In vitro reconstitution assays are commonly used to study biological membrane fusion. However, to date, most ensemble and single‐vesicle experiments involving SNARE proteins have been performed only with lipid‐mixing, but not content‐mixing indicators. Through simultaneous detection of lipid and small content‐mixing indicators, we found that lipid mixing often occurs seconds prior to content mixing, or without any content mixing at all, during a 50‐seconds observation period, for Ca2+‐triggered fusion with SNAREs, full‐length synaptotagmin‐1, and complexin. Our results illustrate (...) the caveats of commonly used bulk lipid‐mixing fusion experiments. We recommend that proteoliposome fusion experiments should always employ content‐mixing indicators in addition to, or in place of, lipid‐mixing indicators. (shrink)

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)

Despite its biological importance, the mechanism of formation of cutin, the polymeric matrix of plant cuticles, has not yet been fully clarified. Here, for the first time, we show the participation in the process of lipid vesicles formed by the self‐assembly of endogenous polyhydroxy fatty acids. The accumulation and fusion of these vesicles (cutinsomes) at the outer part of epidermal cell wall is proposed as the mechanism for early cuticle formation. BioEssays 30:273–277, 2008. © 2008 Wiley Periodicals, Inc.

Synaptophysin (Syp) was the first synaptic vesicle (SV) protein to be cloned. Since its discovery in 1985, it has been used by us and by many laboratories around the world as an invaluable marker to study the distribution of synapses in the brain and to uncover the basic features of the life cycle of SVs. Although single gene ablation of Syp does not lead to an overt phenotype, a large body of experimental data both in vitro and in vivo (...) indicate that Syp (alone or in association with homologous proteins) is involved in multiple, important aspects of SV exo‐endocytosis, including regulation of SNARE assembly into the fusion core complex, formation of the fusion pore initiating neurotransmitter release, activation of SV endocytosis and SV biogenesis. In this article, we summarise the main results of the studies on Syp carried out by our and other laboratories, and explain why we believe that Syp plays a major role in SV trafficking. BioEssays 26:445–453, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The exocyst is a conserved octameric complex that physically tethers a vesicle to the plasma membrane, prior to membrane fusion. It is important not only for secretion and membrane delivery but also, in mammalian cells, for cytokinesis, ciliogenesis, autophagy, tumorigenesis, and host defense. The combination of genome editing and advanced light microscopy of exocyst subunits in living cells has recently shown the complex to be much more dynamic than previously appreciated, and exposed how little we still know about (...) its function and regulation. (shrink)

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor of ≈106. (...) This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs. (shrink)

Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different mechanisms. These (...) include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics. (shrink)

The origins and evolution of the Archaea, Bacteria, and Eukarya remain controversial. Phylogenomic‐wide studies of molecular features that are evolutionarily conserved, such as protein structural domains, suggest Archaea is the first domain of life to diversify from a stem line of descent. This line embodies the last universal common ancestor of cellular life. Here, we propose that ancestors of Euryarchaeota co‐evolved with those of Bacteria prior to the diversification of Eukarya. This co‐evolutionary scenario is supported by comparative genomic and phylogenomic (...) analyses of the distributions of fold families of domains in the proteomes of free‐living organisms, which show horizontal gene recruitments and informational process homologies. It also benefits from the molecular study of cell physiologies responsible for membrane phospholipids, methanogenesis, methane oxidation, cell division, gas vesicles, and the cell wall. Our theory however challenges popular cell fusion and two‐domain of life scenarios derived from sequence analysis, demanding phylogenetic reconciliation. (shrink)

Complex functions of the central nervous system such as learning and memory are believed to result from the modulation of the synaptic transmission between neurons. The sequence of events leading to the fusion of synaptic vesicles at the presynaptic active zone and the detection of this signal at the postsynaptic density involve the activity of ion channels and neurotransmitter receptors. Their accumulation and dynamic exchange at synapses are dependent on their interaction with synaptic scaffolds. These are synaptic structures composed (...) of adaptor proteins that provide binding sites for receptors and channels as well as other synaptic proteins. While in its entirety the synaptic scaffold is a relatively stable structure, individual adaptor proteins exchange at a fast time scale. These properties of scaffolds help to ensure the stability of synaptic transmission while permitting the modulation of synaptic strength. Here, we review the dynamics of the synaptic scaffold and of adaptor proteins in relation to their roles in the organisation of the synapse as well as in the clustering and trafficking of receptor proteins. BioEssays 30:1062–1074, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Cell communication plays a key role in multicellular organisms. In developing embryos as in adult organisms, cells communicate by coordinating their differentiation through the establishment and/or renewal of a variety of cell communication channels. Under both these conditions, cells interact by either receptor signalling, surface recognition of specific cell adhesion molecules or transfer of cytoplasmic components through junctional coupling. In recent years, it has become apparent that cells may also communicate through the extracellular release of microvesicles. They may originate as (...) either exosomes from the endosomal compartment upon fusion of multivesicular bodies with the plasma membrane or be shed directly from the plasma membrane via extensions of the cell surface. Microvesicles may disperse over long distances through body fluids and deliver their molecular cargo onto a variety of target cells. As a general rule, the metabolic fate of these cells is determined by the molecular nature of the vesicular cargo, while targeting itself depends on the affinity of the molecules expressed on the enclosing membrane. In this paper, we will be arguing that intercellular vesicular transfer is substantially different from other types of cell communication, allowing cells and molecules to interact on varying levels. Cells interacting via ligand signalling owe their specificity to the steric coupling with cognate receptor molecules. As such, it is a pure molecular process that affects target cells only upon integration into their responding repertoire. In this relationship, coupled cells are reciprocally adapted to each other through the selection of their respective signalling capacities, following exploration of their receptor specificity. Interaction by intercellular vesicles realizes a substantially different type of cell communication. Vesicular traffic allows donor cells to carry out a horizontal type of gene transfer and target this information over long distances via independently controlled mechanisms. Because of this independence, cells interacting via vesicular traffic are not expected to adapt their signalling correspondences, but to control instead the efficiency of their cargo delivery irrespective of the receptor repertoire expressed by the target tissue. In this paper, the multifaceted functions of the intercellular vesicular traffic will be discussed in a multilevel biosemiotic perspective with the aim of unravelling the cellular mechanisms devised by nature to accomplish communication. (shrink)

The chromosomes undergo a condensation‐decondensation cycle within the life cycle of mammalian cells. Chromosome condensation is a complex and critical event that is necessary for the equal distribution of genetic material between the two daughter cells. Although chromosome condensation‐decondensation and segregation is mechanistically complex, it proceeds with high fidelity during the eukaryotic cell division cycle. Cell fusion studies have indicated the presence of chromosome condensation factors in mammalian cells during mitosis. If extracts from mitotic cells are injected into immature (...) oocytes of Xenopus laevis, they induce meiotic maturation (i.e. germinal vesicle breakdown and chromosome condensation) within 2–3 hours. Recently, we showed that the maturation‐promoting activity of the mitotic cell extracts is inactivated by certain protein factors present in cells during the G1 period. The activity of the G1 factors coincides with the process of chromosome decondensation that begins at telophase and continues throughout the G1 period. These studies have revealed that the mitotic factors and the G1 factors play a pivotal role in the regulation of condensation and decondensation of chromosomes. Furthermore, our studies strongly suggest that nonhistone protein phosphorylation and dephosphorylation may mediate chromosome condensation and decondensation, respectively. (shrink)

SNAREs (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors) are a large family of proteins that are present on all organelles involved in intracellular vesicle trafficking and secretion. The interaction of complementary SNAREs found on opposing membranes presents an attractive lock‐and‐key mechanism, which may underlie the specificity of vesicle trafficking. Moreover, formation of the tight complex between a vesicle membrane SNARE and corresponding target membrane SNAREs could drive membrane fusion. In synapses, this tight complex, also referred to as (...) the synaptic core complex, is essential for neurotransmitter release. However, recent observations in knockout mice lacking major synaptic SNAREs challenge the prevailing notion on the executive role of these proteins in fusion and open up several questions about their exact role(s) in neurotransmitter release. Persistence of a form of regulated neurotransmitter release in these mutant mice also raises the possibility that other cognate or non‐cognate SNAREs may partially compensate for the loss of a particular SNARE. Future analysis of SNARE function in central synapses will also have implications for the role of these molecules in other vesicle trafficking events such as endocytosis and vesicle replenishment. Such analysis can provide a molecular basis for synaptic processes including certain forms of short‐term synaptic plasticity. BioEssays 24:926–936, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

A Paramecium cell has a stereotypically patterned surface, with regularly arranged cilia, dense‐core secretory vesicles and subplasmalemmal calcium stores. Less strikingly, there is also a patterning of molecules; for instance, some ion channels are restricted to certain regions of the cell surface. This design may explain very effective and selective responses, such as that to Ca2+ upon stimulation. It enables the cell to respond to a Ca2+ signal precisely secretion (exocytosis) or by changing its ciliary activity. These responses depend on (...) the location and/or type of signal, even though these two target structures co‐exist side‐by‐side, and normally only limited overlap occurs between the different functions. Furthermore, the patterning of exocytotic sites and the possibility of synchronous exocytosis induction in the sub‐second time range have considerably facilitated analyses, and thus led to new concepts of exocytotic membrane fusion. It has been possible to dissect complicated events like overlapping Ca2+ fluxes produced from external sources and from internal stores. Since molecular genetic approaches have become available for Paramecium, many different gene products have been identified only some of which are known from “higher” eukaryotes. Although a variety of basic cellular functions are briefly addressed to demonstrate the uniqueness of this unicellular organism, this article focuses on exocytosis regulation. BioEssays 24:649–658, 2002. © 2002 Wiley Periodicals, 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)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

Synaptic ribbons, the organelles identified in electron micrographs of the sensory synapses involved in vision, hearing, and balance, have long been hypothesized to play an important role in regulating presynaptic function because they associate with synaptic vesicles at the active zone. Their physiology and molecular composition have, however, remained largely unknown. Recently, a series of elegant studies spurred by technical innovation have finally begun to shed light on the ultrastructure and function of ribbon synapses. Electrical capacitance measurements have provided sub‐millisecond (...) resolution of exocytosis, evanescent‐wave microscopy has filmed the fusion of single 30 nm synaptic vesicles, electron tomography has revealed the 3D architecture of the synapse, and molecular cloning has begun to identify the proteins that make up ribbons. These results are consistent with the ribbon serving as a vesicle “conveyor belt” to resupply the active zone, and with the suggestion that ribbon and conventional chemical synapses have much in common. BioEssays 23:831–840, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

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

Increasing evidence indicates that extracellular vesicles (EVs) secreted from tumor cells play a key role in the overall progression of the disease state. EVs such as exosomes are secreted by a wide variety of cells and transport a varied population of proteins, lipids, DNA, and RNA species within the body. Gliomas constitute a significant proportion of all primary brain tumors and majority of brain malignancies. Glioblastoma multiforme (GBM) represents grade IV glioma and is associated with very poor prognosis despite the (...) cumulative advances in diagnostic procedures and treatment strategies. Here, the authors describe the progress in understanding the role of EVs, especially exosomes, in overall glioma progression, and how new research is unraveling the utilities of exosomes in glioma diagnostics and development of next‐generation therapeutic systems. Finally, based on an understanding of the latest scientific literature, a model for the possible working of therapeutic exosomes in glioma treatment is proposed. (shrink)

Once regarded as cellular ‘debris’ extracellular vesicles (EVs) emerge as one of the most intriguing entities in cancer pathogenesis. Intercellular trafficking of EVs challenges the notion of cancer cell autonomy, and highlights the multicellular nature of such fundamental processes as stem cell niche formation, tumour stroma generation, angiogenesis, inflammation or immunity. Recent studies reveal that intercellular exchange mediated by EVs runs deeper than expected, and includes molecules causative for cancer progression, such as oncogenes (epidermal growth factor receptor, Ras), and tumour (...) suppressors (PTEN). The uptake of oncogenic EVs (oncosomes) by various cells may profoundly change their biology, signalling patterns and gene expression, and in some cases cause their overt tumorigenic conversion. Moreover, EVs circulating in blood and present in body fluids provide an unprecedented access to the molecular circuitry driving cancer cells, and new technologies are being developed to exploit this property as a source of unique cancer biomarkers. (shrink)

No cure yet exists for devastating Alzheimer's disease (AD), despite many years and humongous efforts to find efficacious pharmacological treatments. So far, neither designing drugs to disaggregate amyloid plaques nor tackling solely inflammation turned out to be decisive. Mesenchymal stem cells (MSCs) and, in particular, extracellular vesicles (EVs) originating from them could be proposed as an alternative, strategic approach to attack the pathology. Indeed, MSC‐EVs—owing to their ability to deliver lipids/proteins/enzymes/microRNAs endowed with anti‐inflammatory, amyloid‐β degrading, and neurotrophic activities—may be exploited (...) as therapeutic tools to restore synaptic function, prevent neuronal death, and slow down memory impairment in AD. Herein the results presented in the most recently published studies on this topic are critically evaluated, providing a strong rationale for possible employment of MSC‐EVs in AD. (shrink)

Neurotransmitter release takes place by the exocytosis of loaded synaptic vesicles. The vesicles then fuse to the presynaptic membrane and are recycled by an endocytotic mechanism. A quantitative optical assay that detects uptake and release of a fluorescent dye during presynaptic activity was recently developed and used on the frog neauromuscular junction. I discuss a report(1) that demonstrates the effective application of this method to a Drosophila preparation. The authors use the shibire mutation and a spider venom to identify two (...) intermediates in vesicle recycling. Their report, along with other recent studies, demonstrates the power and promise of the genetic approach for the understanding of mechanisms of synapse function and development. (shrink)

I criticise a paper by Peter Forrest in which he argues that a principle of unrestricted countable fusion has paradoxical consequences. I argue that the paradoxical consequences that he exhibits may be due to his Whiteheadean assumptions about the nature of spacetime rather than to the principle of unrestricted countable fusion.

Fusion validity assessments employ structural equation models to investigate whether an existing scale functions in accordance with theory. Fusion validity parallels criterion validity by depending on correlations with non-scale variables but differs from criterion validity because it requires at least one theorized effect of the scale, and because both the scale and scaled-items are included in the model. Fusion validity, like construct validity, will be most informative if the scale is embedded in as full a substantive context (...) as theory permits. Appropriate scale functioning in a comprehensive theoretical context greatly enhances a scale’s validity. Inappropriate scale functioning questions the scale but the scale’s theoretical embedding encourages detailed diagnostic investigations potentially challenging specific items, the procedure used to calculate scale values, or aspects of the theory, but also possibly recommends incorporating additional items into the scale. The scaled items should have survived prior content and methodological assessments but the items may or may not reflect a common factor because items having diverse causal backgrounds can sometimes fuse to form a unidimensional entity. Though items reflecting a common cause can be assessed for fusion validity, we illustrate fusion validity in the more challenging context of a scale comprised of diverse items and embedded in a complicated theory. Specifically we consider the Leadership scale from the Alberta Context Tool with care aides working in Canadian long-term care homes. (shrink)

Two fusions can be in the same place at the same time. So long as a house made of Tinkertoys is intact, the fusion of all its Tinkertoys parts coincides with the fusion of it walls and its roof. If none of the Tinkertoys is destroyed, their fusion persists through the complete disassembly of the house. (So the house is not a fusion of its Tinkertoy parts.) The fusion of the walls and roof does not (...) persist through the complete disassembly because the walls and the roof themselves do not persist. (So the walls and the roof are also not fusions of their Tinkertoy parts.). (shrink)

Même si elle est emblématique de la pensée de Gadamer, la difficile notion d’une « fusion d’horizons » a été assez peu étudiée pour elle-même. Cet article se propose d’en faire ressortir le sens, la portée, mais aussi les difficultés. Il cherche surtout à montrer en quoi cette fusion d’horizons est l’œuvre du langage (lui-même pensé à partir de sa fusion avec l’être) et dans quelle mesure on peut y voir la version gadamérienne de l’adéquation entre l’être (...) et la pensée, suivant la conception classique de la vérité, que Gadamer ne renie jamais. (shrink)

Fusion is a well-known form of combining normal modal logics endowed with a Hilbert calculi and a Kripke semantics. Herein, fusion is studied over logic systems using sequent calculi labelled with truth values and with a semantics based on a two-sorted algebra allowing, in particular, the representation of general Kripke structures. A wide variety of logics, including non-classical logics like, for instance, modal logics and intuitionistic logic can be presented by logic systems of this kind. A categorical approach (...) of fusion is defined in the context of these logic systems. Preservation of soundness and completeness by fusion is studied. Soundness is preserved without further requirements, completeness is preserved under mild assumptions. (shrink)

The aim of this paper is to provide a proof-theoretic characterization of relevant logics including fusion and fission connectives, as well as Ackermann’s truth constant. We achieve this by employing the well-established methodology of labelled sequent calculi. After having introduced several systems, we will conduct a detailed proof-theoretic analysis, show a cut-admissibility theorem, and establish soundness and completeness. The paper ends with a discussion that contextualizes our current work within the broader landscape of the proof theory of relevant logics.

In this paper we introduce some fusion properties of forcing notions which guarantee that an iteration with supports of size ⩽κ not only does not collapse κ+ but also preserves the strength of κ. This provides a general theory covering the known cases of tree iterations which preserve large cardinals [3], Friedman and Halilović [5], Friedman and Honzik [6], Friedman and Magidor [8], Friedman and Zdomskyy [10], Honzik [12]).

We define the interpolative fusion T∪∗ of a family i∈I of first-order theories over a common reduct T∩, a notion that generalizes many examples of random or generic structures in the model-theo...

To obtain effective fusion results of multi source evidences with different importance, an evidence fusion method with importance discounting factors based on neutrosopic probability analysis in DSmT framework is proposed. First, the reasonable evidence sources are selected out based on the statistical analysis of the pignistic probability functions of single focal elements. Secondly, the neutrosophic probability analysis is conducted based on the similarities of the pignistic probability functions from the prior evidence knowledge of the reasonable evidence sources. Thirdly, (...) the importance discounting factors of the reasonable evidence sources are obtained based on the neutrosophic probability analysis and the reliability discounting factors of the real-time evidences are calculated based on probabilistic-based distances. Fourthly, the real-time evidences are discounted by the importance discounting factors and then the evidences with the mass assignments of neutrosophic empty sets are discounted by the reliability discounting factors. Finally, DSmT+PCR5 of importance discounted evidences is applied. Experimental examples show that the decision results based on the proposed fusion method are different from the results based on the existed fusion methods. Simulation experiments of recognition fusion are performed and the superiority of proposed method is testified well by the simulation results. (shrink)

We have been invited to contribute a short assessment of Levine's response to Siderits’ position in the emerging debate between "fusion philosophy" and "comparative philosophy." Perhaps a brief word is in order regarding our backgrounds: Michael Nylan is a student of early China, with strong inter-disciplinary training and interests, who has attempted work in both philosophy and translation. Martin Verhoeven is a historian by training, a translator by avocation, and a Buddhist practitioner. Both of us have committed ourselves for (...) decades to past traditions that can only be accessed through classical Chinese language, and that surely colors our views. At the same time, those views are not identical, but stereophonic. (shrink)

The paper provides a new and detailed critique of Barker and Dowe’s argument against multi-location. This critique is not only novel but also less committal than previous ones in the literature in that it does not require hefty metaphysical assumptions. The paper also provides an analysis of some metaphysical relations between mereological and locational principles.

This article aims to explore two different but interrelated problems. The first objective, the more abstract one, is to discuss the plausibility of fusionism as a theoretical project of bridging the philosophical gap between libertarianism and free-market conservatism. Our thesis is that while fusionism could succeed, as a strategic alliance, in promoting specific policies, the differences between libertarianism and conservatism are irreconcilable at the level of fundamental intellectual assumptions. More precisely, starting from Hayek’s objections to conservatism, we argue that the (...) crucial divide is that between two conceptions about the prerequisites for social order. The second objective is to show how the differences between the policy prescriptions endorsed by conservatives and libertarians within the Tea Party (mainly with regard to religion-related issues) are illustrative for the theoretical point defended in the first sections. (shrink)

There are two main ways in which the notion of mereological fusion is usually defined in the current literature in mereology which have been labelled ‘Leśniewski fusion’ and ‘Goodman fusion’. It is well-known that, with Minimal Mereology as the background theory, every Leśniewski fusion also qualifies as a Goodman fusion. However, the converse does not hold unless stronger mereological principles are assumed. In this paper I will discuss how the gap between the two notions can (...) be filled, focussing in particular on two specific sets of principles that appear to be of particular philosophical interest. The first way to make the two notions equivalent can be used to shed some interesting light on the kind of intuition both notions seem to articulate. The second shows the importance of a little-known mereological principle which I will call ‘Mild Supplementation’. As I will show, the mereology obtained by adding Mild Supplementation to Minimal Mereology occupies an interesting position in the landscape of theories that are stronger than Minimal Mereology but weaker than what Achille Varzi and Roberto Casati have labelled ‘Extensional Mereology’. (shrink)

We tested whether cognitive fusion impairs emotion differentiation and thereby mediates relations between cognitive fusion and depression and panic symptoms among 55 adults, 50.9% women). Using visual stimuli, we elicited multiple emotion states and measured emotional intensity – the subjective emotion intensity of elicited emotions, as well as emotional differentiation – the degree of co-activation of multiple negative emotions when a specific emotion was elicited. First, as hypothesised, we found that cognitive fusion predicted lower levels of emotion (...) differentiation. In contrast, as hypothesised, these effects were significantly greater than the effects of cognitive fusion on emotion intensity. Second, as predicted, MECA, but not SEI, predicted depression and panic symptoms. Finally, we found that MECA mediated the effects of cognitive fusion on depression and panic symptoms. The present findings contribute novel, preliminary empirical insight into associations between cognitive fusion, impaired emotion differentiation and mental ill-health. (shrink)

fusion theory challenges efforts to see theory as inhibiting by presenting an approach that is innovative, eclectic, and subtle in order to draw out competing and constellating ideas and opinions. This collected volume of essays examines fusion theory and demonstrates how the theory can be applied to the reading of various works of Indian English novelists.

I use the concept of epistemic injustice to think through the practice and methodology of comparative, or “fusion,” philosophy. I make two related claims: 1) the philosophical ethnocentrism displayed by academic departments in the U.S. is a case of epistemic injustice, primarily willful ignorance, that ought to be rectified; 2) the corrective to this problem, namely, fusion philosophy, is itself epistemically problematic in its tendency toward ontological expansiveness, that is, an unjustified claim to all traditions as one’s own. (...) In the end, I hope to show how a robust practice of self-reflexivity can counter this potentially colonizing tendency of fusion philosophizing. (shrink)

Logics of part/whole relations frequently take parthood or proper parthood as primitive, defining the remaining mereological properties and relations in terms of them. I argue from considerations involving Weak Supplementation for the conclusion that we should take fusion as our mereological primitive. I point out that the intuitions supporting Weak Supplementation also support a stronger principle, Weak Supplementation of Pluralities, and that the principle can only do the work demanded by our intuitions when formulated in terms of a notion (...) of fusion that cannot be defined merely in terms of mereological properties and relations, logic, and a membership relation. So, insofar as we think any definition of fusion must be so restricted, we have motivation to take fusion as primitive; further, we have greater insight into the motivation for our supplementation principle and which version of that principle we ought to endorse. (shrink)

This paper explores a case example of qualitative research that applied productive hermeneutics and the central concept, fusion of horizons. Interpretation of meaning is a fusing of the researchers’ and subjects’ perspectives and serves to expand understanding. The purpose is to illustrate an exemplar of qualitative research without establishing a rigid recipe of methodology. The illustration is based on in-depth observational and textual data from an applied anthropological study conducted in western Alaska with Yup’ik hunters and fishers and government (...) agency employees as they worked towards collaborative management. The metaphor of the hermeneutical circle is showcased to help the reader understand the philosophical underpinnings and the analytical processes used to realize a meaningful interpretation. A series of organizing systems for the interpretation is described, culminating in a final organizing system to communicate a fully realized understanding of collaborative management at the time. (shrink)

Generalising Hrushovski's fusion technique we construct the free fusion of two strongly minimal theories T₁, T₂ intersecting in a totally categorical sub-theory T₀. We show that if, e.g., T₀ is the theory of infinite vector spaces over a finite field then the fusion theory Tω exists, is complete and ω-stable of rank ω. We give a detailed geometrical analysis of Tω, proving that if both T₁, T₂ are 1-based then, Tω can be collapsed into a strongly minimal (...) theory, if some additional technical conditions hold—all trivially satisfied if T₀ is the theory of infinite vector spaces over a finite field Fq. (shrink)

fusion theory challenges efforts to see theory as inhibiting by presenting an approach that is innovative, eclectic, and subtle in order to draw out competing and constellating ideas and opinions. This collected volume of essays examines fusion theory and demonstrates how the theory can be applied to the reading of various works of Indian English novelists.

In “Tropes and Ordinary Physical Objects”, Kris McDaniel argues that ordinary physical objects are fusions of monadic and polyadic tropes. McDaniel calls his view “TOPO”—for “Theory of Ordinary Physical Objects”. He argues that we should accept TOPO because of the philosophical work that it allows us to do. Among other things, TOPO is supposed to allow endurantists to reply to Mark Heller’s argument for perdurantism. But, we argue in this paper, TOPO does not help endurantists do that; indeed, we argue (...) that anyone who accepts TOPO should reject endurantism. (shrink)

‘Fusion’ is a philosophical term of art, with a variety of uses. First, it is often a synonym for ‘sum’. In this sense, a is a fusion of b, c and d iff b, c and d are parts of a, and every part of a shares a part with b, c or d. So a cat is a fusion of the cells which compose it, and the same cat is a fusion of the molecules which (...) compose it. Relatedly, ‘fusion’ can refer to the occurrence of such composition: philosophers disagree about whether fusion is widespread, about whether it can be a vague matter, and so on. (shrink)

Remarkable advances in cold fusion, known also as LENR, raised the hope for a safer and cheaper nuclear energy. The results, however, cannot be explained from the point of view of current physical understanding of nuclear fusion. This is an obstacle for research investment in this field. The present book suggests a new approach for analysis of the experimental results and practical recommendations based on the models of atomic nuclei derived in the BSM-Supergravitation Unified theory (BSM-SG). The book (...) provides: (1) a method for analysis of the LENR experiments using the BSM-SG atomic models; (b) a selection of isotopes suitable for a more efficient energy yield with a minimum of radioactive byproducts; (c) practical considerations for selection of the technical method and the reaction environment. (shrink)

The question whether the fusion of the musical traditions of different cultures is a good thing or not is irrelevant in practical terms, since there is no realistic possibility of preventing it, but the advantages and disadvantages that the process brings are worth considering nevertheless. The loss of diversity that results when one tradition is overwhelmed by its contact with a more influential one is not redressed by the increased variety that comes about within the dominant tradition, since the (...) latter are variations within a tradition rather than traditions of distinct origins. But the common denominator that allows different traditions to interact meaningfully with one another points to the ability of music to bring us in touch with our common humanity. (shrink)

We introduce a new operator – belief fusion– which aggregates the beliefs of two agents, each informed by a subset of sources ranked by reliability. In the process we definepedigreed belief states, which enrich standard belief states with the source of each piece of information. We note that the fusion operator satisfies the invariants of idempotence, associativity, and commutativity. As a result, it can be iterated without difficulty. We also define belief diffusion; whereas fusion generally produces a (...) belief state with more information than is possessed by either of its two arguments, diffusion produces a state with less information. Fusion and diffusion are symmetric operators, and together define a distributive lattice. Finally, we show that AGM revision can be viewed as fusion between a novice and an expert. (shrink)

Some people have stressed that there is a close analogy between meaning experiences, i.e., experiences as of understanding concerning linguistic expressions, and seeing-in experiences, i.e., pictorial experiences of discerning a certain item – what a certain picture presents, viz. the picture’s subject – in another item – the picture’s vehicle, the picture’s physical basis. Both can be seen as fusion experiences, in the minimal sense that they are experiential wholes made up of different aspects. Actually, two important similarities between (...) such experiences may lead one to think that they are experiences of the same type. In this paper, however, I will try to show that notwithstanding such similarities, these experiences are typologically different. For there are two dissimilarities between such experiences that are more relevant on this typological concern than their similarities. Indeed, unlike meaning experiences, seeing-in experiences are first of all recognitional experiences of a sort that makes them perceptual experiences as well. Moreover, again unlike meaning experiences, seeing-in experiences are fusion experiences in the substantial sense that the experiential whole is more than the sum of its experiential parts taken in isolation, for when such parts figure in that whole, they interact with each other. In a nutshell, unlike meaning experiences, seeing-in experiences are proper fusion experiences. (shrink)

This article shows that although Fitch’s paradox has been extremely widely studied, up to now no correct formalization of the problem has been proposed. The purpose of this article is to present the paradox front the viewpoint of combining logics. It is argued that the correct minimal logic to state the paradox is composed by a fusion of modal frames, and a fusion of modal languages and logics.

We examined the influence of identity fusion and status of evaluator on willingness to fight for one’s group after group-descriptive or not group-descriptive feedback. The valence of evaluative information was varied as well: feedback either support negative group-stereotype or contradict negative group-stereotype. In two studies we partially replicated previous findings on self-verification. Individuals fused with one’s group were more prone than non fused to fight for group members after receiving, challenging, not group-describing feedback, but only when evaluator’s status was (...) high. When the evaluator’ status was low, fused participants engaged in self-enhancement strategies: that is they endorse radical behavior after negative, even if group-describing, feedback. We discuss the importance of identity fusion and evaluator’s status for determining when self-enhancement and self-verification will and will not be evoke. (shrink)