Dynamics of interacting Dicke model in a coupled-cavity array

We consider the dynamics of an array of mutually interacting cavities, each containing an ensemble of N two-level atoms. By exploring the possibilities offered by ensembles of various dimensions and a range of atom-light and photon-hopping values, we investigate the generation of multisite entanglement, as well as the performance of excitation transfer across the array, resulting from the competition between on-site nonlinearities of the matter-light interaction and intersite photon hopping. In particular, for a three-cavity interacting system it is observed that the initial excitation in the first cavity completely transfers to the ensemble in the third cavity through the hopping of photons between the adjacent cavities. Probabilities of the transfer of excitation of the cavity modes and ensembles exhibit characteristics of fast and slow oscillations governed by coupling and hopping parameters, respectively. In the large-hopping case, by seeding an initial excitation in the cavity at the center of the array, a tripartite W state, as well as a bipartite maximally entangled state, is obtained, depending on the interaction time. Population of the ensemble in a cavity has a positive impact on the rate of excitation transfer between the ensembles and their local cavity modes. In particular, for ensembles of five to seven atoms, tripartite W states can be produced even when the hopping rate is comparable to the cavity-atom coupling rate. A similar behavior of the transfer of excitation is observed for a four-coupled-cavity system with two initial excitations.

Experimental linear-optics simulation of multipartite non-locality in the ground state of a quantum Ising ring

Critical phenomena involve structural changes in the correlations of its constituents. Such changes can be reproduced and characterized in quantum simulators able to tackle medium-to-large-size systems. We demonstrate these concepts by engineering the ground state of a three-spin Ising ring by using a pair of entangled photons. The effect of a simulated magnetic field, leading to a critical modification of the correlations within the ring, is analysed by studying two- and three-spin entanglement. In particular, we connect the violation of a multipartite Bell inequality with the amount of tripartite entanglement in our ring.

Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces regulates DISC assembly

Death receptor activation triggers recruitment of FADD, which via its death effector domain (DED) engages the DEDs of procaspase 8 and its inhibitor FLIP to form death-inducing signalling complexes (DISCs). The DEDs of FADD, FLIP and procaspase 8 interact with one another using two binding surfaces defined by α1/α4 and α2/α5 helices, respectively. Here we report that FLIP has preferential affinity for the α1/α4 surface of FADD, whereas procaspase 8 has preferential affinity for FADD's α2/α5 surface. These relative affinities contribute to FLIP being recruited to the DISC at comparable levels to procaspase 8 despite lower cellular expression. Additional studies, including assessment of DISC stoichiometry and functional assays, suggest that following death receptor recruitment, the FADD DED preferentially engages FLIP using its α1/α4 surface and procaspase 8 using its α2/α5 surface; these tripartite intermediates then interact via the α1/α4 surface of FLIP DED1 and the α2/α5 surface of procaspase 8 DED2.

'When I Look I am Seen, So I Exist to Change': Supplementing Honneth's Recognition Model for Social Work

The subject of identity continues to attract widespread interest and debate in the social sciences. The nature of who we are, our potential to be different, and our similarity with others, underpins many present-day social issues. This paper contributes to this debate by examining critically the work of Axel Honneth on optimal identity-formation. Although broadly supporting Honneth’s chief construct of inter-personal recognition, a gap in his thinking is highlighted and addressed through proffering a fourth dimension to his tripartite model. This additional dimension requires demonstrations of recognition that instil hope in the face of hardship and empower positive transformations in identity. The implications of this reworked model for social work are then considered in terms of a range of approaches that can be utilised to build flourishing identities characterised by self-esteem, self-confidence, self-respect and self-belief.

Solitary and repetitive binding motifs for the AP2 complex alpha-appendage in amphiphysin and other accessory proteins

Adaptor protein (AP) complexes bind to transmembrane proteins destined for internalization and to membrane lipids, so linking cargo to the accessory internalization machinery. This machinery interacts with the appendage domains of APs, which have platform and beta-sandwich subdomains, forming the binding surfaces for interacting proteins. Proteins that interact with the subdomains do so via short motifs, usually found in regions of low structural complexity of the interacting proteins. So far, up to four motifs have been identified that bind to and partially compete for at least two sites on each of the appendage domains of the AP2 complex. Motifs in individual accessory proteins, their sequential arrangement into motif domains, and partial competition for binding sites on the appendage domains coordinate the formation of endocytic complexes in a temporal and spatial manner. In this work, we examine the dominant interaction sequence in amphiphysin, a synapse-enriched accessory protein, which generates membrane curvature and recruits the scission protein dynamin to the necks of coated pits, for the platform subdomain of the alpha-appendage. The motif domain of amphiphysin1 contains one copy of each of a DX(F/W) and FXDXF motif. We find that the FXDXF motif is the main determinant for the high affinity interaction with the alpha-adaptin appendage. We describe the optimal sequence of the FXDXF motif using thermodynamic and structural data and show how sequence variation controls the affinities of these motifs for the alpha-appendage.

Differential efficiency of the endocytic machinery in tonic and phasic synapses

Efficient synaptic vesicle membrane recycling is one of the key factors required to sustain neurotransmission. We investigated potential differences in the compensatory endocytic machineries in two glutamatergic synapses with phasic and tonic patterns of activity in the lamprey spinal cord. Post-embedding immunocytochemistry demonstrated that proteins involved in synaptic vesicle recycling, including dynamin, intersectin, and synapsin, occur at higher levels (labeling per vesicle) in tonic dorsal column synapses than in phasic reticulospinal synapses. Synaptic vesicle protein 2 occurred at similar levels in the two types of synapse. After challenging the synapses with high potassium stimulation for 30 min the vesicle pool in the tonic synapse was maintained at a normal level, while that in the phasic synapse was partly depleted along with expansion of the plasma membrane and accumulation of clathrin-coated intermediates at the periactive zone. Thus, our results indicate that an increased efficiency of the endocytic machinery in a synapse may be one of the factors underlying the ability to sustain neurotransmission at high rates.

A pre-embedding immunogold approach for detection of synaptic endocytic proteins in situ

During the past decade, many molecular components of clathrin-mediated endocytosis have been identified and proposed to play various hypothetical roles in the process [Nat. Rev. Neurosci. 1 (2000) 161; Nature 422 (2003) 37]. One limitation to the evaluation of these hypotheses is the efficiency and resolution of immunolocalization protocols currently in use. In order to facilitate the evaluation of these hypotheses and to understand more fully the molecular mechanisms of clathrin-mediated endocytosis, we have developed a protocol allowing enhanced and reliable subcellular immunolocalization of proteins in synaptic endocytic zones in situ. Synapses established by giant reticulospinal axons in lamprey are used as a model system for these experiments. These axons are unbranched and reach up to 80-100 microm in diameter. Synaptic active zones and surrounding endocytic zones are established on the surface of the axonal cylinder. To provide access for antibodies to the sites of synaptic vesicle recycling, axons are lightly fixed and cut along their longitudinal axis. To preserve the ultrastructure of the synaptic endocytic zone, antibodies are applied without the addition of detergents. Opened axons are incubated with primary antibodies, which are detected with secondary antibodies conjugated to gold particles. Specimens are then post-fixed and processed for electron microscopy. This approach allows preservation of the ultrastructure of the endocytic sites during immunolabeling procedures, while simultaneously achieving reliable immunogold detection of proteins on endocytic intermediates. To explore the utility of this approach, we have investigated the localization of a GTPase, dynamin, on clathrin-coated intermediates in the endocytic zone of the lamprey giant synapse. Using the present immunogold protocol, we confirm the presence of dynamin on late stage coated pits [Nature 422 (2003) 37] and also demonstrate that dynamin is recruited to the coat of endocytic intermediates from the very early stages of the clathrin coat formation. Thus, our experiments show that the current pre-embedding immunogold method is a useful experimental tool to study the molecular mechanisms of synaptic vesicle recycling.

Colocalization of synapsin and actin during synaptic vesicle recycling

It has been hypothesized that in the mature nerve terminal, interactions between synapsin and actin regulate the clustering of synaptic vesicles and the availability of vesicles for release during synaptic activity. Here, we have used immunogold electron microscopy to examine the subcellular localization of actin and synapsin in the giant synapse in lamprey at different states of synaptic activity. In agreement with earlier observations, in synapses at rest, synapsin immunoreactivity was preferentially localized to a portion of the vesicle cluster distal to the active zone. During synaptic activity, however, synapsin was detected in the pool of vesicles proximal to the active zone. In addition, actin and synapsin were found colocalized in a dynamic filamentous cytomatrix at the sites of synaptic vesicle recycling, endocytic zones. Synapsin immunolabeling was not associated with clathrin-coated intermediates but was found on vesicles that appeared to be recycling back to the cluster. Disruption of synapsin function by microinjection of antisynapsin antibodies resulted in a prominent reduction of the cytomatrix at endocytic zones of active synapses. Our data suggest that in addition to its known function in clustering of vesicles in the reserve pool, synapsin migrates from the synaptic vesicle cluster and participates in the organization of the actin-rich cytomatrix in the endocytic zone during synaptic activity.

Delivering a Research-Enabled Multistakeholder Partnership for Enhanced Patient Care at a Population Level: The Northern Ireland Comprehensive Cancer Program

The last 20 years have seen significant advances in cancer care in Northern Ireland, leading to measureable improvements in patient outcomes. Crucial to this transformation has been an ethos that recognizes the primacy role of research in effecting heath care change. The authors' model of a cross-sectoral partnership that unites patients, scientists, health care professionals, hospital trusts, bioindustry, and government agencies can be truly transformative, empowering tripartite clinical-academic-industry efforts that have already yielded significant benefit and will continue to inform strategy and its implementation going forward.

Schizophrenia risk from complex variation of complement component 4

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

Synaptic dysfunction in early encephalopathies : from genes to function

Tese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2015

Feminist epistemology meets the masculinity of marketing and consumer knowledge: a contemporary rendering of a decade-long debate

In this paper I outline possibilities for, and issues arising from, opposition towards the dominant ideologies and practices of marketing knowledge (Hirschman 1993) through an engagement with feminist epistemology (Longino 1991, Harding 1987). Feminist epistemology is a political branch of naturalised epistemology (Quine 1969) primarily concerned with critique of constructions of gender, gender norms and gendered interests within the production of knowledge (Anderson 1995) and with theorising, grounding and legitimating feminist knowledge making practices (Harding 1987). It is most often associated with the feminist critique of science, and with feminist science and technology studies (Haraway 1987, Wajman 1997). Feminist epistemology asks the question, ‘what is the nature of the feminist critical project as a way of knowing?’ (McLennan 1995:392). This paper outlines the basis of the feminist critique of knowledge generally, and as applied to marketing knowledge, offers description of the three main epistemological approaches to this question and suggestions for their application in practice. The paper progresses important work by consumer behaviour theorists (Bristor and Fischer 1993, Hirschman 1993) on the potentials of feminist ways of knowing for marketing and consumer behaviour by moving beyond the tripartite of feminist approaches outlined, and extending the discussion to take into account the development of situated knowledges theory (Haraway 1989, 1997), which has become so important in the decade since these papers were written. It joins ongoing conversations in consumer behaviour and marketing that share similar feminist concerns (Catterall et al 1997, 2000, 2005, Bettany and Woodruffe Burton 1999, 2005, and Hogg et al 1999, 2000) but in this contribution it takes a slightly tangential approach, seeing marketing knowledge in terms of its epistemic culture by using a model of masculinity in academic cultures from feminist theory (Wagner 1994) to help conceptualise it as such. The dominant masculine ideology of marketing knowledge both in execution (Penaloza 1994, Bristor and Fischer 1994, Fischer and Bristor 1993, Woodruffe 1996), and values (Hirschman 1993, Brown 2000, Desmond 1997) has been well documented over the past fifteen years. However, although the basis of this, how is it manifested and how a feminist informed marketing knowledge could be achieved, have been addressed somewhat in the literature (Bristor and Fischer 1993, Hogg, Bettany and Long 2000) an updated rendering is necessary which focuses specifically on epistemology and situates this discussion within a cultural framework. To do this I use the notions of cultural masculinity in academic disciplines developed by Wagner (1994) of ‘organisational egocentrism’, ‘fake collectivity’ and ‘de realisation’. With these, I raise important and specific issues around the notion of the masculinity of marketing knowledge, and then present an outline of feminist epistemologies to illustrate how different feminist approaches to knowledge would address these concerns.

Cappadocia: where Greek prepositions come to die

The Cappadocian variety of Ulaghátsh is unique among the Greek-speaking world in having lost the inherited preposition ‘se’. The innovation is found with both locative and allative uses and has af-ected both syntactic contexts in which ‘se’ was originally found, that is, as a simple preposition (1) and as the left-occurring member of circumpositions of the type ‘se’ + NP + spatial adverb (2). (1) a. tránse ci [to meidán] en ávʝa see.PST.3SG COMP ART.DEF.SG.ACC yard.SG.ACC COP.3 game.PL.NOM ‘he saw that in the yard is some game’ (Dawkins 1916: 348) b. ta erʝó da qardáʃa évɣan [to qonáq] ART.DEF.PL.NOM two ART.DEF.PL.NOM friend.PL.NOM ascend.PST.3PL ART.DEF.SG.ACC house.SG.ACC ‘the two friends went up to the house’ (Dawkins 1916: 354) (2) émi [ta qonáca mésa], kiríʃde [to ʝasdɯ́q píso] enter.PST.3SG ART.DEF.PL.NOM house.PL.ACC inside hide.PST.3SG. ART.DEF.SG.ACC cushion.SG.ACC behind ‘he went into the houses and hid behind the cushions’ (Dawkins 1916: 348) In this paper, we set out to provide (a) a diachronic account of the loss of ‘se’ in Asia Minor Greek, and (b) a synchronic analysis of its ramifications for the encoding of the semantic and grammatical functions it had prior to its loss. The diachronic development of ‘se’ is traced by comparing the Ulaghátsh data with those obtained from Cappadocian varieties that have neither lost it nor do they show signs of losing it and, crucially, also from varieties in which ‘se’ is in the process of being lost. The comparative analysis shows that the loss first became manifest in circumpositions in which ‘se’ was preposed to the complement to which in turn a wide range of adverbs expressing topological relations were postposed (émi sa qonáca mésa > émi ta qonáca mésa). This finding is accounted for in terms of Sinha and Kuteva’s (1995) distributed spatial semantics framework, which accepts that the elements involved in the constructions under investigation—the verb (émi), ‘se’ and the spatial adverb (mésa)—all contribute to the expression of the spatial relational meaning but with differences in weighting. Of the three, ‘eis’ made the most minimal contribution, the bulk of it being distributed over the verb and the adverb. This allowed for it to be optionally dropped from circumpositions, a stage attested in Phlo-tá Cappadocian and Silliot, and to be later completely abandoned, originally in allative and subsequently in locative contexts (earlier: évɣan so qonáq > évɣan to qonáq; later: so meidán en ávʝa > to meidán en ávʝa). The earlier loss in allative contexts is also dealt with in distributed semantics terms as verbs of motion such as έβγαν are semantically more loaded than vacuous verbs like the copula and therefore the preposition could be left out in the former context more easily than in the latter. The analysis also addresses the possibility that the loss of ‘se’ may ultimately originate in substandard forms of Medieval Greek, which according to Tachibana (1994) displayed SPATIAL ADVERB + NP constructions. Applying the semantic map model (Croft 2003, Haspelmath 2003), the synchronic analysis of the varieties that retain ‘se’ reveals that—like many other allative markers crosslinguistically—it displays a pattern of multifunctionality in expressing nine different functions (among others allative, locative, recipient, addressee, experiencer), which can be mapped against four domains, viz. the spatiotemporal, the social, the mental and the logicotextual (cf. Rice & Kabata 2007). In Ulaghátsh Cappadocian, none of these functions is overtly marked as such. In cases like (1), the intended spatial relational meaning is arrived at through the combination of the syntax and the inherent semantics of the verb and the zero-marked NP as well as from the context. In environments of the type exemplified by (2), the adverb contributes further to the correct interpretation. The analysis additionally shows that, despite the loss of ‘se’, Ulaghátsh patterns with all other Cappadocian varieties in one important aspect: Goal and Location are expressed similarly (by zero in Ulaghátsh, by ‘se’ in the other varieties) whereas Source is being kept distinct (expressed by ‘apó’ in all varieties). Goal-Location polysemy is very common across the world’s languages and, most crucially, prevails over other possible polysemies in the tripartite distinction Source—Location—Goal (Lestrade 2010, Nikitina 2009). Taking into account this empirical observation, our findings suggest that the reor-anisation of spatial systems can have a local effect—in our case the loss of a member of the prepositional paradigm—but will keep the original global picture intact, thus conforming to crosslinguistically robust tendencies.  References Croft, W. 2001. Radical Construction Grammar: Syntactic Theory in Typological Perspective. Oxford: Oxford University Press. Dawkins, R. M. 1916. Modern Greek in Asia Minor: A Study of the Dialects of Sílli, Cappadocia and Phárasa with Grammar, Texts, Translations and Glossary. Cambridge: Cambridge University Press. Haspelmath, M. 2003. The geometry of grammatical meaning: semantic maps and cross-linguistic comparison. In M. Tomasello (Ed.), The New Psychology of Language, Volume 2. New York: Erlbaum, 211–243. Lestrade, S. 2010. The Space of Case. Doctoral dissertation. Radboud University Nijmegen. Nikitina, T. 2009. Subcategorization pattern and lexical meaning of motion verbs: a study of the source/goal ambiguity. Linguistics 47, 1113–1141. Rice, S. & K. Kabata. 2007. Cross-linguistic grammaticalization patterns of the allative. Linguistic Typology 11, 451–514. Sinha, C. & T. Kuteva. 1995. Distributed spatial semantics. Nordic Journal of Linguistics 18:2, 167–199. Tachibana, T. 1994. Syntactic structure of spatial expressions in the “Late Byzantine Prose Alexander Romance”. Propylaia 6, 35–51.

Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors

The AMPA-receptor subunit GluA4 is expressed transiently in CA1 pyramidal neurons at the time synaptic connectivity is forming, but its physiological significance is unknown. Here we show that GluA4 expression is sufficient to alter the signaling requirements of long-term potentiation (LTP) and can fully explain the switch in the LTP kinase dependency from PKA to Ca2(+)/calmodulin-dependent protein kinase II during synapse maturation. At immature synapses, activation of PKA leads to a robust potentiation of AMPA-receptor function via the mobilization of GluA4. Analysis of GluA4-deficient mice indicates that this mechanism is critical for neonatal PKA-dependent LTP. Furthermore, lentiviral expression of GluA4 in CA1 neurons conferred a PKA-dependent synaptic potentiation and LTP regardless of the developmental stage. Thus, GluA4 defines the signaling requirements for LTP and silent synapse activation during a critical period of synapse development.

A sustentabilidade e o ciclo de vida dos edifícios

A crescente preocupação que envolve as questões ambientais a nível mundial, cada vez mais agravadas pelo comportamento irresponsável do Homem, conduziu à criação de métodos de avaliação dos impactes ambientais provocados por produtos e sistemas. Sendo o sector da construção responsável por grande parte desses impactes, é evidente a necessidade de aplicação de medidas que visem mitigar ou, no mínimo, reduzir até valores aceitáveis, essas agressões ao meio ambiente. Nesse âmbito, é natural que tenha surgido a ideia de aplicar uma metodologia tão precisa e rigorosa como a LCA ao sector da construção. No entanto, nos dias de hoje, as preocupações alargaram-se às vertentes social e económica que, juntamente com a vertente ambiental, formam o triângulo de equilíbrio do desenvolvimento sustentável. É precisamente essa avaliação tripartida que esta Dissertação pretende abordar, tentando aprofundar conhecimentos e fornecer alternativas, através da análise crítica, que possam contribuir para a melhoria contínua desta metodologia.