Calpain (Cp) is a calcium (Ca2+)‐dependent cysteine protease. Activation of the major isoforms of Cp, CpI and CpII, are required for a number of important cellular processes including adherence, shape change and migration. The current concept that cytoplasmic Cp locates and associates with its regulatory subunit (Rs) and substrates as well as translocates throughout the cell via random diffusion is not compatible with the spatial and temporal constraints of cellular metabolism. The novel finding that Cp and Rs function relies upon (...) tenacious hydrophobic interactions with organelle membranes offers a unifying explanation for the paradoxical and puzzling features of Cp activation and regulation such as how nM concentrations of intracellular Ca2+ can activate Cp molecules requiring μM to mM concentrations of Ca2+ for in vitro activation, and how this protease can spatially and temporally locate specific substrates and translocate throughout the cell. We hypothesize that Cp and its regulatory moieties associate with organelles to facilitate the activation of this protease resulting in the cleavage of substrates and aid in its translocation throughout the cell. BioEssays 28: 850–859, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Im folgenden sollen zwei Arbeiten zur theoretischen Mathematik vorgestellt werden, die im 14. Jahrhundert entstanden. Die eine stammt von Thomas Bradwardine (um 1290 - 1349), einem der wichtigsten Mathematiker dieser Zeit, die andere von dem praktisch unbekannten Wigandus Durnheimer. Bei Bradwardine soll insbesondere die Frage beantwortet werden, welche der arithmetischen Schriften, die ihm zugeschrieben werden, wirklich von ihm stammt. Bei Durnheimers Schrift, einer Kompilation, die u.a. auf Bradwardines Abhandlung beruht, werden der Inhalt der einzelnen Kapitel und deren Quellen angegeben.

Social media applications such as Twitter, YouTube and Facebook have attained huge popularity, with more than three billion people and organizations predicted to have a social networking account by 2015. Social media offers a rapid avenue of communication with the public and has potential benefits for communicable disease control and surveillance. However, its application in everyday public health practice raises a number of important issues around confidentiality and autonomy. We report here a case from local level health protection where the (...) friend of an individual with meningococcal septicaemia used a social networking site to notify potential contacts. (shrink)

BackgroundDespite rapid growth of the scientific literature, no consensus guidelines have emerged to define the optimal criteria for editors to grade submitted manuscripts. The purpose of this project was to assess the peer reviewer metrics currently used in the surgical literature to evaluate original manuscript submissions.MethodsManuscript grading forms for 14 of the highest circulation general surgery-related journals were evaluated for content, including the type and number of quantitative and qualitative questions asked of peer reviewers. Reviewer grading forms for the seven (...) surgical journals with the higher impact factors were compared to the seven surgical journals with lower impact factors using Fisher’s exact tests.ResultsImpact factors of the studied journals ranged from 1.73 to 8.57, with a median impact factor of 4.26 in the higher group and 2.81 in the lower group. The content of the grading forms was found to vary considerably. Relatively few journals asked reviewers to grade specific components of a manuscript. Higher impact factor journal manuscript grading forms more frequently addressed statistical analysis, ethical considerations, and conflict of interest. In contrast, lower impact factor journals more commonly requested reviewers to make qualitative assessments of novelty/originality, scientific validity, and scientific importance.ConclusionSubstantial variation exists in the grading criteria used to evaluate original manuscripts submitted to the surgical literature for peer review, with differential emphasis placed on certain criteria correlated to journal impact factors. (shrink)

The volume brings together a collection of original papers on some of the main tenets of Joseph Raz's legal and political philosophy: Legal positivism and the nature of law, practical reason, authority, the value of equality, incommensurability, harm, group rights, and multiculturalism. James Griffin and Yael Tamir raise questions concerning Raz's notion of group rights and its application to claims of cultural and political autonomy, while Will Kymlicka and Bernhard Peters examine Raz's theory of multicultural society. Lukas Meyer investigates the (...) applicability of the notion of harm in the intergenerational context. Other papers are devoted to fundamental theoretical tenets of Raz's work. Hillel Steiner and Andrei Marmor examine Raz's account of value pluralism and incommensurability in light of what these authors consider to be goods whose equal distribution must be valued for its own sake. Robert Alexy and Timothy Endicott discuss traditional issues of jurisprudence and legal philosphy with special attention to Raz's contribution. Rüdiger Bittner, Bruno Celano, and J. E. Penner discuss and criticize aspects of Raz's theory of practical reason. Jeremy Waldron presents a critique of Raz's interpretation of authority.This volume concludes with a chapter by Joseph Raz in which he responds to arguments in the foregoing essays. (shrink)

Many adoptees face a number of challenges relating to separation from biological parents during the adoption process, including issues concerning identity, intimacy, attachment, and trust, as well as language and other cultural challenges. One common health challenge faced by adoptees involves lack of access to genetic-relative family health history. Lack of GRFHx represents a disadvantage due to a reduced capacity to identify diseases and recommend appropriate screening for conditions for which the adopted person may be at increased risk. In this (...) article, we draw out common features of traditionally understood “health disparities” in order to identify analogous features in the context of adoptees’ lack of GRFHx. (shrink)

Où se trouve le sérieux? L'auteur se pose cette question peu commune, et se met en quête d'une réponse. Il propose une articulation du sérieux selon les modes épistémologique, esthétique et éthique, pour l'approcher indirectement par le feint, le comique et le léger. Il s'attaque d'abord au problème que pose une quête du sérieux par le " feint ", ce qui le conduit à des interprétations originales du doute cartésien, du langage philosophique et de la connaissance scientifique : il distingue (...) le feint du fictif et du faux, mais constate aussi que le feint a tendance à se transformer en l'un ou en l'autre. L'auteur s'aventure ensuite dans le domaine esthétique où, à partir d'une critique de la théorie bergsonienne du rire, il développe sa propre interprétation du comique ; il soutient que la musique est l'art relativement le plus sérieux, mais que le sérieux comme tel est absent de l'art. Passant à la morale, il se voit obligé d'abord de s'expliquer avec les existentialistes français, ennemis déclarés du sérieux, puis, après une franche appréciation du sérieux de notre époque, d'admettre finalement que le léger y joue un rôle essentiel aussi. Distinguant en plus le sérieux du fanatique, l'auteur tente de préciser les rapports entre le sérieux et la foi, la Bible, et la pensée kierkegaardienne. Il conclut que la philosophie, et plus particulièrement la métaphysique, est le ressort du sérieux, mais que le philosophe est tenu par son sérieux même de chercher toujours plus loin. Le livre est écrit sous la forme de carnets, dans un style clair et engageant ; non dépourvu d'humour, il s'adresse à tout lecteur philosophiquement averti. (shrink)

This paper argues that it will be important for new genomic technologies to recognize the limits of traditional approaches to informed consent, so that other-regarding implications of genomic information can be properly contextualized and individual rights respected. Respect for individual autonomy will increasingly require dynamic consideration of the interrelated dimensions of individual and broader community interests, so that the interests of one do not undermine fundamental interests of the other. In this, protection of individual rights will be a complex interplay (...) between individual and community concerns. (shrink)

This article won the Mind prize essay competition announced last year, for an essay defending the academic pursuit of philosophy. The author is at present a free-lance philosopher; at the time of writing the paper he was a part time lecturer at the University of Newcastle upon Tyne, in the department that has since closed. His collection of aphorisms, Sentences and Slogans has recently been published privately (for details, see 'Books Received').

There are doubtless many with personal experience of suffering, or of comforting others in distress, who would agree with Milton thus far that philosophic argument is powerless to satisfy those who in their anguish ask the question ‘Why did it happen to me?’ Yet to think so is to underestimate both the necessity and the power of reason: clarity of mind and the disposition to argue are commonly enhanced rather than diminished by suffering; and if reason is an essential part (...) of man's nature, it should serve him, if anywhere, in the trials of life. We have every justification, therefore, despite common opinion, for seeking a rational answer to the question proposed. It must, however, be admitted at the outset that there is no direct answer to the question which can both withstand critical scrutiny and bring genuine comfort to the afflicted, an answer, that is, which accepts the question as it stands with its attendant presuppositions; but there is an indirect answer, which, precisely by rejecting one or more of these presuppositions and restating the question, can indeed satisfy these two requirements. Before such an answer can be outlined, however, the question in its traditional form must be examined and the traditional answers to it critically reviewed. (shrink)

Amongst Kant's lesser known early writings is a short treatise with the curious title Dreams of a Spirit-Seer Explained by Dreams of Metaphysics, in which, with considerable acumen and brilliance, and not a little irony, Kant exposes the empty pretensions of his contemporary, the Swedish visionary and Biblical exegete, Emanuel Swedenborg, to have access to a spirit world, denied other mortals. Despite his efforts, it must be feared, however, that Kant did not, alas, succeed in laying the spirit of Swedenborg (...) himself to rest once and for all, for there has arisen in our own day, and within philosophy itself, a movement of thought, if such it can be called, which, like that of Swedenborg, is founded upon an unbridled and unhealthy exercise of the imagination, and apparently believes that philosophical problems can be discussed and resolved by the elaboration of fantastical, and at times repulsive, examples; if we require a name for this contemporary pretence at philosophy, we could take as our model the Italian word for science fiction, fantascienza, and call it ‘fantaphilosophy’: it is my aim to show that this fantaphilosophy is a phantom philosophy. (shrink)

Traditional approaches to measurement of violations of academic integrity may overestimate the magnitude and severity of cheating and confound panic with planned cheating. Differences in the severity and level of premeditation of academic integrity violations have largely been unexamined. Results of a study based on a combined sample of business students showed that students are more likely to commit minor cheating offenses and engage in panic-based cheating as compared to serious and planned cheating offenses. Results also indicated there is a (...) significant interaction between severity and type of cheating. We hypothesized serious and planned cheating offenses would be related to justifications and found the largest differences were between panic and planned. Finally, panic and minor cheating were associated with two self-control-related personality traits. Implications for cheating research are discussed. (shrink)

Academic misconduct is widespread in schools, colleges, and universities and it appears to be an international phenomenon that also spills over into the workplace. To this end, while a great deal of research has investigated various individual components such as, demographic, personality and situational factors that contribute to cheating, research has yet to examine why students help others cheat and which students are being asked to help others cheat. In this study, we investigated if the closeness of the relationship to (...) the individual requesting help in cheating to the individual being asked to help cheat, influenced the decision to help cheat. We also investigated if past cheating behavior predicted how an individual would respond to requests to cheat. Additionally, we sought to answer the following questions; whether minor cheating is more prevalent than serious cheating, what personality factors predict helping others cheat, who is helped, and how people rationalize helping others cheat. Results indicate minor cheating to be more prevalent, prudent personalities are less likely to have cheated or to help others cheat, individuals are more likely to help friends cheat than to help strangers, and past cheating behaviors is indicative of helping others to cheat. Implications for research and practice are discussed. (shrink)

Recent, well-publicized scandals, involving unethical conduct have rekindled interest in academic misconduct. Prior studies of academic misconduct have focussed exclusively on situational factors (e.g., integrity culture, honor codes), demographic variables or personality constructs. We contend that it is important to also examine how␣these classes of variables interact to influence perceptions of and intentions relating to academic misconduct. In a sample of 217 business students, we examined how integrity culture interacts with Prudence and Adjustment to explain variance in estimated frequency of (...) cheating, suspicions of cheating, considering cheating and reporting cheating. Age, integrity culture, and personality variables were significantly related to different criteria. Overall, personality variables explained the most unique variance in academic misconduct, and Adjustment interacted with integrity culture, such that integrity culture had more influence on intentions to cheat for less well-adjusted individuals. Implications for practice are discussed and future research directions are offered. (shrink)

We present a series of three analyses of young children's linguistic input to determine the distributional information it could plausibly offer to the process of grammatical category learning. Each analysis was conducted on four separate corpora from the CHILDES database (MacWhinney, 2000) of speech directed to children under 2;5. We showthat, in accord with other findings, a distributional analysis which categorizeswords based on their co‐occurrence patterns with surroundingwords successfully categorizes the majority of nouns and verbs. In Analyses 2 and 3, (...) we attempt to make our analyses more closely relevant to natural language acquisition by adopting more realistic assumptions about howyoung children represent their input. In Analysis 2, we limit the distributional context by imposing phrase structure boundaries, and find that categorization improves even beyond that obtained from less limited contexts. In Analysis 3, we reduce the representation of input elements which young children might not fully process and we find that categorization is not adversely affected: Although noun categorization is worse than in Analyses 1 and 2, it is still good; and verb categorization actually improves. Overall, successful categorization of nouns and verbs is maintained across all analyses. These results provide promising support for theories of grammatical category formation involving distributional analysis, as long as these analyses are combined with appropriate assumptions about the child learner's computational biases and capabilities. (shrink)