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)

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)

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)

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)

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)

Introduction, by J. L. Hevesi.--Days of reading, by M. Proust.--Poetry and abstract thought, by P. Valèry.--Jacob Cow the pirate; or, Whether words are signs, by J. Paulhan.--Concerning the pebble, by F. Ponge.--The journey and the return, by J. P. Sartre.--The power of words, by B. Parain.

Why is there a 'hard problem' of consciousness? Why do we seem unable to grasp intuitively that physical brain processes can be identical to experiences? Here I comment on the 'meta-problem' (Chalmers, 2018), based on previous ideas (Storm, 2014; 2018). In short: humans may be 'inborn dualists' ('neuroscepticism'), because evolution gave us two (types of) brain systems (or functional modes): one (Sp) for understanding relatively simple physical phenomena, and another (Sm) specialized for mental phenomena. Because Sp cannot deal with the (...) immense complexity of the brain processes underlying consciousness, it represents them as fundamentally different from nonmental physical phenomena (dualist intuition), using 'simulations' to produce 'Sm-type understanding'/predictions that seems radically different from 'Sp-type understanding'. (By analogy, different sensory modalities, handled by distinct brain systems, evoke qualitatively different experiences.) Brain systems for Sp representations of our brain processes never evolved, because they would be useless. When lacking a single 'template' matching different aspects of reality (objective vs. subjective = simulated), complementary 'models' are needed ('neuro-complementarity'), like the wave–particle duality in quantum mechanics. Thus, it seems plausible that Sp and Sm evolved because they were needed to cope with different challenges, and that 'problem intuitions' are side effects of these useful but different brain systems. (shrink)

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).

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.

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.