Class I PI 3‐kinases signal by producing the signaling lipid phosphatidylinositol(3,4,5) trisphosphate, which in turn acts by recruiting downstream effectors that contain specific lipid‐binding domains. The class I PI 3‐kinases comprise four distinct catalytic subunits linked to one of seven different regulatory subunits. All the class I PI 3‐kinases produce the same signaling lipid, PIP3, and the different isoforms have overlapping expression patterns and are coupled to overlapping sets of upstream activators. Nonetheless, studies in cultured cells and in animals have (...) demonstrated that the different isoforms are coupled to distinct ranges of downstream responses. This review focuses on the mechanisms by which the production of a common product, PIP3, can produce isoform‐specific signaling by PI 3‐kinases.Editor's suggested further reading in BioEssays: Phosphatidylinositol 4,5‐bisphosphate: Targeted production and signaling AbstractHow does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity? Abstract. (shrink)

Phosphatidylinositol 3 kinase (PI 3-kinase) is an important enzyme that is involved in the regulation of a variety of biological processes such as apoptosis, cell division, and ion channel activity and can play a role in the pathological development of a number of diseases, including AIDS and cancer. The authors’ data indicate that external qi of Yan Xin Life Science Technology (YXLST) can modulate enzyme activity in two directions. Within a time window of 3 days of the initial (...) emission of external qi of YXLST, PI 3-kinase activity was restored in an outdated enzyme sample that had lost activity, and PI 3-kinase activity was suppressed in a freshly purified sample relative to an untreated control sample so that its activity was nearly undetectable. The data presented are consistent with the hypothesis that external qi of YXLST can alter molecular events. The uniqueness of this and other observations mandates further study. (shrink)

Phosphatidylinositol 3‐phosphate (PtdIns3P) is generated on the cytosolic leaflet of cellular membranes, primarily by phosphorylation of phosphatidylinositol by class II and class III phosphatidylinositol 3‐kinases. The bulk of this lipid is found on the limiting and intraluminal membranes of endosomes, but it can also be detected in domains of phagosomes, autophagosome precursors, cytokinetic bridges, the plasma membrane and the nucleus. PtdIns3P controls cellular functions through recruitment of specific protein effectors, many of which contain FYVE or PX domains. Cellular processes known (...) to be controlled by PtdIns3P and its effectors include endosomal fusion, sorting and motility, autophagy, cytokinesis, regulated exocytosis and signal transduction. Here we discuss how Ptdins3P is generated on specific cellular membranes, how its localizations and functions can be studied, and how its effectors serve to control cellular functions.Editor's suggested further reading in BioEssays:Phosphatidylinositol 4,5‐bisphosphate: Targeted production and signalingAbstractHow does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity?AbstractPhosphatidylinositol‐3,4,5‐trisphosphate: Tool of choice for class I PI 3‐kinasesAbstractPhosphatidylinositol‐4‐phosphate: The Golgi and beyondAbstract. (shrink)

Insulin resistance is thought to be the primary defect in the pathophysiology of type 2 diabetes. Thus, understanding the cellular mechanisms of insulin action may contribute significantly to developing new treatments for this disease. Although the effects of insulin on glucose and lipid metabolism are well documented, gaps remain in our understanding of the precise molecular mechanisms of signal transduction for the hormone. One potential clue to understanding the unique cellular effects of insulin may lie in the compartmentalization of signaling (...) molecules and metabolic enzymes. We review this evidence, and speculate on how PI-3 kinase-independent and -dependent signaling pathways both diverge from the insulin receptor and converge at discrete targets to insure the specificity of insulin action. BioEssays 23:215–222, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Phosphatidylinositol‐3‐kinases (PI3Ks) are lipid kinases that produce 3‐phosphorylated derivatives of phosphatidylinositol upon activation by various cues. These 3‐phosphorylated lipids bind to various protein effectors to control many cellular functions. Lipid phosphatases such as phosphatase and tensin homolog (PTEN) terminate PI3K‐derived signals and are critical to ensure appropriate signaling outcomes. Many lines of evidence indicate that PI3Ks and PTEN, as well as some specific lipid effectors are highly compartmentalized, either in plasma membrane nanodomains or in endosomal compartments. We examine the evidence (...) for specific recruitment of PI3Ks, PTEN, and other related enzymes to membrane nanodomains and endocytic compartments. We then examine the hypothesis that scaffolding of the sources (PI3Ks), terminators (PTEN), and effectors of these lipid signals with a common plasma membrane nanodomain may achieve highly localized lipid signaling and ensure selective activation of specific effectors. This highlights the importance of spatial regulation of PI3K signaling in various physiological and disease contexts. (shrink)

Currently, a central question in biology is how signals from the cell surface modulate intracellular processes. In recent years phosphoinositides have been shown to play a key role in signal transduction. Two phosphoinositide pathways have been characterized, to date. In the canonical phosphoinositide turnover pathway, activation of phosphatidylinositol‐specific phospholipase C results in the hydrolysis of phosphatidylinositol 4,5‐bisphospate and the generation of two second messengers, inositol 1,4,5‐trisphosphate and diacylglycerol. The 3‐phosphoinositide pathway involves protein‐tyrosine kinase‐mediated recruitment and activation of phosphatidylinositol 3‐ (...) class='Hi'>kinase, resulting in the production of phosphatidylinositol 3,4‐bisphosphate and phosphatidylinositol 3,4,5‐trisphosphate. The 3‐phosphoinositides are not substrates of any known phospholipase C, are not components of the canonical phosphoinositide turnover pathway, and may themselves act as intracellular mediators. The 3‐phosphoinositide pathway has been implicated in growth factor‐dependent mitogenesis, membrane ruffling and glucose uptake. Furthermore the homology of the yeast vps34 with the mammalian phosphatidylinositol 3‐kinase has suggested a role for this pathway in vesicular trafficking.In this review the different mechanisms employed by protein‐tyrosine kinases to activate phosphatidylinositol 3‐kinase, and its involvement in the signaling cascade initiated by tyrosine phosphorylation, are examined. (shrink)

Cell signalling mediators derived from membrane phospholipids are frequent participants in biological processes. The family of phosphoinositide 3-kinases (PI3Ks) phosphorylate the membrane lipid phosphatidylinositol, generating second messengers that direct diverse responses. These PI3K products are fundamental for leukocyte migration or chemotaxis, a pivotal event during the immune response. This system is therefore of significant biomedical interest. This review focuses on the biochemistry and signalling pathways of PI3K, with particular emphasis on chemokine (chemotactic cytokine)-directed responses. The key objectives of chemotaxis are (...) motility and direction. The latter—direction—requires distinct events at the front and back of a cell. In light of this, the coordinated localisation of signalling factors, an event choreographed by a sharp intracellular gradient of PI3K-derived products, is a common theme. BioEssays 27:153–163, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

We show that there is a $$ \varvec{\Sigma }_4^0$$ ideal such that it’s neither extendable to any $$ \varvec{\Pi }_3^0$$ ideal nor above the ideal $$ \textrm{Fin}\times \textrm{Fin} $$ in the sense of Katětov order, answering a question from M. Hrušák.

If there is a good $\Delta^1_3$ wellordering of the reals, then there is a $\Pi^1_1$ wellfounded relation for which the comparison relation is not projective.

Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2), reveal an intriguingly diverse list of downstream pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as links to neurodegenerative diseases. Derived from the structural lipid phosphatidylinositol, PI(3,5)P2 is dynamically generated on multiple cellular compartments where interactions with an increasing list of effectors regulate many cellular pathways. A complex of proteins that includes Fab1/PIKfyve, Vac14, and Fig4/Sac3 mediates the biosynthesis of PI(3,5)P2, and mutations that disrupt complex function and/or (...) formation cause profound consequences in cells. Surprisingly, mutations in this pathway are linked with neurological diseases, including Charcot‐Marie‐Tooth syndrome and amyotrophic lateral sclerosis. Future studies of PI(3,5)P2 and PI5P are likely to expand the roles of these lipids in regulation of cellular functions, as well as provide new approaches for treatment of some neurological diseases. (shrink)

An ω-set is a subset of the recursive ordinals whose complement with respect to the recursive ordinals is unbounded and has order type ω. This concept has proved fruitful in the study of sets in relation to metarecursion theory. We prove that the metadegrees of the sets coincide with those of the meta-r.e. ω-sets. We then show that, given any set, a metacomplete set can be found which is weakly metarecursive in it. It then follows that weak relative metarecursiveness is (...) not a transitive relation on the sets, extending a result of G. Driscoll [2, Theorem 3.1]. Coincidentally, we discuss the notions of total and complete regularity. Finally, we solve Post's problem for the transitive closure of weak relative metarecursiveness. We recommend the reader look at pp. 324–328 of the fundamental article [6] of Kreisel and Sacks before proceeding. He will find there a proof of the following very basic fact: a subset of the integers is iff it is metarecursively enumerable (metafinite). (shrink)

v. 1. 1929-1936 -- v. 2. 1936-1946 -- v. 3. 1948-1955 -- v. 4. 1923-1952.

These are some minor notes and observations related to a paper by Cholak, Jockusch, and Slaman [3].

In lieu of an abstract, here is a brief excerpt of the content:Feeding Tiger, Finding GodScience, Religion, and "the Better Story" in Life of PiGregory Stephens (bio)Yann Martel's Life of Pi is an allegorical castaway story about a sixteen-year-old Indian polytheist who survives 227 days on a lifeboat with a Bengal tiger. Martel frames this postmodern variant on the Noah's ark tale as "a story that will make you believe in God" (viii). But these words are neither Martel's, nor those (...) of the semifictional "Martel-like" narrator one encounters in the "Author's Note" (Innes 25). Rather, they are voiced by Mr. Adirubasamy, an elderly Indian man whom the Canadian quasi-author meets at a coffee house in Pondicherry. The virtual author, like the real Martel, is the author of two failed books, and looking for a capital-S "Story."1 Yet after tracking down the primary narrator of the novel (Pi Patel) in Toronto, reading his diaries of his Pacific Ocean ordeal, and listening to taped interviews with Pi, the quasi-author agreed with Mr. Adirubasamy that "this was, indeed, a story to make you believe in God" (x).That apparently "evangelical premise" could awaken resistance among readers who take this "explicit but deceptive statement" too literally (Ishmael). As one reviewer notes, "Martel's statement is likely to have the opposite effect on his reader, provoking a determined counter-reaction not to succumb to a didactic religious agenda."2 Although the novel has its didactic moments, most reviewers seem to have taken a measured view of the author's "religious agenda." In interviews, Martel notes that he comes from a secular background in Quebec. There are no indications that writing this book represented a Damascus conversion experience for him. Life of Pi is not a conversion narrative perse, but it is in part an ascent narrative (a journey toward enlightenment) that also contains elements of descent narratives.3 As a secular writer with sympathies for the religious imagination, Martel can pitch his revisioning of comparative religion to readers who have what Salman Rushdie once called a "God-shaped hole" in their heart.4 These "implied readers" (Iser) would have a hunger for some of the animating power of faith, if not a capacity for blind commitment to dogmatic faith itself.Reviewing Life of Pi for the Nation, Charlotte Innes describes it as "a religious book that makes sense to a nonreligious person" (25). In similar fashion, the Pequod argues that Martel's book "achieves something more quietly spectacular" than a literal conversion, or a restoring of one's faith in God: "it makes the reader want to believe in God. Martel gives the reader the democratic choice: the desire to believe rather than the belief itself" (Ishmael).Those responses of the secular left contrast sharply with the responses of my first-year students at the University of the West Indies, to whom I have twice taught Life of Pi. For students from a fundamentalist background, it is a challenge to buy into a narrative [End Page 41] that proclaims a God that transcends the imaginations of most believers in the three faiths in which the young Pi has been trained (Hinduism, Christianity, and Islam). In analyzing the theme of finding God, I position the text at a midway point between two different kinds of reception: secular readers for whom the notion of religious belief is at best metaphorical, and religious readers who may resist the narrative's conceit that the true God exists outside the confines of institutional religion.Life of Pi is suffused by a pervasive liminality.5 The teenaged Pi is in motion between continents, between faiths, and between childhood and adulthood, which means that the novel is also a bildungsroman.6 I here focus above all on the text's and Pi's location in the contested space between believers and nonbelievers, and on the novel's attempted mediation between those seeming binary opposites. I ask two perhaps paradoxical questions: In what ways would this be seen by the nonreligious as a religious book with appeal? Put differently, to what degree and in what ways might this text actually give secular readers a desire to believe, even if it does... (shrink)

The German philosopher and philologist Friedrich Ast published this monumental lexicon in three volumes. A professor of classical literature at the University of Landshut and member of the Bavarian Academy of Sciences, Ast wrote widely on the history of philosophy. He edited a complete edition of Plato with Latin translation, identifying spurious interpolations and false attributions, using this as a basis for his Lexicon. The work is arranged alphabetically, Volume 3 covering Pi to Omega. The entries give citations both from (...) Plato and from later works that extensively quote Plato. Though the Lexicon met with criticism for omissions of particles, prepositions and proper names, and the lack of systematic arrangement, it had a high reputation throughout the nineteenth century. It remains a milestone in Plato scholarship and is an indispensable resource for readers interested in the history of philology and methods in textual criticism. (shrink)

[t. 1.] Filosofii︠a︡ -- [t. 2.] Mifologii︠a︡--religii︠a︡-- [t. 3]. Literatura. I︠A︡zyk i pisʹmennostʹ -- [t. 4]. Istoricheskai︠a︡ myslʹ. Politicheskai︠a︡ i pravovai︠a︡ kulʹtura -- [t. 5]. Nauka, tekhnicheskai︠a︡ i voennai︠a︡ myslʹ, zdravookhranenie i obrazovanie -- [t. 6]. Iskusstvo.

The number of cellular events identified as being directly or indirectly modulated by phosphoinositides dramatically increased in the recent years. Part of the complexity results from the fact that the seven phosphoinositides play second messenger functions in many different areas of growth factors and insulin signaling, cytoskeletal organization, membrane dynamics, trafficking, or nuclear signaling. PtdIns(3,4)P2 is commonly reported as a product of the SH2 domain‐containing inositol 5‐phosphatases 1/2 (SHIP1 and SHIP2) that dephosphorylate PtdIns(3,4,5)P3 at the 5‐position. Here we discuss recent (...) interest in PtdIns(3,4)P2 signaling highlighting its involvement in key cellular mechanisms such as cell adhesion, migration, and cytoskeletal regulation. We question and discuss the involvement of SHIP2 either as a PI 5‐phosphatase or as a scaffold protein in insulin signaling, cytoskeletal dynamics, and endocytosis of growth factor receptors. (shrink)

t. 1. Filosofii͡a : samosoznanie cheloveka i obshchestva -- t. 2. Politika i istoriosofii͡a -- t. 3. Politika i diplomatii͡a -- t. 4. Kulʹtura i sovremennostʹ -- t. 5. Zapadnoevropeĭskai͡a filosofii͡a, politika i kulʹtura: problemy i perspektivy.

Joining an antagonistic phosphoinositide (PtdInsP) kinase and phosphatase into a single protein complex may regulate rapid and local PtdInsP changes. This may be important for processes such as membrane fission that require a specific PtdInsP and that are innately local and rapid. Such a complex could couple vesicle formation, with erasing of the identity of the donor organelle from the vesicle prior to its fusion with target organelles, thus preventing organelle identity intermixing. Coordinating signals are postulated to switch the (...) relative activities of the kinase and phosphatase in a spatio‐temporal manner that matches membrane fission events. The discovery of two such complexes supports this hypothesis. One regulates the interconversion of phosphatidylinositol and PtdIns(3)P by joining the Vps34 PtdIns 3‐kinase and the myotubularin 3‐phosphatases. The other regulates the interconversion between PtdIns(3)P and PtdIns(3,5)P2 through the Fab1/PIKfyve kinase and the Fig4/mFig4 phosphatase. These lipids are essential components of the endosomal identity code. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Notes and Discussions THE UNITY OF WISDOM AND TEMPERANCE The attempt of Socrates to establish the unity of the virtues has long been an object of philosophic suspicion. Particular attention has been directed to the argument at Protagoras 332a-333b, in which Socrates seeks to demonstrate the unity of wisdom and temperance, by showing that they must be identified as the contrary of folly. The argument proceeds on the assumption (...) that wisdom and temperance are distinct, and so terminates in a contradiction between 'Whatever admits of a contrary admits of one only' and 'Folly, which is one thing, has two contraries, wisdom and temperance.' Scholars have generally rejected Socrates' proof of the second of the contradictory propositions. However, in a recent paper, Professor David Savan has claimed that the contradiction is derived in a formally valid way from premisses which either need no argument or are accepted by Protagoras} My intent in this paper is to cast doubt on this claim, and so to restore the status quo. According to the critics, the weak point in the argument is Socrates' defence of the statement 'Foolish acts and temperate acts are contraries.' But Saran holds that this statement follows from three conditionals, all stated by Socrates and accepted by Protagoras. These conditionals, referred to by Savan as F G and H, will here be termed P1-3. P1 If an act is right and advantageous, then it is temperate. Symbolically: (r.a) D t P2 If an act is wrong, then it is foolish. w~f P3 If an act is foolish, then it is not temperate. fD -t From these, Saran argues, "it follows that 'An act is right' and 'An act is temperate ' are truth functionallyequivalent, as are 'An act is wrong' and 'An act is foolish'.... Since right and wrong are either contraries or contradictories, temperate and foolish acts must also be either contraries or contradictories" (p. 24). Savan then argues that Protagoras, on the basis of his remarks earlier in the dialogue, must take right and wrong to be contradictories, so that temperate and foolish actions are also contradictories, rather than contraries. I want first to consider whether the material equivalences alleged to follow from P1-3 do in fact follow. They may be symbolized: Clr~t C2w =f It is immediately clear that neither C1 nor C2 follows from P1-3. But this is not surprising, because some expression of the relation between 'right' and 'wrong' 1D. Saran, "Socrates'Logic and the Unity of Wisdom and Temperance," in R. J. Butler (ed.), AnalyticalPhilosophy,2nd series(Oxford: BasilBlackwell,1965),pp. 20-26. [157] 158 HISTORY OF PHILOSOPHY must appear among the premises. Since Savan raises the question whether 'right' and 'wrong' are contraries or contradictories only after he claims to establish C1 and C2, we may suppose that the argument should hold whichever relation we assume. If 'right' and 'wrong' are contraries we add the premise: P4A r D --w And ifthey are contradictorieswe add the stronger premise: P4B r -- --w But neither C1 nor C2 follows from PI-3 together with either P4A or P4B. However, it may be urged, the argument fails only because 'advantageous' has been treated as an independent term. P1 should be replaced by: PI* r ~ t We now find that PI*-3 and P4B are sufficientto derive C1 and C2. But PI*-3 and P4A do not suffice.The most we can establish, using only P4A, is the disjunction : C1 vC2r -- t-v-w -- f And this is useless for the purposes of Socrates' argument. One further way of strengthening the premises might be suggested. Instead of dropping 'advantageous' from the argument, one might take it as related both to 'right' and to 'foolish.' That is, one might introduce additional premises from the pairs: P5A r ~ a P5B r - a and: P6A a D -f P6B a ---- -f P5A, added to P1-3 and P4B, will suffice for the derivation of C1 and C2. But no combination of premises not including P4B will do; from P1-3, P4A, P5B and P6B, one can derive C1 but not C2. It is, therefore, necessary to modify Savan's claim in two fairly important... (shrink)

Phagocytosis is an uptake of large particles governed by the actin-based cytoskeleton. Binding of particles to specific cell surface receptors is the first step of phagocytosis. In higher Eucaryota, the receptors able to mediate phagocytosis are expressed almost exclusively in macrophages, neutrophils, and monocytes, conferring immunodefence properties to these cells. Receptor clustering is thought to occur upon particle binding, that in turn generates a phagocytic signal. Several pathways of phagocytic signal transduction have been identified, including the activation of tyrosine kinases (...) and (or) serine/threonine kinase C in pivotal roles. Kinase activation leads to phosphorylation of the receptors and other proteins, recruited at the sites of phagocytosis. Monomeric GTPases of the Rho and ARF families are likely to be engaged downstream of activated receptors. The GTPases, in cooperation with phosphatidylinositol 4-phosphate 5-kinase and phosphatidylinositol 3-kinase lipid modifying enzymes, can modulate locally the assembly of the submembranous actin filament system leading to particle internalization. BioEssays 21:422–431, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The rate‐limiting step in the uptake and metabolism of Dglucose by insulin target cells is thought to be glucose transport mediated by glucose transporters (primarily the GLUT4 isoform) localized to the plasma membrane. However, subcellular fractionation, photolabelling and immunocytochemical studies have shown that the pool of GLUT4 present in the plasma membrane is only one of many subcellular pools of this protein. GLUT4 has been found in occluded vesicles at the plasma membrane, clathrin‐coated pits and vesicles, early endosomes, and tubulo‐vesicular (...) structures; the latter are analogous to known specialized secretory compartments. Tracking the movement of GLUT4 through these compartments, and defining the mechanism and site of action of insulin in stimulating this subcellular trafficking, are major topics of current investigation. Recent evidence focuses attention on the exocytosis of GLUT4 as the major site of insulin action. Increased exocytosis may be due to decreased retention of glucose transporters in an intracellular pool, or possibly to increased assembly of a vesicle docking and fusion complex. Although details are unknown, the presence in GLUT4 vesicles of a synaptobrevin homologue leads us to propose that a process analogous to that occurring in synaptic vesicle trafficking is involved in the assembly of GLUT4 vesicles into a form suitable for fusion with the plasma membrane. Evidence that the pathways of signalling from the insulin receptor and of GLUT4 vesicle exocytosis may converge at the level of the key signalling enzyme, phosphatidylinositol 3‐kinase, is discussed. (shrink)

We examine how degrees of computably enumerable equivalence relations under computable reduction break down into isomorphism classes. Two ceers are isomorphic if there is a computable permutation of ω which reduces one to the other. As a method of focusing on nontrivial differences in isomorphism classes, we give special attention to weakly precomplete ceers. For any degree, we consider the number of isomorphism types contained in the degree and the number of isomorphism types of weakly precomplete ceers contained in the (...) degree. We show that the number of isomorphism types must be 1 or ω, and it is 1 if and only if the ceer is self-full and has no computable classes. On the other hand, we show that the number of isomorphism types of weakly precomplete ceers contained in the degree can be any member of $[0,\omega ]$. In fact, for any $n \in [0,\omega ]$, there is a degree d and weakly precomplete ceers ${E_1}, \ldots,{E_n}$ in d so that any ceer R in d is isomorphic to ${E_i} \oplus D$ for some $i \le n$ and D a ceer with domain either finite or ω comprised of finitely many computable classes. Thus, up to a trivial equivalence, the degree d splits into exactly n classes.We conclude by answering some lingering open questions from the literature: Gao and Gerdes [11] define the collection of essentially FC ceers to be those which are reducible to a ceer all of whose classes are finite. They show that the index set of essentially FC ceers is ${\rm{\Pi }}_3^0$-hard, though the definition is ${\rm{\Sigma }}_4^0$. We close the gap by showing that the index set is ${\rm{\Sigma }}_4^0$-complete. They also use index sets to show that there is a ceer all of whose classes are computable, but which is not essentially FC, and they ask for an explicit construction, which we provide.Andrews and Sorbi [4] examined strong minimal covers of downwards-closed sets of degrees of ceers. We show that if $\left$ is a uniform c.e. sequence of non universal ceers, then $\left\{ {{ \oplus _{i \le j}}{E_i}|j \in \omega } \right\}$ has infinitely many incomparable strong minimal covers, which we use to answer some open questions from [4].Lastly, we show that there exists an infinite antichain of weakly precomplete ceers. (shrink)

In Chapter IV of his Schreiben und Denken , the Austrian linguist Hanspeter Ortner distinguishes and describes ten writing strategies (“Schreibstrategien”). One of them is “syncretistic writing”. 1 A simple application of Ortner’s defi nition and description of syncretistic writing to the genesis of the Philosophical Investigations (PI) makes clear that the PI can be said to be of syncretistic origin. 2 Wittgenstein’s writing of the PI 3 can be characterized by Ortner’s eight features of syncretistic: his writing (1) hops (...) all over the place (“Sprunghaftigkeit”); (2) combines disparate elements from his writings (“Verbindung von weit Auseinanderliegendem”); (3) is semantically open, under-determined and under-determining (“Unterdeterminiertheit und semantische Offenheit”); (4) postpones gestalt-formation/ elaboration (“Aufschub der Gestaltbildung”); (5) invites and offers many opportunities for creative ideas (“viele Chancen für und Einladungen an den kreativen Einfall”); (6) gives freedom to choose the points of departure and reference (“Freiheit bei der Wahl des/der Startpunktes/e und des/der Gesichtspunktes/e”); (7) is hierarchically under-determined (“hierarchische Unterbestimmtheit”); (8) works side-by-side with the already “fi nished” and the newly begun, which implies long text building processes and parallel operations (“lange ‘Bauzeit’ und Nebeneinander von Fertiggestelltem und Neubegonnenem”). 4 -/- In the following, I will try to show in more detail how the genesis of the PI is characterized by these eight features. First, the writings that constitute the PI’s genesis are characterized by a strong discrepancy between the sequence of remarks in their textual order and the sequence of remarks in their physical order. Texts are put together from chronologically and argumentatively dispersed units. One example is Wittgenstein’s rearrangement of remarks from an earlier dictation (TS 208) into a new text in 1930 (TS 209, published by Rush Rhees as Philosophical Remarks ). In this new text, he abandoned both the original argumentative order and the chronological order and did not necessarily obey the criteria of consistency and coherence, not even on linguistic levels such as demonstrative reference. The work that -/- emerges is seen by many as an unordered agglomerate of remarks, although I have argued that this view can be challenged. 5 The second example is the revision and rearrangement of the so-called Big Typescript (TS 213) in 1933-34, which is paradigmatic in its triple use of (1) the text in the typescript, (2) the handwritten revisions of it in the typescript, and (3) text in other manuscripts. In his edition of the Philosophical Grammar (1969), Rush Rhees has tried to take this complicated network of revisions into account and to follow it painstakingly and faithfully; by looking at the manuscript sources for this edition 6 one realizes how much “hopping all over the place” was going on in the originals. Thirdly, MS 142, the “Urfassung” of the PI, was produced in 1936-37 from remarks stemming from different places in manuscripts and typescripts and various loci of discourse. MS 157b, 13v, contains a list of references to pages in TS 213 from which parts of the text were to be taken to write the “philosophy chapter” of this fi rst PI version; other sources include MS 140 (last page), MS 152, MS 156a, MS 156b and MS 157a, all yielding materials, lists and drafts for the text of MS 142. The fi nal example is TS 228: in the later stages of the PI genesis, Wittgenstein selected about 400 remarks from this typescript to include in TS 227, the typescript used as the printer’s copy for the PI. (shrink)

We consider some natural sets of real numbers arising in ergodic theory and show that they are, respectively, complete in the classes${\cal D}_2 \left( {{\bf{\Pi }}_3^0 } \right)$and${\cal D}_\omega \left( {{\bf{\Pi }}_3^0 } \right)$, that is, the class of sets which are 2-differences (respectively,ω-differences) of${\bf{\Pi }}_3^0 $sets.

We locate winning strategies for various ${\mathrm{\Sigma }}_{3}^{0}$ -games in the L-hierarchy in order to prove the following: Theorem 1. KP+Σ₂-Comprehension $\vdash \exists \alpha L_{\alpha}\ models"\Sigma _{2}-{\bf KP}+\Sigma _{3}^{0}-\text{Determinacy}."$ Alternatively: ${\mathrm{\Pi }}_{3}^{1}\text{\hspace{0.17em}}-{\mathrm{C}\mathrm{A}}_{0}\phantom{\rule{0ex}{0ex}}$ "there is a β-model of ${\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}\text{\hspace{0.17em}}\text{\hspace{0.17em}}+\text{\hspace{0.17 em}}{\mathrm{\Sigma }}_{3}^{0}$ -Determinacy." The implication is not reversible. (The antecedent here may be replaced with ${\mathrm{\Pi }}_{3}^{1}\text{\hspace{0.17em}}\text{\hspace{0.17em}}\left({\mathrm{\Pi }}_{3}^{1}\right)-{\mathrm{C}\mathrm{A}}_{0}:\text{\hspace{0.17em}}{\mathrm{\Pi }}_{3}^{1}$ instances of Comprehension with only ${\mathrm{\Pi }}_{3}^{1}$ -lightface definable parameters—or even weaker theories.) Theorem 2. KP +Δ₂-Comprehension +Σ₂-Replacement + ${\mathrm{\Sigma }}_{3}^{0}\phantom{\rule{0ex}{0ex}}$ -Determinacy. (Here AQI (...) is the assertion that every arithmetical quasi-inductive definition converges.) Alternatively: $\Delta _{3}^{1}{\rm CA}_{0}+{\rm AQI}\nvdash \Sigma _{3}^{0}$ -Determinacy. Hence the theories: ${\mathrm{\Pi }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0},\text{\hspace{0.17em}}{\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}+\text{\hspace{0.17em}}{\mathrm{\Sigma }}_{3}^{0}-\mathrm{D}\mathrm{e}\mathrm{t}\phantom{\rule{0ex}{0ex}}$ -Det, ${\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}+\mathrm{A}\mathrm{Q}\mathrm{I}$ , and ${\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}\phantom{\rule{0ex}{0ex}}$ are in strictly descending order of strength. (shrink)

Abnormalities in the ability of cells to properly degrade proteins have been identified in many neurodegenerative diseases. Recent work has implicated synaptojanin 1 (SynJ1) in Alzheimer's disease and Parkinson's disease, although the role of this polyphosphoinositide phosphatase in protein degradation has not been thoroughly described. Here, we dissected in vivo the role of SynJ1 in endolysosomal trafficking in zebrafish cone photoreceptors using a SynJ1‐deficient zebrafish mutant, nrca14. We found that loss of SynJ1 leads to specific accumulation of late endosomes and (...) autophagosomes early in photoreceptor development. An analysis of autophagic flux revealed that autophagosomes accumulate because of a defect in maturation. In addition we found an increase in vesicles that are highly enriched for PI(3)P, but negative for an early endosome marker in nrca14 cones. A mutational analysis of SynJ1 enzymatic domains found that activity of the 5'phosphatase, but not the Sac1 domain, is required to rescue both aberrant late endosomes and autophagosomes. Finally, modulating activity of the PI(4,5)P2 regulator, Arf6, rescued the disrupted trafficking pathways in nrca14 cones. Our study describes a specific role for SynJ1 in autophagosomal and endosomal trafficking and provides evidence that PI(4,5)P2 participates in autophagy in a neuronal cell type. -/- . (shrink)

In the past decade, the availability of genetically modified animals has enabled the discovery of interesting roles for phosphatidylinositol 3‐kinase‐γ (PI3Kγ) and ‐δ (PI3Kδ) in different cell types orchestrating innate and adaptive immune responses. Therefore, these PI3K isoforms appear to be attractive drug targets for the treatment of diseases caused by unrestrained immune reactions. Currently, pharmacological targeting of PI3Kγ and/or PI3Kδ represents one of the most promising challenges for companies interested in the development of novel safe treatments for inflammatory (...) diseases. In this review we provide a general outline of PI3Kγ‐ and PI3Kδ‐specific functions in distinct subsets of inflammatory cells. We also discuss the therapeutic impact of novel compounds targeting PI3Kγ, PI3Kδ or both, in mouse models of autoimmune disorders (systemic lupus erythematosus (SLE) and rheumatoid arthritis), respiratory diseases (allergic asthma and chronic obstructive pulmonary disease) and cardiovascular dysfunctions (atherosclerosis and myocardial infarction). (shrink)

One of the earliest structural changes observed in cells in response to many extracellular factors is membrane ruffling: the formation of motile cell surface protrusions containing a meshwork of newly polymerized actin filaments. It is becoming clear that actin reorganization is an integral part of early signal transduction pathways, and that many signalling molecules interact with the actin cytoskeleton. The small GTP‐binding protein Rac is a key regulator of membrane ruffling, and proteins that can regulate Rac activity, such as Bcr, (...) are likely to act on this signalling pathway. In addition, several previously characterized signal transducing molecules are implicated in the membrane‐ruffling response, including Ras, the adaptor protein Grb2, phosphatidyl inositol 3‐kinase, phospholipase A2 and phorbol ester‐responsive proteins. Changes in polyphosphoinositide metabolism and intracellular Ca2+ levels may also play a role. A number of actin‐binding and organizing proteins localize to membrane ruffles and are potential targets for these signal transducing molecules. (shrink)

In his Metrica, Hero provides four procedures for finding the area of a circular segment (with b the base of the segment and h its height): an Ancient method for when the segment is smaller than a semicircle, $$(b + h)/2 \, \cdot \, h$$ ( b + h ) / 2 · h ; a Revision, $$(b + h)/2 \, \cdot \, h + (b/2)^{2} /14$$ ( b + h ) / 2 · h + ( b / 2 (...) ) 2 / 14 ; a quasi-Archimedean method (said to be inspired by the quadrature of the parabola) for cases where b is more than triple h, $${\raise0.5ex\hbox{$\scriptstyle 4$} \kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 3$}}(h \, \cdot \, b/2)$$ 4 / 3 ( h · b / 2 ) ; and a method of Subtraction using the Revised method, for when it is larger than a semicircle. He gives superficial arguments that the Ancient method presumes $$\pi = 3$$ π = 3 and the Revision, $$\pi = {\raise0.5ex\hbox{$\scriptstyle {22}$} \kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 7$}}$$ π = 22 / 7. We are left with many questions. How ancient is the Ancient? Why did anyone think it worked? Why would anyone revise it in just this way? In addition, why did Hero think the Revised method did not work when $$b > 3\;h$$ b > 3 h? I show that a fifth century BCE Uruk tablet employs the Ancient method, but possibly with very strange consequences, and that a Ptolemaic Egyptian papyrus that checks this method by comparing the area of a circle calculated from the sum of a regular inscribed polygon and the areas of the segments on its sides as determined by the Ancient method with the area of the circle as calculated from its diameter correctly sees that the calculations do not quite gel in the case of a triangle but do in the case of a square. Both traditions probably could also calculate the area of a segment on an inscribed regular polygon by subtracting the area of the polygon from the area of the circle and dividing by the number of sides of the polygon. I then derive two theorems about pairs of segments, that the reviser of the Ancient method should have known, that explain each method, why they work when they do and do not when they do not, and which lead to a curious generalization of the Revised method. Hero’s comment is right, but not for the reasons he gives. I conclude with an exploration of Hero’s restrictions of the Revised method and Hero’s two alternative methods. (shrink)

We study the first-order consequences of Ramsey’s Theorem fork-colourings ofn-tuples, for fixed$n, k \ge 2$, over the relatively weak second-order arithmetic theory$\mathrm {RCA}^*_0$. Using the Chong–Mourad coding lemma, we show that in a model of$\mathrm {RCA}^*_0$that does not satisfy$\Sigma ^0_1$induction,$\mathrm {RT}^n_k$is equivalent to its relativization to any proper$\Sigma ^0_1$-definable cut, so its truth value remains unchanged in all extensions of the model with the same first-order universe.We give a complete axiomatization of the first-order consequences of$\mathrm {RCA}^*_0 + \mathrm {RT}^n_k$for$n \ge (...) 3$. We show that they form a non-finitely axiomatizable subtheory of$\mathrm {PA}$whose$\Pi _3$fragment coincides with$\mathrm {B} \Sigma _1 + \exp $and whose$\Pi _{\ell +3}$fragment for$\ell \ge 1$lies between$\mathrm {I} \Sigma _\ell \Rightarrow \mathrm {B} \Sigma _{\ell +1}$and$\mathrm {B} \Sigma _{\ell +1}$. We also give a complete axiomatization of the first-order consequences of$\mathrm {RCA}^*_0 + \mathrm {RT}^2_k + \neg \mathrm {I} \Sigma _1$. In general, we show that the first-order consequences of$\mathrm {RCA}^*_0 + \mathrm {RT}^2_k$form a subtheory of$\mathrm {I} \Sigma _2$whose$\Pi _3$fragment coincides with$\mathrm {B} \Sigma _1 + \exp $and whose$\Pi _4$fragment is strictly weaker than$\mathrm {B} \Sigma _2$but not contained in$\mathrm {I} \Sigma _1$.Additionally, we consider a principle$\Delta ^0_2$-$\mathrm {RT}^2_2$which is defined like$\mathrm {RT}^2_2$but with both the$2$-colourings and the solutions allowed to be$\Delta ^0_2$-sets rather than just sets. We show that the behaviour of$\Delta ^0_2$-$\mathrm {RT}^2_2$over$\mathrm {RCA}_0 + \mathrm {B}\Sigma ^0_2$is in many ways analogous to that of$\mathrm {RT}^2_2$over$\mathrm {RCA}^*_0$, and that$\mathrm {RCA}_0 + \mathrm {B} \Sigma ^0_2 + \Delta ^0_2$-$\mathrm {RT}^2_2$is$\Pi _4$- but not$\Pi _5$-conservative over$\mathrm {B} \Sigma _2$. However, the statement we use to witness failure of$\Pi _5$-conservativity is not provable in$\mathrm {RCA}_0 +\mathrm {RT}^2_2$. (shrink)

We prove several trichotomy results for ideals of compact sets. Typically, we show that a "sufficiently rich" universally Baire ideal is either $\Pi _{3}^{0}$-hard, or $\Sigma _{3}^{0}$-hard, or else a σ-ideal.

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)

Phosphatidylinositol 4,5‐bisphosphate (PI4,5P2) is a key lipid signaling molecule that regulates a vast array of biological activities. PI4,5P2 can act directly as a messenger or can be utilized as a precursor to generate other messengers: inositol trisphosphate, diacylglycerol, or phosphatidylinositol 3,4,5‐trisphosphate. PI4,5P2 interacts with hundreds of different effector proteins. The enormous diversity of PI4,5P2 effector proteins and the spatio‐temporal control of PI4,5P2 generation allow PI4,5P2 signaling to control a broad spectrum of cellular functions. PI4,5P2 is synthesized by phosphatidylinositol phosphate kinases (...) (PIPKs). The array of PIPKs in cells enables their targeting to specific subcellular compartments through interactions with targeting factors that are often PI4,5P2 effectors. These interactions are a mechanism to define spatial and temporal PI4,5P2 synthesis and the specificity of PI4,5P2 signaling. In turn, the regulation of PI4,5P2 effectors at specific cellular compartments has implications for understanding how PI4,5P2 controls cellular processes and its role in diseases. (shrink)

Most of the essential cellular components, like nucleic acids, lipids and sugars, are phosphorylated. The phosphate equilibrium in Escherichia coli is regulated by the phosphate (Pi) input from the surrounding medium. Some 90 proteins are synthesized at an increased rate during Pi starvation and the global control of the cellular metabolism requires cross‐talk with other regulatory mechanisms. Since the Pi concentration is normally low in E. coli's natural habitat, these cells have devised a mechanism for synthesis of about 15 proteins (...) to accomplish two specific functions: transport of Pi and its intracellular regulation. The synthesis of these proteins is controlled by two genes (the phoB‐phoR operon), involving both negative and positive functions. PhoR protein is a histidine protein kinase, induced in Pi starvation and is a transmembrane protein. It phosphorylates the regulator protein PhoB which is also Pi starvation‐induced. The PhoB phosphorylated form binds specifically to a DNA sequence of 18 nucleotides (the pho Box), which is part of the promoters of the Pho genes. The genes controlled by phoB constitute the Pho regulon.The repression of phoA (the gene encoding alkaline phosphatase) by high Pi concentrations in the medium requires the presence of an intact Pst operon (pstS, pstC, pstA, pstB and phoU) and phoR. The products of pstA and pstC are membrane bound, whereas the product of pstS is periplasmic and PstB and PhoU proteins are cytoplasmic. The function of the PhoU protein may be regulated by cofactor nucleotides and may be involved in signaling the activation of the regulon via PhoR. (shrink)

Many biologically active compounds including neurotransmitters, metabolic precursors, and certain drugs are accumulated intracellularly by transporters that are coupled to the transmembrane Na+ gradient. Amino acid neurotransmitter transporters play a key role in the regulation of extracellular amino acid concentrations and termination of neurotransmission in the CNSAbbreviations: CNS, central nervous system; GABA, γ‐aminobutyric acid; cDNA, complementary deoxyribonucleic acid; mRNA, messenger ribonucleic acid; NMDA, N‐methyl‐D‐aspartate; PKC, protein kinase C; PMA, phorbol 12‐myristate 13‐acetate; DAG, diacyl glycerol; R59022, DAG kinase inhibitor; (...) AA, arachidonic acid; ACHC, cis‐3‐aminocyclohexanecarboxylic acid; GAT‐A, ACHC‐sensitive GABA transporter; GAT‐B, β‐alanine‐sensitive GABA transporter; GLY‐1 and GLYT‐1, glycine transporters; PROT‐1, proline transporter; BGT‐1, betaine transporter.. Transporters for the major amino acid neurotransmitters glutamate, GABA, and glycine are found in both neurons and glial cells. Recent work has resulted in the identification of cDNAs encoding several amino acid neurotransmitter transport proteins, all of which belong to the Na+‐and Cl−‐dependent transporter gene family. The diversity of this family suggests a degree of transporter heterogeneity that is greater than that indicated by biochemical and pharmacological studies. (shrink)

Let ${2-\textsf{RAN}}$ be the statement that for each real X a real 2-random relative to X exists. We apply program extraction techniques we developed in Kreuzer and Kohlenbach (J. Symb. Log. 77(3):853–895, 2012. doi:10.2178/jsl/1344862165), Kreuzer (Notre Dame J. Formal Log. 53(2):245–265, 2012. doi:10.1215/00294527-1715716) to this principle. Let ${{\textsf{WKL}_0^\omega}}$ be the finite type extension of ${\textsf{WKL}_0}$ . We obtain that one can extract primitive recursive realizers from proofs in ${{\textsf{WKL}_0^\omega} + \Pi^0_1-{\textsf{CP}} + 2-\textsf{RAN}}$ , i.e., if ${{\textsf{WKL}_0^\omega} + \Pi^0_1-{\textsf{CP}} + 2-\textsf{RAN} (...) \, {\vdash} \, \forall{f}\, {\exists}{x} A_{qf}(f,x)}$ then one can extract from the proof a primitive recursive term t(f) such that ${A_{qf}(f,t(f))}$ . As a consequence, we obtain that ${{\textsf{WKL}_0}+ \Pi^0_1 - {\textsf{CP}} + 2-\textsf{RAN}}$ is ${\Pi^0_3}$ -conservative over ${\textsf{RCA}_0}$. (shrink)

In early embryonic development, the cell cycle is paced by a biochemical oscillator involving cyclins and cyclin-dependent kinases (cdks). Essentially the same machinery operates in all eukaryotic cells, although after the first few divisions various braking mechanisms (the so-called checkpoints) become significant. Haase and Reed have recently shown that yeast cells have a second, independent oscillator which coordinates some of the events of the G1 phase of the cell cycle.(1) Although the biochemical nature of this oscillator is not known,it seems (...) unlikely to be a redundant cyclin/cdk system. BioEssays 22:3–5, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

The no-miracles argument is the main inference-to-the-best-explanation kind of argument for scientific realism, and the pessimistic induction is considered a main, if not the main, challenge for a NMA-based scientific realism. Doppelt advocates a new kind of inference-to-the-best-explanation supported scientific realism that he labels Best Theory Realism. If successful in replacing standard selective realism as the best version of scientific realism, BTR would be particularly good since it is not committed to the partial truth of past theories and thereby it (...) is immune to the antirealist strategy of finding cases of past, predictively successful theories with predictively essential components not retained by later theories. The goal of this paper is to raise doubts about Doppelt’s attempt and argue that, other benefits of his proposal notwithstanding, it fails. In section 1 I summarize the main tenets of standard, retentive selective realism relevant for the present discussion. In section 2 I show that Doppelt’s main arguments against retentive selective realism do not work. In section 3, I argue that the way BTR faces the challenge posed by the historical record that motivates PI is unsatisfactory and puts Doppelt into a fatal trilemma: either he is committed to two claims that are untenable together; or endorses an extremely implausible form of present-science chauvinism; or unjustifiably discriminates explanation against prediction in historical record. The conclusion is that BTR falls short of substituting standard retentive selective realism as the most plausible realist position, and that thereby the cases of past successful theories with predictively essential parts not retained by posterior theories are still a real problem for a plausible realist position. (shrink)

In order to test a mathematical model of G1/S-phase transition, the proliferative response of the murine myeloid interleukin 3 (IL-3) dependent cell line NFS-78 to graded reduction of IL-3 levels was measured. Exponentially growing cells were exposed to bromodeoxyuridine (BUdR), which replaces thymidine (TdR) in the DNA double strands during DNA synthesis. After incubation periods ranging from 3 to 36 h the cells were fixed and stained with a fluorescence dye mixture of Hoechst 33258 and ethidium bromide (EB) and subsequently (...) analyzed in a two-parametrical flow cytometer. The BUdR-quenched TdR-specific Hoechst 33258 fluorescence of each cell provides information on the cell cycle location at the start of incubation and on whether or not a cell has divided. The DNA-specific EB fluorescence provides information on the actual cell cycle location at the end of the incubation period. From the 2-dimensional fluorescence distributions the efflux from G1-phase was calculated. Upon IL-3 reduction the cells showed accumulation in the Gl-phase along with a reduction in the progression rate through the other phases of the cell cycle. By staining with the vital dye Hoechst 33342 as well as with propidium iodide (PI) it was further possible to show that cell death after IL-3 withdrawal occurred in all phases of the cell cycle. (shrink)

Recent years have witnessed tremendous growth in the epidermal growth factor (EGF) family of peptide growth factors and the ErbB family of tyrosine kinases, the receptors for these factors. Accompanying this growth has been an increased appreciation for the roles these molecules play in tumorigenesis and in regulating cell proliferation and differentiation during development. Consequently, a significant question has been how diverse biological responses are specified by these hormones and receptors. Here we discuss several characteristics of hormone-receptor interactions and receptor (...) coupling that contribute to specificity: 1) a single EGF family hormone can bind multiple receptors; 2) a single ErbB family receptor can bind multiple hormones; 3) there are three distinct functional groups of EGF family hormones; 4) EGF family hormones can activate receptors in trans, and this heterodimerization diversifies biological responses; 5) ErbB3 requires a receptor partner for signaling; and 6) ErbB family receptors differentially couple to signaling pathways and biological responses. BioEssays 20:41–48, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Negative workplace gossip generates social undermining and great side effects to employees. But, the damage of negative gossip is mainly aimed at the employee who perceived being targeted. The purpose of this study is to develop a conceptual model in which perceived negative workplace gossip influences employees in-role behavior and organizational citizenship behavior differentially by changing employees’ self-concept (organizational-based self-esteem and perceived insider status). 336 employees from seven Chinese companies were investigated for empirical analysis on proposed hypotheses, and results show (...) that: (1) Perceived negative workplace gossip adversely influences employees’ IRB and OCB. (2) Self-concept (OBSE and PIS) plays a mediating role in the relationship between perceived negative workplace gossip and employees’ behaviors (IRB and OCB). (3) Employees’ hostile attribution bias moderates the relationship between perceived negative workplace gossip and self-concept (OBSE and PIS); and also moderates the mediating effect of self-concept (OBSE and PIS) on the relationship between perceived negative workplace gossip and employees’ behaviors (IRB and OCB). Thus, our findings provide deeper insights into the potential harmful effects of gossip. In addition, we help to explain the underlying mechanism and boundary condition of these effects. (shrink)

The lymphatic vasculature plays a critical role in the regulation of body fluid volume and immune function. Extensive research into the molecular mechanisms that control blood vessel growth has led to identification of molecules that also regulate development and growth of the lymphatic vessels. This is generating a great deal of interest in the molecular control of the lymphatics in the context of embryogenesis, lymphatic disorders and tumor metastasis. Studies in animal models carried out over the past three years have (...) shown that the soluble protein growth factors, vascular endothelial growth factor (VEGF)‐C and VEGF‐D, and their cognate receptor tyrosine kinase, VEGF receptor‐3 (VEGFR‐3), are critical regulators of lymphangiogenesis. Furthermore, disfunction of VEGFR‐3 has recently been shown to cause lymphedema. The capacity to induce lymphangiogenesis by manipulation of the VEGF‐C/VEGF‐D/VEGFR‐3 signaling pathway offers new opportunities to understand the function of the lymphatic system and to develop novel treatments for lymphatic disorders. BioEssays 24:1030–1040, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

The Grätzer-Schmidt theorem of lattice theory states that each algebraic lattice is isomorphic to the congruence lattice of an algebra. We study the reverse mathematics of this theorem. We also show thatthe set of indices of computable lattices that are complete is Π11\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Pi ^1_1$$\end{document}-complete;the set of indices of computable lattices that are algebraic is Π11\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Pi ^1_1$$\end{document}-complete;the set of compact elements of a computable (...) lattice is Π11\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Pi ^{1}_{1}$$\end{document} and can be Π11\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Pi ^1_1$$\end{document}-complete; andthe set of compact elements of a distributive computable lattice is Π30\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Pi ^{0}_{3}$$\end{document}, and there is an algebraic distributive computable lattice such that the set of its compact elements is Π30\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Pi ^0_3$$\end{document}-complete. (shrink)