Mapping cosmopolis: moral topographies of the medieval city

Cosmopolis is a concept that has a long history in many cultures around the globe. It is a mirroring of the 'social' and 'natural' worlds, such that in one is seen the order and the structures of the other -- a mutual 'mapping'. In this paper I examine how the presence of cosmopolis -- a Christianised cosmopolis of the European Middle Ages -- was made evident in the representation and formation of cities at that time. I reveal a dualism between the social and spatial ordering of both city and cosmos which defined and reinforced social and spatial boundaries in urban landscapes, evident for example in the 11th and 12th centuries. Recently, Toulmin (1992) has taken the idea of cosmopolis to argue that it has been a persistent presence in Western - Enlightenment science, philosophy, and religion -- a 'hidden agenda of modernity'. I contend that, as an idea, cosmopolis has a much earlier circulation in European thinking, not least in the Middle Ages. Locating cosmopolis in the medieval and the modern periods then begs a question of what is it that really makes the two distinct and separate? All too often human geographers have emphasised discontinuities between the 'medieval' and 'modern' age, locating the 'rise of modernity' some time in the Enlightenment period. However, what 'mapping' cosmopolis reveals are continuities, binding time and space together, which when looked at begin to help query the modernity concept itself.

Technology and the architecture of markets: re-configuring the Canadian equity market

This paper examines the relation between technical possibilities, liberal logics, and the concrete reconfiguration of markets. It focuses on the enrolling of innovations in communication and information technologies into the markets traditionally dominated by stock exchanges. With the development of capacities to trade on-screen, the power of incumbent market makers has been challenged as a less stable array of competing quasi-public and private marketplaces emerges. Developing a case study of the Toronto Stock Exchange, I argue that narrative emphasis on the performative power of sociotechnical innovations, the deterritorialisation of financial relations, and the erosion of state capacities needs qualification. A case is made for the importance of developing an understanding of: the spaces of encounter between emerging social technologies and property rights, rules of exchange, and structures of governance; and the interplay of orderings of different institutional composition and spatial reach in the reconfiguration of market architectures. Only then can a better grasp be gained of the evolving dynamics between making markets, the regulatory powers of the state, and their delimitations.

CD33 reponses are blocked by SOCS3 through accelerated proteasomal-mediated turnover

CD33 is a member of the sialic acid–binding immunoglobulin-like lectin (Siglec) family of inhibitory receptors and a therapeutic target for acute myeloid leukemia (AML). CD33 contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM), which can recruit SHP-1 and SHP-2. How CD33 expression is regulated is unclear. Suppressor of cytokine signaling 3 (SOCS3) is expressed in response to cytokines, LPS, and other PAMPs, and competes with SHP-1/2 binding to ITIMs of cytokine receptors, thereby inhibiting signaling. In this study, using peptide pull-down experiments, we found that SOCS3 can specifically bind to the phosphorylated ITIM of CD33. Additionally, following cross-linking SOCS3 can recruit the ECS E3 ligase resulting in accelerated proteasomal degradation of both CD33 and SOCS3. Our data suggest that the tyrosine motifs in CD33 are not important for internalization, while they are required for degradation. Moreover, SOCS3 inhibited the CD33-induced block on cytokine-induced proliferation. This is the first receptor shown to be degraded by SOCS3 and where SOCS3 and its target protein are degraded concomitantly. Our findings clearly suggest that during an inflammatory response, the inhibitory receptor CD33 is lost by this mechanism. Moreover, this has important clinical implications as tumors expressing SOCS3 may be refractory to -CD33 therapy.

Reparation or retribution: an investigation into regulatory compliance in planning

It is an axiom of good planning practice that procedure is informed by up-to-date research. Consequently, it is surprising to discover that there remains a dearth of specialised planning-enforcement literature relating to theory and implementation. In this paper an evaluation is given of the effectiveness of planning enforcement in Britain by reviewing existing legislative mechanisms and strategies employed by officials. Theoretical perspectives are drawn upon to suggest how the system might be improved through attention to the structural factors underpinning it.

Information used in detecting upcoming collisions.

In four experiments we examined the nature of the information used in judging whether events would or would not give rise to a collision in the near future. Observers were tested in situations depicting approaches between two objects (lateral approaches) and approaches between an object and the point of observation (head-on approaches), with objects moving according to constant deceleration or sinusoidal deceleration patterns. Judgments were found to be based, to a large extent, on the (in)sufficiency of current deceleration to avoid upcoming collision, as specified optically by tau-dot (tau over dot). However, the information specified, by tau (tau), that is the current (first-order) time remaining until contact, was also found to play a significant role. We deduce that judgment of upcoming collision is based on the detection Of T and its evolution over time, suggesting that observers are sensitive to Deltatau rather than to tau over dot itself.

Zipf and Type-Token rules for the English, Spanish, Irish and Latin languages

The Zipf curves of log of frequency against log of rank for a large English corpus of 500 million word tokens, 689,000 word types and for a large Spanish corpus of 16 million word tokens, 139,000 word types are shown to have the usual slope close to –1 for rank less than 5,000, but then for a higher rank they turn to give a slope close to –2. This is apparently mainly due to foreign words and place names. Other Zipf curves for highlyinflected Indo-European languages, Irish and ancient Latin, are also given. Because of the larger number of word types per lemma, they remain flatter than the English curve maintaining a slope of –1 until turning points of about ranks 30,000 for Irish and 10,000 for Latin. A formula which calculates the number of tokens given the number of types is derived in terms of the rank at the turning point, 5,000 for both English and Spanish, 30,000 for Irish and 10,000 for Latin.

The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5'-to-3' polarity.

The human coronavirus 229E replicase gene encodes a protein, p66HEL, that contains a putative zinc finger structure linked to a putative superfamily (SF) 1 helicase. A histidine-tagged form of this protein, HEL, was expressed using baculovirus vectors in insect cells. The purified recombinant protein had in vitro ATPase activity that was strongly stimulated by poly(U), poly(dT), poly(C), and poly(dA), but not by poly(G). The recombinant protein also had both RNA and DNA duplex-unwinding activities with 5'-to-3' polarity. The DNA helicase activity of the enzyme preferentially unwound 5'-oligopyrimidine-tailed, partial-duplex substrates and required a tail length of at least 10 nucleotides for effective unwinding. The combined data suggest that the coronaviral SF1 helicase functionally differs from the previously characterized RNA virus SF2 helicases.

Cell surface beta 1, 4-galactosyltransferase 1 promotes apoptosis by inhibiting epidermal growth factor receptor pathway.

Our previous studies have shown that overexpression of beta1,4-galactosyltransferase1 (beta1,4GT1) leads to increased apoptosis induced by cycloheximide (CHX) in SMMC-7721 human hepatocarcinoma cells. However, the role of beta1,4GT1 in apoptosis remains unclear. Here we demonstrated that cell surface beta1,4GT1 inhibited the autophosphorylation of epidermal growth factor receptor (EGFR) especially at Try 1068. The phosphorylation of protein kinase B (PKB/Akt) and extracellular signal-regulated protein kinase1/2 (ERK1/2), which are downstream molecules of EGFR, were also reduced in cell surface beta1,4GT1-overexpressing cells. Furthermore, the translocations of Bad and Bax that are regulated by PKB/Akt and ERK1/2 were also increased in these cells. As a result, the release of cytochrome c from mitochondria to cytosol was increased and caspase-3 was activated. In contrast, RNAi-mediated knockdown of beta1,4GT1 increased the autophosphorylation of EGFR. These results demonstrated that cell surface beta1,4GT1 may negatively regulate cell survival possibly through inhibiting and modulating EGFR signaling pathway.

Using choice experiments to explore the spatial distribution of willingness to pay for rural landscape improvements

We report findings from a choice experiment survey designed to estimate the economic benefits of policy measures to improve the rural landscape in the Republic of Ireland. Using a panel mixed logit specification to account for unobserved taste heterogeneity we derived individual-specific willingness-to-pay (WTP) estimates for each respondent in the sample. We subsequently investigated the spatial dependence of these estimates. Results suggest the existence of positive spatial autocorrelation for all rural landscape attributes. As a means of benefit transfer, kriging methods were employed to interpolate WTP estimates across the whole of the Republic of Ireland. The kriged WTP surfaces confirm the existence of spatial dependence and illustrate the implied spatial variation and regional disparities in WTP for all the rural landscape improvements investigated.

Are Northern Ireland’s communities dividing? Evidence from geographically consistent Census of Population data, 1971–2001

There is an extensive literature on various aspects of segregation in Northern Ireland (NI). However, there are no census-based analyses of population change and residential segregation that cover the entire 1971 – 2001 period using consistent geographical units through time for all NI. This shortcoming is addressed in this paper by an analysis of changes in (ihs1) the spatial distribution of population and (iihs1) residential segregation between 1971 and 2001 using the NI Grid-Square Product comprising data for a set of 1 rm km2 cells that cover all populated areas in NI. The substantive issue of whether NI has become more segregated through time is addressed as are questions about measuring change through time using the census and the importance of spatial scale. One important conclusion is that NI indeed became more residentially segregated between 1971 and 2001, but that residential segregation in 2001 remained approximately at its 1991 level according to most indicators.

The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognition.

T cell immune responses to central nervous system-derived and other self-antigens are commonly described in both healthy and autoimmune individuals. However, in the case of the human prion protein (PrP), it has been argued that immunologic tolerance is uncommonly robust. Although development of an effective vaccine for prion disease requires breaking of tolerance to PrP, the extent of immune tolerance to PrP and the identity of immunodominant regions of the protein have not previously been determined in humans. We analyzed PrP T cell epitopes both by using a predictive algorithm and by measuring functional immune responses from healthy donors. Interestingly, clusters of epitopes were focused around the area of the polymorphic residue 129, previously identified as an indicator of susceptibility to prion disease, and in the C-terminal region. Moreover, responses were seen to PrP peptide 121-134 containing methionine at position 129, whereas PrP 121-134 [129V] was not immunogenic. The residue 129 polymorphism was also associated with distinct patterns of cytokine response: PrP 128-141 [129M] inducing IL-4 and IL-6 production, which was not seen in response to PrP 128-141 [129V]. Our data suggest that the immunogenic regions of human PrP lie between residue 107 and the C-terminus and that, like with many other central nervous system antigens, healthy individuals carry responses to PrP within the T cell repertoire and yet do not experience deleterious autoimmune reactions.