Intercellular communication is an essential process in all multicellular organisms. During this process, molecules secreted by one cell will bind to a receptor on the cognate cell leading to the subsequent uptake of the receptor‐ligand complex. Once inside, the cell then determines the fate of the receptor‐ligand complex and any other proteins that were endocytosed together. Approximately 80% of endocytosed material is recycled back to the plasma membrane either directly or indirectly via the Golgi apparatus and the remaining 20% is (...) delivered to the lysosome for degradation. Although most pathways have been identified, we still lack understanding on how specificity in sorting of recycling cargos into different pathways is achieved, and how the cell reaches high accuracy of these processes in the absence of clear sorting signals in the bulk of the client proteins. In this review, we will summarize our current understanding of the mechanism behind recycling cargo sorting and propose a model of differential affinities between cargo and cargo receptors/adaptors with regards to iterative sorting in endosomes. (shrink)

Metamemory processes depend on different factors across the learning and memory time-scale. In the laboratory, subjects are often asked to make prospective feeling-of-knowing (FOK) judgments about target retrievability, or are asked to make retrospective confidence judgments (RCJs) about the retrieved target. We examined distinct and shared contributors to metamemory judgments, and how they were built over time. Eye movements were monitored during a face-scene associative memory task. At test, participants viewed a studied scene, then rated their FOK that they would (...) remember the associated face. This was followed by a forced choice recognition test and RCJs. FOK judgments were less accurate than RCJ judgments, showing that the addition of mnemonic experience can increase metacognitive accuracy over time. However, there was also evidence that the given FOK rating influenced RCJs. Turning to eye movements, initial analyses showed that higher cue fluency was related to both higher FOKs and higher RCJs. However, further analyses revealed that the effects of the scene cue on RCJs were mediated by FOKs. Turning to the target, increased viewing time and faster viewing of the correct associate related to higher FOKs, consistent with the idea that target accessibility is a basis of FOKs. In contrast, the amount of viewing directed to the chosen face, regardless of whether it was correct, predicted higher RCJs, suggesting that choice experience is a significant contributor RCJs. We also examined covariates of the change in RCJ rating from the FOK rating, and showed that increased and faster viewing of the chosen face predicted raising one’s confidence above one’s FOK. Taken together these results suggest that metamemory judgments should not be thought of only as distinct subjective experiences, but complex processes that interact and evolve as new psychological bases for subjective experience become available. (shrink)

_Telling Stories to Change the World_ is a powerful collection of essays about community-based and interest-based projects where storytelling is used as a strategy for speaking out for justice. Contributors from locations across the globe—including Uganda, Darfur, China, Afghanistan, South Africa, New Orleans, and Chicago—describe grassroots projects in which communities use narrative as a way of exploring what a more just society might look like and what civic engagement means. These compelling accounts of resistance, hope, and vision showcase the power (...) of the storytelling form to generate critique and collective action. Together, these projects demonstrate the contemporary power of stories to stimulate engagement, active citizenship, the pride of identity, and the humility of human connectedness. (shrink)

A. W. Moore argues in this bold and unusual book that it is possible to think about the world from no point of view. His argument involves discussion of a very wide range of fundamental philosophical issues, including the nature of persons, the subject-matter of mathematics, realism and anti-realism, value, the inexpressible, and God. The result is a powerful critique of our own finitude. 'imaginative, original, and ambitious' Robert Brandom, Times Literary Supplement.

A structure which generalizes formulas by including substitution terms is used to represent proofs in classical logic. These structures, called expansion trees, can be most easily understood as describing a tautologous substitution instance of a theorem. They also provide a computationally useful representation of classical proofs as first-class values. As values they are compact and can easily be manipulated and transformed. For example, we present an explicit transformations between expansion tree proofs and cut-free sequential proofs. A theorem prover which represents (...) proofs using expansion trees can use this transformation to present its proofs in more human-readable form. Also a very simple computation on expansion trees can transform them into Craig-style linear reasoning and into interpolants when they exist. We have chosen a sublogic of the Simple Theory of Types for our classical logic because it elegantly represents substitutions at all finite types through the use of the typed -calculus. Since all the proof-theoretic results we shall study depend heavily on properties of substitutions, using this logic has allowed us to strengthen and extend prior results: we are able to prove a strengthen form of the firstorder interpolation theorem as well as provide a correct description of Skolem functions and the Herbrand Universe. The latter are not straightforward generalization of their first-order definitions. (shrink)

We examine the notion of inquiry and argue that philosophic inquiry is a transcendental activity. Activities, viewed as conforming to intelligible canons, applying to appropriate contexts, and directed to specifiable ends, are contrasted with their empirical descriptions. Inquiry, characterized as an internalized, continuous activity directed to an intrinsic end, and fundamentally presupposed by other activities, is considered at the levels of (1) science, (2) philosophy and (3) transcendental philosophy. We argue that (2) is a transcendental activity which determines non-empirical concepts (...) and is presupposed by (1). Alternative philosophic frameworks are grounded on hypothetical canons conceived by intelligence itself, which imply interpretations of objectivity and universality claiming validity for the community of inquirers, but they can always be rejected. We consider the possibility of categorical canons operating as second-order rules necessarily presupposed for the formulation of alternative philosophic frameworks, and (3) would be the activity of identifying, justifying and applying such transcendental canons of inquiry in general. Finally, we suggest that the only possible justification of such categorical canons would be a kind of ontological proof. Thus, a given philosophic approach reflects the transcendental activity of determining non-empirical concepts through the implementation of its fundamental regulative norms; but transcendental philosophy would determine the concept of philosophy itself through implementation of the categorical canons of inquiry in the construction of philosophic systems. (shrink)

I suppose the most obvious difference in fact between dreams and waking life is the chaotic nature of the former. But this somehow seems to be a mere contingency. Some of our dreams are more contingent than others, and it seems hard to impose any upper limit of coherence on them. Also it is usually after we wake up that they seem incoherent. Similarly many dreams are largely matters of sensation and emotion, mood and atmosphere, with little or no reasoning (...) in them; but this again is contingent, and dreams vary; Professor Broad, 56-57) relates a quite detailed scientific experiment which he carried out in a dream. (shrink)

Different approaches have been proposed in order to achieve knowledge integration for coronary care monitoring applications, usually in the form of expert systems. The clinical impact of these expert systems, which are based only on "shallow" knowledge, has not been remarkable due to the difficulties associated with the construction and maintenance of a complete knowledge base. Model-based systems represent an alternative to these problems because they allow efficient integration of the "deep" knowledge on the underlying physiological phenomena being monitored. In (...) this work, a brief review of existing model-based systems for cardiac rhythm interpretation is presented, followed by the description of a new system forCardiac Arrhythmia Recognition by Model-Based ECG Matching (CARMEM). Fundamental characteristics of CARMEM are presented; in particular, its ability to provide on-line parameter adaptation to simulate complex rhythms and to match observed ECG signals. The proposed model can be useful for the explanation of the origin of cardiac arrhythmias and contribute towards their robust characterization in the context of coronary care units. (shrink)

Книга рассчитана на тех, кто по своей специальности занимается философией, литературоведением и в дальнейшем углубят свои знания в этом вопросе, а также для широкого круга читателей.

The physician charter on medical professionalism creates standards of ethical behaviour for physicians and has been endorsed by professional organisations worldwide. It is based on the cardinal principles of the primacy of patient welfare, patient autonomy, and social welfare. There has been little discussion in the bioethics community of the doctrine of the charter and none from a Jewish ethical perspective. In this essay the authors discuss the obligations of the charter from a Jewish ethical viewpoint and call on other (...) cultures to develop their own unique perspectives on this important document. (shrink)

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