The cyclic opeptide Cyclosporinee A (CsA) is best known as the immunosuppressive drug which has revoulutionized organ transplantation. It selectively suppresses T cell activation by blocking the transcription of cytokine genes such as IL‐2 at the level of transxcription factor modulation. The structurally unrelated immuniusuppressant FK 506 acts on the same pathway and blocks cytokine gene expression. In contrast, rapamycin, a structural analoguwe of FK 506, interferes with the immune response at a different level, by blocking the response induced by (...) ctytokines such as IL‐2.Although these drugs have been most studied for their immunosuppressive activities, it is clear that their effects on cytokine pathways extend far beyond the scole IL‐2.‐mediated responses involved in the immune response. IFor instance, CsA and FK 506 inhibit the transcription of IL‐3, IL‐4, IFNγ, TNFα or GM‐CSF by activated T cells, and rapamycin has been shown to blcock the response to various growth factors such as IL‐3, IL‐4 or IL‐6.Here, we receap what is known about the effects of CsA, FK 506 and rapamycin on hematopoiesis in vitro and in vivo and extrapolate on what these drugs can teach us aboput the physiological role of cytokines for hematopoiesis. (shrink)

Gilead et al. offer a thoughtful and much-needed treatment of abstraction. However, it fails to build on an extensive literature on abstraction, representational diversity, neurocognition, and psychopathology that provides important constraints and alternative evidence-based conceptions. We draw on conceptions in software engineering, socio-technical systems engineering, and a neurocognitive theory with abstract representations of gist at its core, fuzzy-trace theory.

Evidence favors the nested sets hypothesis, introduced by fuzzy-trace theory (FTT) in the 1990s to explain effects and extended to many tasks, including conjunction fallacy, syllogistic reasoning, and base-rate effects (e.g., Brainerd & Reyna 1990; Reyna 1991; 2004; Reyna & Adam 2003; Reyna & Brainerd 1995). Crucial differences in mechanisms distinguish the FTT and Barbey & Sloman (B&S) accounts, but both contrast with frequency predictions (see Reyna & Brainerd, in press).

Although Stanovich & West (S&W) are likely to be criticized for not proposing a process model, results of such a model (fuzzy-trace theory) support many of their conclusions. However, arguments concerning evolution and Gricean intelligence are weak. Finally, developmental data are relevant to rationality, but contradictory results suggest a dual-processes approach that differs from S&W's based on fuzzy-trace theory.

Neurobiologically informed integration of research on memory, emotion, and behavior change in psychotherapy is needed, which Lane at al. advance. Memory reconsolidation that incorporates new emotional experience plays an important role in therapeutic change, converging with evidence for Fuzzy Trace Theory. Applications of Fuzzy Trace Theory to Cognitive Behavioral Therapy (CBT) for youth at risk for psychosis, and to other aspects of behavior change, are discussed.

Current guidelines and regulatory frameworks create a dilemma that threatens the effectiveness of much needed communication between patients and medical providers: How can patients be presented with detailed facts without creating cognitive “overload”? We explain how this is a false dichotomy and illustrate, using three examples, how fuzzy-trace theory offers a third way of informing patients.

Although the Ca2+‐dependent proteinase (calpain) system has been found in every vertebrate cell that has been examined for its presence and has been detected in Drosophila and parasites, the physiological function(s) of this system remains unclear. Calpain activity has been associated with cleavages that alter regulation of various enzyme activities, with remodeling or disassembly of the cell cytoskeleton, and with cleavages of hormone receptors. The mechanism regulating activity of the calpain system in vivo also is unknown. It has been proposed (...) that binding of the calpains to phospholipid in a cell membrane lowers the Ca2+ concentration, [Ca2+], required for the calpains to autolyze, and that autolysis converts an inactive proenzyme into an active protease. Recent studies, however, show that the calpains bind to specific proteins and not to phospholipids, and that binding to cell membranes does not affect the [Ca2+] required for autolysis. It seems likely that calpain activity is regulated by binding of Ca2+ to specific sites on the calpain molecule, with binding to each site eliciting a response (proteolytic activity, calpastatin binding, etc.) specific for that site. Regulation must also involve an, as yet, undiscovered mechanism that increases the affinity of the Ca2+‐binding sites for Ca2+. (shrink)

Memory exhibits episodic superposition, an analog of the quantum superposition of physical states: Before a cue for a presented or unpresented item is administered on a memory test, the item has the simultaneous potential to occupy all members of a mutually exclusive set of episodic states, though it occupies only one of those states after the cue is administered. This phenomenon can be modeled with a nonadditive probability model called overdistribution (OD), which implements fuzzy-trace theory's distinction between verbatim and gist (...) representations. We show that it can also be modeled based on quantum probability theory. A quantum episodic memory (QEM) model is developed, which is derived from quantum probability theory but also implements the process conceptions of global matching memory models. OD and QEM have different strengths, and the current challenge is to identify contrasting empirical predictions that can be used to pit them against each other. (shrink)

Sugar, pork, beer, corn, cider, scrapple, and hoppin' John all became staples in the diet of colonial America. The ways Americans cultivated and prepared food and the values they attributed to it played an important role in shaping the identity of the newborn nation. In A Revolution in Eating, James E. McWilliams presents a colorful and spirited tour of culinary attitudes, tastes, and techniques throughout colonial America. Confronted by strange new animals, plants, and landscapes, settlers in the colonies and West (...) Indies found new ways to produce food. Integrating their British and European tastes with the demands and bounty of the rugged American environment, early Americans developed a range of regional cuisines. From the kitchen tables of typical Puritan families to Iroquois longhouses in the backcountry and slave kitchens on southern plantations, McWilliams portrays the grand variety and inventiveness that characterized colonial cuisine. As colonial America grew, so did its palate, as interactions among European settlers, Native Americans, and African slaves created new dishes and attitudes about food. McWilliams considers how Indian corn, once thought by the colonists as "fit for swine," became a fixture in the colonial diet. He also examines the ways in which African slaves influenced West Indian and American southern cuisine. While a mania for all things British was a unifying feature of eighteenth-century cuisine, the colonies discovered a national beverage in domestically brewed beer, which came to symbolize solidarity and loyalty to the patriotic cause in the Revolutionary era. The beer and alcohol industry also instigated unprecedented trade among the colonies and further integrated colonial habits and tastes. Victory in the American Revolution initiated a "culinary declaration of independence," prompting the antimonarchical habits of simplicity, frugality, and frontier ruggedness to define American cuisine. McWilliams demonstrates that this was a shift not so much in new ingredients or cooking methods, as in the way Americans imbued food and cuisine with values that continue to shape American attitudes to this day. (shrink)

Martin Heidegger is, perhaps, the most controversial philosopher of the twentieth-century. Little has been written on him or about his work and its significance for educational thought. This unique collection by a group of international scholars reexamines Heidegger's work and its legacy for educational thought.

The data produced by the scientific community impacts on academia, clinicians, and the general public; therefore, the scientific community and other regulatory bodies have been focussing on ethical codes of conduct. Despite the measures taken by several research councils, unethical research, publishing and/or reviewing behaviours still take place. This exploratory study considers some of the current unethical practices and the reasons behind them and explores the ways to discourage these within research and other professional disciplinary bodies. These interviews/discussions with PhD (...) students, technicians, and academics/principal investigators were conducted mostly in European higher education institutions including UK, Italy, Ireland, Portugal, Czech Republic and Netherlands.Through collegiate discussions, sharing experiences and by examining previously published/reported information, authors have identified several less reported behaviours. Some of these practices are mainly influenced either by the undue institutional expectations of research esteem or by changes in the journal review process. These malpractices can be divided in two categories relating to methodological malpractices including data management, and those that contravene publishing ethics. The former is mostly related to “committed bias”, by which the author selectively uses the data to suit their own hypothesis, methodological malpractice relates to selection of out-dated protocols that are not suited to the intended work. Although these are usually unintentional, incidences of intentional manipulations have been reported to authors of this study. For example, carrying out investigations without positive controls; but including these from a previous study. Other methodological malpractices include unfair repetitions to gain statistical significance, or retrospective ethical approvals. In contrast, the publication related malpractices such as authorship malpractices, ethical clearance irregularities have also been reported. The findings also suggest a globalised approach with clear punitive measures for offenders is needed to tackle this problem. (shrink)

We performed three experiments to investigate whether adjectives can modulate the sensorimotor activation elicited by nouns. In Experiment 1, nouns of graspable objects were used as stimuli. Participants had to decide if each noun referred to a natural or artifact, by performing either a precision or a power reach‐to‐grasp movement. Response grasp could be compatible or incompatible with the grasp typically used to manipulate the objects to which the nouns referred. The results revealed faster reaction times (RTs) in compatible than (...) in incompatible trials. In Experiment 2, the nouns were combined with adjectives expressing either disadvantageous information about object graspability (e.g., sharp) or information about object color (e.g., reddish). No difference in RTs between compatible and incompatible conditions was found when disadvantageous adjectives were used. Conversely, a compatibility effect occurred when color adjectives were combined with nouns referring to natural objects. Finally, in Experiment 3 the nouns were combined with adjectives expressing tactile or shape proprieties of the objects (e.g., long or smooth). Results revealed faster RTs in compatible than in incompatible condition for both noun categories. Taken together, our findings suggest that adjectives can shape the sensorimotor activation elicited by nouns of graspable objects, highlighting that language simulation goes beyond the single‐word level. (shrink)

The future of work is forcing the world to adjust to a new paradigm of working. New skills will be required to create and adopt new technology and working methods. Additionally, cognitive skills, particularly creative problem-solving, will be highly sought after. The future of work paradigm has threatened many occupations but bolstered others such as engineering. Engineers must keep up to date with the technological and cognitive demands brought on by the future of work. Using an exploratory mixed-methods approach, our (...) study sought to make sense of how engineers understand and use creative problem solving. We found significant associations between engineers’ implicit knowledge of creativity, exemplified creative problem solving, and the perceived value of creativity. We considered that the work environment is a potential facilitator of creative problem-solving. We used an innovative exceptional cases analysis and found that the highest functioning engineers in terms of knowledge, skills, and perceived value of creativity, also reported working in places that facilitate psychosocially safe environments to support creativity. We propose a new theoretical framework for a creative environment by integrating the Four Ps and psychosocial safety climate theory that management could apply to facilitate creative problem solving. Through the acquisition of knowledge to engage in creative problem solving as individuals or a team, a perception of value must be present to enforce the benefit of creativity to the engineering role. The future of work paradigm requires that organisations provide an environment, a psychosocially safe climate, for engineers to grow and hone their sought-after skills that artificial technologies cannot currently replace. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

The question of violence is the horizon of the degradation of the political on the police, which touches today on the most intimate questions, it is to thwart a symbolic peril which concerns language itself. But if this language of culture runs a risk, today, it is that of vacuity, which seems to be attested to by the order word of « zero tolerance » or the success c f the crime of « outrage ». Where the violence of the (...) protestor becomes intolerable, the violence of influence is multiplying. More banally, this vacuity reflects a defection of the real, constructed froth the incommensurable and meaningless but also from such words as difference or alterity. A becoming-woman of language reunited with the real, that of struggle but perhaps more accurately, that of daily resistance, of the slightest gestures which ensure that, in spite of everything, life remains. (shrink)

This paper examines the contribution of the PhD dissertation of the American cytologist Michael F. Guyer (1874-1959) to the early establishment (in 1902-1903) of the parallel relationship between cytological chromosome behaviour in meiosis and Mendel's laws. Guyer's suggestions were among the first, which attempted to relate the variation observed in the offspring in hybridisation studies by a coherent cytological chromosome mechanism to meiosis before the rediscovery of Mendel's principles. This suggested for the first time that the chromosome mechanism involved a (...) conjugation of maternal and paternal chromosomes during the synapsis followed by a segregation of parental chromosomes in the final germ cells and a random union of the final germ cells in the fertilization. It shows that this early suggestion was similar to William Austin Cannon's later chromosome proposal attempting to explain Mendel's principles and had some influence on Walter Sutton's cytological suggestion explaining correctly the behaviour of Mendel's particle by 1903. (shrink)

Richard Kraut’s intriguing and provocative book, The Quality of Life, offers a sustained defence of strong experientialism (perhaps also a surprising defence, f.

In his Explaining Behavior, Fred Dretske uses a reliabilist theory of representation to try to vindicate the use of intentional explanation for behaviour against latter-day elitninativism. Although Dretske's indicator semantics turns on the notion of function, he himself never explicitly defines what function means. Dretske's reticence in discussing function may ultimately be an error, for, as I argue, his implicit understanding of what a function amounts to does not fit with data from op rant conditioning. Still, this need not be (...) a deep flaw in Dretske and I offer one way in which we may patch up the notion of function via the changes known to occur with learning in the brain. Ultimately, I conclude that the only facts needed to explain behaviour are (1) the conditions in the world that are paired with neuronal circuit activation (as picked out by goals in some circumstances); and (2) what motor output that condition triggers. (shrink)

1. The most important aspect of touch is its relation to time and space, a relation which is established by the movement of touching itself. Referring to the ideas of E. Straus, the distinction between touching and being touched is elaborated in light of experiments done by us with animals. 2. Touching is: being in one's own limits and at the same time going beyond these limits, a situation in which the touched object is felt at the same time as (...) a "Gegenstand" and as "Mit-seiend." "Pour le tactile, c'est l'être à deux qui se place au premier rang" . The awareness of being by the sense of touch is particularly poignant in the case of touching oneself, which is an exceptional unity of the active and the passive state of mind. 3. The tactile recognition of form also presents a dialectic of activity and passivity, a dialectic which takes place in the form of a development which conquers time, and this after a scheme produced during the act of grasping itself. We refer to the studies of V. von Weizsäcker on the "Gestaltkreis." We must also remember the basic restlessness of the hand, which becomes lasting in the play of the hand with an object. 4. The hand can hold an object. In doing so a schematic tactile image is given, an image which functions as a hypothesis or as an organizing principle of the proleptic development of further tactile exploration. The phenomenological analysis of touch with the hand appears as a prefiguration of thought by synthetic judgments. Thus, it is true, as Herder remarked, and as Gold-stein and Merleau-Ponty confirmed, that perception by man and spiritual existence are identical. 5. Referring to the research of Révèsz and Palagyi, the real nature of the tactile world is anlyzed. Tactile exploration is done according to a real development, during which take place anticipatory and retrospective determinations which assure the continuity of the event and its meaning. Tactile perception permits description of the continuous unity of the discontinuous phases which we can state objectively "as if" expectation and memory, preliminary judgments and their checking, conceptual fixations and corrections had been put to work. 6. Important is the affective and emotional aspect of tactile impressions and their connection with inter-human relationships. 7. By touch, man establishes in a "feeling" way a personal relationship with the matter of things, which is hidden to the distance senses. This participation has a double aspect. It is like the birth of a "mood," of a "Befindlichkeit," but at the same time it is the active point of departure of a "feeling," of an "understanding," of an "inner grasp," of a being moved, of a being struck by the touched object which is then in our presence as a real "quale," as a material object, as a being in itself. We remember the proper nature of the caress, by which the "being together" of the caressed object complements that of the active caresser. The usual concepts by means of which, in practical and gnostic life, the most important tactile qualities are indicated intend to refer us to the characteristics of the things which take up space in the geometric world and in objectively measurable space, and on which is founded our natural orientation. We remember von Hornborstel's research on the intermodal characteristics of tactile impressions. These show us how a "knowledge" which accompanies perception can change an impression of feeling. The affective relationship, determined by a shaded "knowledge" and by a system of values, changes tangible reality, the substantiality of the body, of the "flesh." This affective change of matter, this "phenomenal transsubstantiation," easily becomes a reality in connection with objects of which we know that they belong or did belong to someone. The meaning which a thing has changes the matter of the object, an object which precisely by the touch is present "in the flesh." This is illustrated more precisely by the phenomena of fetishism, and by simple experiences of daily life. If we look for an anthropological point of view from which touch, of which the hand realizes the point of view will have to be attempted starting from the unimaginable certitude that the ontological unity of nature and spirit is in man the reality of a possible participation, a participation which, in our existence, is only indicated. The "restlessness" of the hand, never fulfilled and always searching, which we noted, is the human token of our concrete existence. Thus touch shows us what Valery remarked about the mind: "The mind is at the mercy of the body, as the blind are at the mercy of the seeing.". (shrink)

El presente artículo presenta los nuevos e importantes descubrimientos en la terraza litoral al pie del oasis de niebla, a partir de Noviembre de 2003, que junto a estudios anteriores conforman un cuadro general bastante completo de los patrones de asentamiento, modus vivendi, costumbres y actividades económicas de los antiguos pobladores costeros del norte de Chile, que reafirman la enorme importancia que adquirió el ecosistema de oasis de niebla costero en el género de vida, tipos de asentamiento y desplazamientos de (...) los cazadores-recolectores marinos del litoral norte. (shrink)

1. L'aspect le plus important du toucher est sa relation au temps et à l'étendue, relation constituée par le mouvement même du toucher. En référence aux conceptions de E. Straus, on expose la distinction entre le toucher et l'être-touché à la lumière d'expériences faites par nous avec des animaux. 2. Le toucher est un être-dans-les-limites-propres et en même temps un franchissement de ces limites, être par lequel l'objet touché est éprouvé à la fois comme „Gegenstand” et comme „Mitseiend”. „Pour le (...) tactile, c'est l'être à deux qui se place au premier rang.” L'affirmation de l'être par le sens du toucher est saisissante dans le cas du se-touchersoi-même, qui est une union exceptionnelle d'activité et de passivité. 3. La reconnaissance tactile de la forme présente elle aussi une dialectique d'activité et de passivité, dialectique qui procède sous la forme d'un développement surmontant le temps, et cela à partir d'un schéma produit dans l'acte même de préhension. On renvoie aux études de V. von Weizsäcker sur le „Gestaltkreis”. Il faut se rappeler aussi l'inquiétude primaire de la main, qui dans le jeu de la main avec un objet devient perdurante. 4. La main peut enserrer un objet. En ce faisant une image schématique tactile est donnée, image qui fonctionne comme hypothèse ou comme principe organisateur du développement prolèptique de l'exploration tactile ultérieure. L'analyse phénoménologique du toucher avec la main se révèle comme une préfiguration de la pensée par jugements synthétiques. Il est donc vrai, comme le remarquait Herder et comme le confirmaient Goldstein et Merleau-Ponty, que la perception telle que l'homme l'effectue et l'existence spirituelle sont identiques. 5. En se référant aux recherches de Révèsz et de Palagyi, on analyse le caractère propre du monde tactil. L'exploration tactile procède selon un véritable développement, donnant lieu à des déterminations anticipatives et rétrospectives qui assurent la continuité de l'événement et de son sens. La perception tactile permet de décrire l'unité continue des phases discontinues objectivement constatables, „comme si” attente et souvenir, jugements provisoires et vérification, fixations conceptuelles et corrections étaient mises en œuvre. 6. Important est l'aspect affectif et émotif des impressions tactiles et leur rapport aux relations interhumaines. 7. Par le toucher l'homme se trouve d'une manière „sensible” en relation personnelle avec cette matérialité des choses qui demeure cachée aux sens-à-distance. Cette participation a un double aspect. Elle est comme le surgissement d'un „état d'âme”, une '‚Befindlichkeit”, mais en même temps elle est le point de départ actif d'un sentir, d'un „comprendre”, d'un „saisir par le dedans”, d'un être-ému, d'un être-frappé par l'objet touché qui se rend présent comme un „quale” propre, comme une matière, comme un être-en-soi. On rappelle le caractère propre du caresser, par lequel l'„être à deux” de l'objet caressé devient complémentaire avec celui du caressant actif. Les concepts usuels par le moyen desquels, dans la vie pratiquement et gnostiquement vécue, sont indiquées les qualités tactiles les plus importantes, ont comme but de nous référer aux propriétés des choses qui prennent place dans le monde géométrique et dans l'espace objectivement mesurable et qui fondent notre orientation naturelle. On rappelle les recherches de von Homborstel au sujet des propriétés internodales des impressions tactiles. Celles-ci nous montrent comment un „savoir” qui accompagne ta perception peut changer une impression sensible. La relation affective, déterminée par un „savoir” nuancé et par un système de valeurs, change la réalité tangible, la substantialité du corps, de la „chair”. Ce changement affectif de la matière, cette „transsubstantiation phénoménale” peut se réaliser facilement par rapport à des objets dont nous savons qu'ils appartiennent ou ont appartenu à quelqu'un. La signification qu'a une chose change la matière de l'objet, objet qui, précisément par le toucher, se rend présent „en chair et en os”. On illustre ceci avec plus de précision grâce aux phénomènes du fétichisme et grâce à de simples expériences de la vie courante. Si nous cherchons un point de vue anthropologique à partir duquel le toucher, dont la main réalise les possibilités, peut prendre un sens, une approche d'un tel point de vue devra s'effectuer à partir de la certitude non-représentable que l'unité ontique de la nature et de l'esprit est dans l'homme la réalité d'une participation possible, participation qui, dans notre existence, n'est qu'indiquée. L'„inquiétude” de la main jamais remplie et toujours chercheuse que nous avons remarquée, est le signe humain de notre existence concrète. Ainsi le toucher nous montre ce que Valéry remarquait à propos de l'esprit : „L'esprit est à la merci du corps, comme les aveugles sont à la merci des voyants.”. (shrink)

Wim Bakker e Arnold van Gemert hanno recentemente licenziato per la stampa l'edizione critica del Θϱηνος εἰς τὰ Πάθη ϰαὶ τὴν Σταύϱωσιν του Кυϱίου ϰαὶ Θεου ϰαὶ Σωτηϱος ἡμων Ἰησου Хϱιστου, poema drammatico unico nel suo genere, in versi decapentasillabi (in gran parte rimati). L'opera è anche l'unica, tra quelle composte dal poeta cretese Marinos Falieros (1395?–1474) e pervenute fino a noi (complessivamente cinque), ad aver avuto l'onore di esser sottoposta ai torchi dei tipografi veneziani nel Cinquecento. Almeno fino ad (...) oggi non è stato reperito in nessuna biblioteca alcun esemplare di questa cinquecentina. Si è salvato solo un apografo, Tubing. Mb 27, f. 171–184, datato 22 gennaio 1585 e copiato per Martinus Crusius dall'allievo Daniel Schuhmaier. Il componimento di Falieros è arrivato quindi fino a noi solo per un caso fortunato, tramite una sola fonte indiretta, una copia manoscritta di un'unica edizione a stampa (1543/44). (shrink)

Correspondence theories are frequently either too vaguely expressed – “true statements correspond to the way things are in the world,” or implausible – “true statements mirror raw, mind-independent reality.” I address this problem by developing features and roles that ought to characterize what I call ldquo;modest” correspondence theories. Of special importance is the role of correspondence in directing our responses to cases of suspected non-factuality; lack of straightforward correspondence shows the need for, and guides us in our choice of, various (...) kinds of reconstrual projects. This, I argue, is in contrast to the approaches suggested by deflationism and coherence, and thus modest correspondence theories are appropriately distinct from rivals. (shrink)

Social problems such as racism, sexism, and inequality are often cited as structural rather than individual in nature. What does it mean to invoke a social structural explanation, and how do such explanations relate to individualistic ones? This article explores recent philosophical debates concerning the nature and usages of social structural explanation. I distinguish between two central kinds of social structural explanation: those that are autonomous from psychology, and those that are not. This distinction will help clarify the explanatory power (...) that each type of SSE has, points of convergence with methodological traditions such as critical theory and rational choice theory, and the difficulties that each type of SSE faces. (shrink)