The direction and specificity of endolysosomal membrane trafficking is tightly regulated by various cytosolic and membrane‐bound factors, including soluble NSF attachment protein receptors (SNAREs), Rab GTPases, and phosphoinositides. Another trafficking regulatory factor is juxta‐organellar Ca2+, which is hypothesized to be released from the lumen of endolysosomes and to be present at higher concentrations near fusion/fission sites. The recent identification and characterization of several Ca2+ channel proteins from endolysosomal membranes has provided a unique opportunity to examine the roles of Ca2+ and (...) Ca2+ channels in the membrane trafficking of endolysosomes. SNAREs, Rab GTPases, and phosphoinositides have been reported to regulate plasma membrane ion channels, thereby suggesting that these trafficking regulators may also modulate endolysosomal dynamics by controlling Ca2+ flux across endolysosomal membranes. In this paper, we discuss the roles of phosphoinositides, Ca2+, and potential interactions between endolysosomal Ca2+ channels and phosphoinositides in endolysosomal dynamics. (shrink)

Primary and methyl aliphatic halides and tosylates undergo substitution reactions with nucleophiles in one step by the classic S N 2 mechanism, which is characterized by second-order kinetics and inversion of configuration at the reaction center. Tertiary aliphatic halides and tosylates undergo substitution reactions with nucleophiles in two (or more) steps by the classic S N 1 mechanism, which is characterized by first-order kinetics and incomplete inversion of configuration at the reaction center due to the presence of ion pairs. When (...) the nucleophile is also the solvent, the substitution reaction is called a solvolysis, and both the S N 2 and S N 1 reactions now obey first-order kinetics. Schleyer and Bentley have provided solid, but not conclusive, evidence that secondary substrates undergo solvolysis by a merged mechanism, one that blends characteristics of both the S N 2 and S N 1 mechanisms. The following paper presents the history of their sustained pursuit of a merged mechanism and subsequent rebuttals to this claim. Several issues related to the philosophy and sociology of science are also discussed. (shrink)

A new theory concerning charge separation of atmospheric electricity is proposed, based on the selective capture of negative charge from atmospheric ion pairs by material surfaces. It explains why the earth's surface becomes negatively charged during fine weather, and provides a mechanism for the phenomenon of charge separation within clouds during the violent growth of thunderstorms. Also included is a description of laboratory and field experiments substantiating our views.

This short article pairs the realms of “Mathematics”, “Philosophy”, and “Poetry”, presenting some corners of intersection of this type of scientocreativity. Poetry have long been following mathematical patterns expressed by stern formal restrictions, as the strong metrical structure of ancient Greek heroic epic, or the consistent meter with standardized rhyme scheme and a “volta” of Italian sonnets. Poetry was always connected to Philosophy, and further on, notable mathematicians, like the inventor of quaternions, William Rowan Hamilton, or Ion Barbu, the creator (...) of the Barbilian spaces, have written appreciated poems. We will focus here on an avant-garde movement in literature, art, philosophy, and science, called Paradoxism, founded in Romania in 1980 by a mathematician, philosopher and poet, and on the laboured writing exercises of the Oulipo group, founded in Paris in 1960 by mathematicians and poets, both of them still in act. (shrink)

The question we have been investigating is whether the nonlocality of standard quantum mechanics is the private domain of Nature, as is generally assumed by the physics community, or whether in special circumstances the nonlocal connection between subsystems can be used to send signals from one observer to another. With the aid of generous private contributions and some use of CENPA resources, we have continued the work on this test of nonlocal quantum communication, which has been reported in the past (...) three years1�2�3. The initial configuration of the experiment, as described in the first two references, employed a high power argon-ion laser operating at about 1 W in the ultraviolet at 351 nm that pumped nonlinear crystals (BBO or LiIO3) to produce pairs of momentum-entangled 702 nm photons, on which measurements were subsequently performed. It was concluded that signal-to-noise limitations from fluoresence photons competing with the down-converted photons prevented the planned measurements using the initial configuration. (shrink)

Freely falling point-like objects converge toward the center of the Earth. Hence the gravitational field of the Earth is inhomogeneous, and possesses a tidal component. The free fall of an extended quantum mechanical object such as a hydrogen atom prepared in a high principal-quantum-number state, i.e. a circular Rydberg atom, is predicted to fall more slowly than a classical point-like object, when both objects are dropped from the same height above the Earth’s surface. This indicates that, apart from transitions between (...) quantum states, the atom exhibits a kind of quantum mechanical incompressibility during free fall in inhomogeneous, tidal gravitational fields like those of the Earth.A superconducting ring-like system with a persistent current circulating around it behaves like the circular Rydberg atom during free fall. Like the electronic wavefunction of the freely falling atom, the Cooper-pair wavefunction is quantum mechanically incompressible. The ions in the lattice of the superconductor, however, are not incompressible, since they do not possess a globally coherent quantum phase. The resulting difference during free fall in the response of the nonlocalizable Cooper pairs of electrons and the localizable ions to inhomogeneous gravitational fields is predicted to lead to a charge separation effect, which in turn leads to a large Coulomb force that opposes the convergence caused by the tidal gravitational force on the superconducting system.A “Cavendish-like” experiment is proposed for observing the charge separation effect induced by inhomogeneous gravitational fields in a superconducting circuit. The charge separation effect is determined to be limited by a pair-breaking process that occurs when low frequency gravitational perturbations are present. (shrink)

Structures of multisubunit RNA polymerases strongly differ from the many known structures of single subunit DNA and RNA polymerases. However, in functional complexes of these diverse enzymes, nucleic acids take a similar course through the active center. This finding allows superposition of diverse polymerases and reveals features that are functionally equivalent. The entering DNA duplex is bent by almost 90° with respect to the exiting template–product duplex. At the point of bending, a dramatic twist between subsequent DNA template bases aligns (...) the “coding“ base with the binding site for the incoming nucleoside triphosphate (NTP). The NTP enters through an opening that is found in all polymerases, and, in most cases, binds between an α‐helix and two catalytic metal ions. Subsequent phosphodiester bond formation adds a new base pair to the exiting template–product duplex, which is always bound from the minor groove side. All polymerases may undergo “induced fit” upon nucleic acid binding, but the underlying conformational changes differ. BioEssays 24:724–729, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The two center time dependent Dirac equation, for an electron in the external field of two colliding ultrarelativistic heavy ions is considered. In the ultrarelativistic limit, the ions are practically moving at the speed of light and the electromagnetic fields of the ions are confined to the light fronts by the extreme Lorentz contraction and by the choice of gauge, designed to remove the long-range Coulomb effects. An exact solution to the ultrarelativistic limit of the two-center Dirac equation is found (...) by using light-front variables and a light-fronts representation. Previously unexplained experimental results obtained at CERN's SPS are explained in this way and predictions are made as to where one should look, in momentum space, and in space-time, if one wants to study and observe non-perturbative electromagnetic pair-production effects in extremely relativistic heavy-ion collisions. (shrink)

The facts concerning the occurrence of superconductivity in R 2- z Ce z CuO 4 and in R 2- z Th z CuO 4 are studied using a combination of simple tools: a hard-sphere model, the self-consistent bond-valence-sum method and Madelung potential calculations. Doping by isolated substitutional Ce should produce Ce 3+ , and not Ce 4+ , causing us to conclude that the dopants are not isolated, but pairs, which make the material p type and not n type. The (...) L = 0 magnetic rare-earth ions Gd and Cm are unsplit pair breakers, unlike the other magnetic rare-earth ions which lead to superconductivity. As the rare-earth ions become smaller, the c -axis length shortens; then the O ions rotate after they come into contact with one another. Eu 1.85 Th 0.15 CuO 4 does not superconduct because quadrivalent Th is too large to fit at the dopant site, but Eu 1.85 Ce 0.15 CuO 4 does superconduct because Ce fits. (shrink)

Phosphoinositide (PI) phosphatases such as the SH2 domain‐containing inositol 5‐phosphatases 1/2 (SHIP1 and 2) are important signalling enzymes in human physiopathology. SHIP1/2 interact with a large number of immune and growth factor receptors. Tyrosine phosphorylation of SHIP1/2 has been considered to be the determining regulatory modification. However, here we present a hypothesis, based on recent key publications, highlighting the determining role of Ser/Thr phosphorylation in regulating several key properties of SHIP1/2. Since a subunit of the Ser/Thr phosphatase PP2A has been (...) shown to interact with SHIP2, a putative mechanism for reversing SHIP2 Ser/Thr phosphorylation can be anticipated. PI phosphatases are potential target molecules in human diseases, particularly, but not exclusively, in cancer and diabetes. Therefore, this novel regulatory mechanism deserves further attention in the hunt for discovering novel or complementary therapeutic strategies. This mechanism may be more broadly involved in regulating PI signalling in the case of synaptojanin1 or the phosphatase, tensin homolog, deleted on chromosome TEN.Editor's suggested further reading in BioEssays: Pairing phosphoinositides with calcium ions in endolysosomal dynamics Abstract. (shrink)

Nature Exposed to our Method of Questioning explores how we create our cultural assumptions about personhood, culture and nature.

In this commentary, I will argue that the componential and emergent views of cognitive control as defined by Cooper (2010) do not necessarily oppose each other, and I will try to make a case for their interdependence. First, I will use the construct of cognitive inhibition—one of the main componential control functions mentioned in the target articles—to illustrate my line of reasoning. Then, I will comment on how some of the target articles, each from a different perspective, bring arguments in (...) favor of this integrative view. (shrink)

The article analyses the psychological aspects of “phantasy presentation” in Brentano’s lecture Ausgewählte Fragen aus Psychologie und Ästhetik dated 1885/1886. It focuses primarily on two major aspects of Brentano’s work: (1) the traditional understanding of phantasy presentation as intuitive presentation, and as fundamentally related to the perceptual presentation; (2) Brentano’s conception according to which phantasy presentations are “concepts with intuitive nucleus”. In this context, the text focuses on the following topics: the relation between the inauthentic presentations of the phantasy and (...) perceptual presentations; the relation between presentations with attributive unity and surrogate presentations in logic; and the relation between the intuitive and conceptual element in the constitution of phantasy presentations. The study argues that, despite the title of the lecture—Ausgewählte Fragen aus Psychologie und Ästhetik—Brentano’s analysis of phantasy presentation does not refer to the aesthetic function, but to the psychological function of this presentation. Furthermore, it argues that the psychological aspect of phantasy presentation represents one of the main aspects of Brentano’s work, subsequently used by Husserl in his studies to underline the differences between the perceptual and phantasy presentation. (shrink)

Descartes is considered to be the founder of modern rationalism. This is a clear statement which, however, does not show the manner in which rationalism as such appeared in the history of science, taking into account the turmoil of the Renaissance centuries, the significance of the Reform and the birth of modern science. As a founder of a new metaphysics, Descartes, through his work, remains par excellence the case in which the scholastic and Renaissance aftermaths as well as the Reform (...) mutations are mixed in a new synthesis that will be called modernity. This study focuses on reinterpreting Cartesianism from this perspective in the vast context of modernity’s metaphysical significance – it is a hypothesis that will need to be developed not only by means of hermeneutical instruments but, especially, by means of those instruments belonging to the history of culture and anthropology. (shrink)

The aim of this paper is to argue in favor of the idea that it is possible not only to give a special place to reason in our life and in society, but also to offer an integrative rational framework, in in which human ends and goals find their rational expression. The text has three parts. The first describes Alfred Schutz's practical-hermeneutical approach to law and normativity, while making room for a subjective practice of reason. The second proposes to reveal, (...) through the description of knowledge in the world of ordinary life, a form of rationality which offers us practical but consistent ways of making a decision. Ultimately, the third aims at the practical-hermeneutical reconstruction of the law, in order to integrate into the core of legal reasoning references to ends and purposes without prejudicing the objectivity of the reasoning itself. The study aims to make a contribution to the problem of dedifferentiation and positivism of practice in the modern world. Le but de ce papier est d’argumenter en la faveur de l’idée qu’il est possible non seulement de donner une place particulière à la raison dans notre vie et dans la société, mais aussi d’offrir un cadre rationnel intégratif, dans lequel les fins et buts humains trouvent leur expression rationnelle. Le texte comporte trois parties. La première décrit l’approche pratique-herméneutique d’Alfred Schutz à l’égard de la loi et de la normativité, tout en faisant place à une pratique subjective de la raison. La deuxième se propose de dévoiler, à travers la description de la connaissance dans le monde de la vie ordinaire, une forme de rationalité qui nous offre des voies pratiques mais consistantes de prendre une décision. En fin de compte, la troisième vise la reconstruction pratique-herméneutique de la loi, afin d’intégrer dans le noyau du raisonnement légal des références à des fins et buts sans porter préjudice à l’objectivité du raisonnement lui-même. L’étude veut apporter une contribution au problème de la dédifférenciation et du positivisme pratique dans le monde moderne. (shrink)

Le plus ancien exemple de l'utilisation de statues féminines pour remplacer des colonnes se trouvant à Delphes, l'article suggère que ce sont les exigences du sanctuaire, avec son espace réduit, qui sont en quelque sorte à l'origine de ce type. Ces figures peuvent être mises en relation avec un petit groupe de trésors éoliques et ioniques de Delphes qui étaient ornés d'une profusion de moulures au décor élaboré. La richesse de l'architecture y était rehaussée par l'addition de la sculpture et (...) par l'introduction d'une frise ionique sculptée continue à la place des denticules. La grande taille des moulures suggère qu'à Delphes les architectes ioniens tentèrent de reproduire en miniature la profusion et l'élégance des grands temples monumentaux de leur patrie. C'est dans le cadre de ce processus de miniaturisation que la figure féminine isolée aurait été introduite, à la place des tambours de colonnes sculptés utilisés dans les temples colossaux d'Ionie de l'Est. L'idée, reprise ensuite par l'architecte de l'Érechthéion, se serait répandue à partir d'Athènes. (shrink)