and prone to decisions that were not necessarily in their best interest. Nearly all caregivers felt it was their right and responsibility to overrule objections from their ward’s regarding enrolment into specific study or receipt of a therapeutic procedure. There were no objections or concerns regarding use of stored biological samples for future research purposes. There is thus, a need to improve understanding of caregivers on the information provided during the informed consent process. Context-specific studies on the age of assent in specific populations are needed. (shrink)

Dr. Ainslie examines an elementary human paradox: that we are endangered by our own wishes.

In this article we attend to recent critiques of psychometric applications of life history theory to variance among humans and develop theory to advance the study of latent LH constructs. We then reanalyze data previously examined by Richardson et al., 2017, https://doi.org/10.1177/1474704916666840 to determine whether previously reported evidence of multidimensionality is robust to the modeling approach employed and the structure of LH indicators is invariant by sex. Findings provide further evidence that a single LH dimension is implausible and that researchers (...) should cease interpreting K-factor scores as empirical proxies for LH speed. In contrast to the original study, we detected a small inverse correlation between mating competition and Super-K that is consistent with a trade-off. Tests of measurement invariance across the sexes revealed evidence of metric invariance, consistent with the theory that K is a proximate cause of its indicators; however, evidence of partial scalar invariance suggests use of scores likely introduces bias when the sexes are compared. We discuss limitations and identify approaches that researchers may use to further evaluate the validity of the K-factor and other applications of LH to human variation. (shrink)