Calpains are a family of calcium‐dependent thiol‐proteases which are proposed to be involved in many physiological processes as well as pathological conditions. Calpains are likely to be involved in processing of numerous enzymes and cytoskeletal components, thereby linking their activity to a variety of intracellular events. Although widely studied, the precise mechanism(s) involved in calpain activation and activity in vivo remain poorly understood. Initial studies suggested that calpain exists primarily as an inactive proenzyme that required autolytic cleavage for activation. It (...) was also hypothesized that calpain associated with membrane phospholipids, serving to increase calcium sensitivity, facilitating autolytic conversion and thus activating the enzyme. These hypotheses, however, have not been universally accepted and there is increasing evidence that intact, non‐autolyzed calpain is the physiologically active calpain form. (shrink)

The plays written about AIDS in the past dozen years form a radical canon establishing gay men as the locus for public attention. These plays have been all but silent in their representation of women with AIDS. This article examines the marginalized women in early plays such as The Normal Heart and As Is, and the women more central to later plays such as The Baltimore Waltz, Before It Hits Home, and Patient A. It foregrounds some of the most problematic (...) issues surrounding the AIDS virus: the perception of women as vectors of disease for men and unborn children, the insistent representation of women as mothers and caregivers, and the denial of patterns of abuse, sexual exploitation, and poverty which contribute to the marginalization of woman and people of color. (shrink)

Popper and Eccles present two different notions of Interactionism. Popper's arguments arise out of the traditional philosophical debate, whereas Eccles' arguments arise out of a mixture of neurophysiology and personal belief. Popper's three-world ontology is the philosophical foundation of both their positions. However, it is precisely against the background of the three Worlds that the considerable differences between their positions are apparent. Despite these defects, Interactionism is a productive notion since it does not place the Self beyond experimental investigation. Indeed, (...) both Popper and Eccles have made implicit suggestions as to experimental procedure which might contribute to the investigation of the Self. (shrink)

Popper and Eccles present two different notions of Interactionism. Popper's arguments arise out of the traditional philosophical debate, whereas Eccles' arguments arise out of a mixture of neurophysiology and personal belief. Popper's three-world ontology is the philosophical foundation of both their positions. However, it is precisely against the background of the three Worlds that the considerable differences between their positions are apparent. Despite these defects, Interactionism is a productive notion since it does not place the Self beyond experimental investigation. Indeed, (...) both Popper and Eccles have made implicit suggestions as to experimental procedure which might contribute to the investigation of the Self. (shrink)

The challenge that confronts corporate decision-makers in connection with global labor conditions is often in identifying the standardsby which they should govern themselves. In an effort to provide greater direction in the face of possible global cultural conflicts, ethicistsThomas Donaldson and Thomas Dunfee draw on social contract theory to develop a method for identifying basic human rights: Integrated Social Contract Theory (ISCT). In this paper, we apply ISCT to the challenge of global labor standards, attempting to identify labor rights that (...) could serve as guides for corporations producing or outsourcing outside of their home country. In addition to identifying areas of universal agreement, we also examine whether ISCT is, in fact, a sufficient basis for determining worker rights; we seek to define the parameters of the “sweatshop” problem; we include the application and results of our ISCT analysis as applied to labor standards: the global labor rights hypernorms; and conclude that ISCT is sufficient only for rights that are universal. We also discuss whether market-driven decisions can identify the boundaries of labor rights, or at least assure that market outcomes are compatible with maintaining labor rights, in order to respond to the shortcomings of ISCT. We conclude with some comments on directions of analysis for labor rights determination. (shrink)

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

We describe new results in parametrized complexity theory. In particular, we prove a number of concrete hardness results for W[P], the top level of the hardness hierarchy introduced by Downey and Fellows in a series of earlier papers. We also study the parametrized complexity of analogues of PSPACE via certain natural problems concerning k-move games. Finally, we examine several aspects of the structural complexity of W [P] and related classes. For instance, we show that W[P] can be characterized in terms (...) of the DTIME ) and NP. (shrink)

We study completely decomposable torsion-free abelian groups of the form $\mathcal{G}_S := \oplus_{n \in S} \mathbb{Q}_{p_n}$ for sets $S \subseteq \omega$. We show that $\mathcal{G}_S$has a decidable copy if and only if S is $\Sigma^0_2$and has a computable copy if and only if S is $\Sigma^0_3$.

This work contributes to the program of studying effective versions of “almost-everywhere” theorems in analysis and ergodic theory via algorithmic randomness. Consider the setting of Cantor space {0,1}N with the uniform measure and the usual shift. We determine the level of randomness needed for a point so that multiple recurrence in the sense of Furstenberg into effectively closed sets P of positive measure holds for iterations starting at the point. This means that for each k∈N there is an n such (...) that n,2n,…,kn shifts of the point all end up in P. We consider multiple recurrence into closed sets that possess various degrees of effectiveness: clopen, Π10 with computable measure, and Π10. The notions of Kurtz, Schnorr, and Martin-Löf randomness, respectively, turn out to be sufficient. We obtain similar results for multiple recurrence with respect to the k commuting shift operators on {0,1}Nk. (shrink)

Perhaps it is a measure of the controversy that Popper has evoked that this should be the first two-volume addition to Schilpp’s library. Certainly the thirty-three discursive and critical essays emanate from a galaxy of philosophical and other stars: Kraft, Kneale, Quine, Putnam, Lakatos, Medawar, Maxwell, Levison, Bar-Hillel, Eccles, Watkins, Campbell, Freeman & Skolimowski, Feigl & Meehl, Musgrave, Bernays, Bronowski, Lejewski, Schlesinger, Ayer, Agassi, Settle, Margenau, Suppes, Grünbaum, Kuhn, Wisdom, Boyle, Wild, Acton, Winch, Donagan, and Gombrich. The LLP faces (...) a problem, given that it takes a long time to mature a significant philosopher, for the project always teeters on the brink of human mortality; indeed, quite a few of the above contributors themselves are now defunct. It is therefore a pleasure to have a volume devoted to a philosopher whose work is very much alive, as is evidenced by the recent publication of Popper’s works on quantum theory and the Postscript to his Logic of Scientific Discovery. Moreover these volumes bring into salience the fundamental value of this style of publication that centers on written intellectual debate. Intellectuals in modern culture, especially in the United States, are sadly dispersed—there is not an abundance of discussion groups—so it is volumes like these that allow the isolate the linkages to sustained erudite exploration. So fruitful is this style of publication, that we find it emulated recently in such journals as Current Anthropology and The Brain and Behavioral Sciences. At least on paper, philosophical debate and exploration need not involve personal antipathy. Here, on the contrary, in the focusing on crucial issues, is the opportunity for personal sympathy and the struggle for mutual understanding. For methodological reasons centered on his concept of rationality, Popper has actively sought out intellectual controversy and these two volumes are therefore his natural milieu. Yet Popper has expressed a reluctance to write quickly and perhaps this explains why these volumes were a long time in the making. Certainly some of the papers such as Putnam’s “The ‘Corroboration’ of Theories” and Campbell’s “Evolutionary Epistemology” have had wide currency for some time now. But much that is good in these two volumes remains to be recognized, not the least of which is Popper’s “Intellectual Autobiography.” These 181 pages give the reader an inspiring impression of an intellect struggling after truth. Since Popper’s work has spanned the intellectual currents of the twentieth century and, in fact, dominated some of them, it would be difficult for this autobiography to fail. Popper’s writing has always struck this reviewer as an embodiment of Bacon’s maxim that truth will emerge more readily from error than from confusion, for he strives after simplicity and clarity in his writing with the consequence that disagreement is more closely focused. In this, he has lived out his central concept of critical rationality. At a more mundane level, there are all-too-human moments recorded, such as Popper’s reception at Oxbridge. Besides some enjoyable anecdotes, there is a little gentle self-mockery too. (shrink)

Cenzer, D., R. Downey, C. Jockusch and R.A. Shore, Countable thin Π01 classes, Annals of Pure and Applied Logic 59 79–139. A Π01 class P {0, 1}ω is thin if every Π01 subclass of P is the intersection of P with some clopen set. Countable thin Π01 classes are constructed having arbitrary recursive Cantor- Bendixson rank. A thin Π01 class P is constructed with a unique nonisolated point A and furthermore A is of degree 0’. It is shown that no (...) set of degree ≥0” can be a member of any thin Π01 class. An r.e. degree d is constructed such that no set of degree d can be a member of any thin Π01 class. It is also shown that between any two distinct comparable r.e. degrees, there is a degree that contains a set which is of rank one in some thin Π01 class. It is shown that no maximal set can have rank one in any Π01 class, while there exist maximal sets of rank 2. The connection between Π01 classes, propositional theories and recursive Boolean algebras is explored, producing several corollaries to the results on Π01 classes. For example, call a recursive Boolean algebra thin if it has no proper nonprincipal recursive ideals. Then no thin recursive Boolean algebra can have a maximal ideal of degree ≥0”. (shrink)

We develop a theory of LOGSPACE structures and apply it to construct a number of examples of Abelian Groups which have LOGSPACE presentations. We show that all computable torsion Abelian groups have LOGSPACE presentations and we show that the groups ${\mathbb {Z}, Z(p^{\infty})}$ , and the additive group of the rationals have LOGSPACE presentations over a standard universe such as the tally representation and the binary representation of the natural numbers. We also study the effective categoricity of such groups. For (...) example, we give conditions are given under which two isomorphic LOGSPACE structures will have a linear space isomorphism. (shrink)

Many natural computational problems have input consisting of two or more parts, one of which may be considered a parameter. For example, there are many problems for which the input consists of a graph and a positive integer. A number of results are presented concerning parameterized problems that can be solved in complexity classes below P, given a single word of advice for each parameter value. Different ways in which the word of advice can be employed are considered, and it (...) is shown that the class FPT of tractable parameterized problems has interesting and natural internal structure. (shrink)

Isaiah Berlin, 1909-1997 John Edward Christopher Hill, 1912-2003 Rodney Howard Hilton, 1916-2002 Morris Keith Hopkins, 1934-2004 Thomas Peter Ruffell Laslett, 1915-2001 Geoffrey Marshall, 1929-2003 John Smith Roskell, 1913-1998 Isaac Schapera, 1905-2003 Judah Benzion Segal, 1912-2003 John Cyril Smith, 1922-2003 Richard Arthur Wollheim, 1923-2003.

Artificial intelligence research has foundered on the issue of representation. When intelligence is approached in an incremental manner, with strict reliance on interfacing to the real world through perception and action, reliance on representation disappears. In this paper we outline our approach to incrementally building complete intelligent Creatures. The fundamental decomposition of the intelligent system is not into independent information processing units which must interface with each other via representations. Instead, the intelligent system is decomposed into independent and parallel activity (...) producers which all interface directly to the world through perception and action, rather than interface to each other particularly much. The notions of central and peripheral systems evaporateeverything is both central and peripheral. Based on these principles we have built a very successful series of mobile robots which operate without supervision as Creatures in standard office environments. (shrink)

The emergence of private authority has become a feature of the post-Cold War world. The contributors to this volume examine the implications of this erosion of the power of the state for global governance. They analyse actors as diverse as financial institutions, multinational corporations, religious terrorists and organised criminals. The themes of the book relate directly to debates concerning globalization and the role of international law, and will be of interest to scholars and students of international relations, politics, sociology and (...) law. (shrink)

Difficult Atheism shows how contemporary French philosophy is rethinking the legacy of the death of God in ways that take the debate beyond the narrow confines of atheism into the much broader domain of post-theological thinking. Christopher Watkin argues that Alain Badiou, Jean-Luc Nancy and Quentin Meillassoux each elaborate a distinctive approach to the post-theological, but that each approach still struggles to do justice to the death of God.