Organization of mammary epithelial cells into 3D acinar structures requires glucocorticoid and JNK signaling

Mammary epithelial cells cultured on a concentrated laminin-rich extracellular matrix formed 3D acinar structures that matured to polarized monolayers surrounding a lumen. In the absence of glucocorticoids mature acinus formation failed and the expression of an acinus-associated, activator protein 1 (AP1) and nuclear factor kappaB transcription factor DNA-binding profile was lost. Treatment with the JNK inhibitor, SP600125, caused similar effects, whereas normal organization of the mammary epithelial cells as acini caused JNK activation in a glucocorticoid-dependent manner. The forming acini expressed BRCA1, GADD45beta, MEKK4, and the JNK activating complex GADD 45beta-MEKK4 in a glucocorticoid-dependent fashion. JNK catalyzed phosphorylation of c-Jun was also detected in the acini. In addition, expression of beta4 integrin and in situ occupation of its promoter by AP1 components, c-Jun and Fos, was glucocorticoid dependent. These results suggest that glucocortocoid signaling regulates acinar integrity through a pathway involving JNK regulation of AP1 transcription factors and beta4 integrin expression.

High-affinity NO(3-)-H+ cotransport in the fungus Neurospora:induction and control by pH and membrane voltage

High-affinity nitrate transport was examined in intact hyphae of Neurospora crassa using electrophysiological recordings to characterize the response of the plasma membrane to NO3- challenge and to quantify transport activity. The NO3(-)-associated membrane current was determined using a three electrode voltage clamp to bring membrane voltage under experimental control and to compensate for current dissipation along the longitudinal cell axis. Nitrate transport was evident in hyphae transferred to NO3(-)-free, N-limited medium for 15 hr, and in hyphae grown in the absence of a nitrogen source after a single 2-min exposure to 100 microM NO3-. In the latter, induction showed a latency of 40-80 min and rose in scalar fashion with full transport activity measurable approx. 100 min after first exposure to NO3-; it was marked by the appearance of a pronounced sensitivity of membrane voltage to extracellular NO3- additions which, after induction, resulted in reversible membrane depolarizations of (+)54-85 mV in the presence of 50 microM NO3-; and it was suppressed when NH4+ was present during the first, inductive exposure to NO3-. Voltage clamp measurements carried out immediately before and following NO3- additions showed that the NO3(-)-evoked depolarizations were the consequence of an inward-directed current that appeared in parallel with the depolarizations across the entire range of accessible voltages (-400 to +100 mV). Measurements of NO3- uptake using NO3(-)-selective macroelectrodes indicated a charge stoichiometry for NO3- transport of 1(+):1(NO3-) with common K(m) and Jmax values around 25 microM and 75 pmol NO3- cm-2sec-1, respectively, and combined measurements of pHo and [NO3-]o showed a net uptake of approx. 1 H+ with each NO3- anion. Analysis of the NO3- current demonstrated a pronounced voltage sensitivity within the normal physiological range between -300 and -100 mV as well as interactions between the kinetic parameters of membrane voltage, pHo and [NO3-]o. Increasing the bathing pH from 5.5 to 8.0 reduced the current and the associated membrane depolarizations 2- to 4-fold. At a constant pHo of 6.1, driving the membrane voltage from -350 to -150 mV resulted in an approx. 3-fold reduction in the maximum current and a 5-fold rise in the apparent affinity for NO3-. By contrast, the same depolarization effected an approx. 20% fall in the K(m) for transport as a function in [H+]o. These, and additional results are consistent with a charge-coupling stoichiometry of 2(H+) per NO3- anion transported across the membrane, and implicate a carrier cycle in which NO3- binding is kinetically adjacent to the rate-limiting step of membrane charge transit. The data concur with previous studies demonstrating a pronounced voltage-dependence to high-affinity NO3- transport system in Arabidopsis, and underline the importance of voltage as a kinetic factor controlling NO3- transport; finally, they distinguish metabolite repression of NO3- transport induction from its sensitivity to metabolic blockade and competition with the uptake of other substrates that draw on membrane voltage as a kinetic substrate.

Persistent income poverty and deprivation in the European Union: An analysis of the first three waves of the European Community Household Panel

Poverty research has increasingly focused on persistent income poverty, both as a crucial social indicator and as a target for policy intervention. Such an approach can lead to an identification of a sub-set of poor individuals facing particularly adverse circumstances and/or distinctive problems in escaping from poverty. Here we seek to establish whether, in comparison with cross-sectional measures, persistent poverty measures also provide a better measure of exclusion from a minimally acceptable way of life and relate with other important variables in a logical fashion. Our analysis draws upon the first three waves of the ECHP and shows that a persistent poverty measure does constitute a significant improvement over its cross-sectional counterpart in the explanation of levels of deprivation. Persistent poverty is related to life-style deprivation in a manner that comes close to being uniform across countries. The measure of persistence also conforms to our expectations of how a poverty measure should behave in that, unlike relative income poverty lines, defining the threshold level more stringently enables us to identify progressively groups of increasingly deprived respondents. Overall the persistent poverty measure constitutes a significant advance on cross-sectional income measures. However, there is clearly a great deal relating to the process of accumulation and of erosion of resources, which is not fully captured in the persistent poverty measure. In the absence of such information, there is a great deal to be said for making use of both types of indictors in formulating and evaluating policies while we continue to improve our understanding of longer-term processes.

Multiple deprivation and persistent poverty in the European Union

The literature on Social exclusion has focused attention on the processes leading to exposure to multiple disadvantage. Despite the influence this perspective has had on both academic and policy discussions, conceptual analysis has remained imprecise and empirical evidence modest. We have made use of the European Community Household Panel (ECHP) in order to examine the extent to which persistent income poverty results in multiple deprivation. Our analysis shows that only a modest proportion of the persistently poor can he characterized as being exposed to such deprivation. While persistent poverty and multiple deprivation combine to produce extremely high levels of economic strain, there is no evidence that they interact in a significant fashion. We argue that understanding deprivation is not facilitated by focusing on a cleavage between a multiply deprived minority and a comfortable majority, and we consider the policy implications of this argument.

SOCIAL-CLASS, CLASS ORIGINS AND POLITICAL PARTISANSHIP IN THE REPUBLIC-OF-IRELAND

As Laver (1992) notes, people who write about Irish politics frequently describe Ireland as a rather peculiar place. One aspect of this peculiarity is that voters in the Republic of Ireland do not behave like their European counterparts. In particular, Irish voting patterns appear to be only weakly structured by social class. Recent contributions to the debate employing a more sophisticated categorisation of classes have led to some qualification of the 'politics without social bases' description, but still lead to the broad conclusion that any relationship which does exist between social divisions, on the one hand, and party preference, on the other, is, at most, quite marginal. In this paper we draw on data from the 1990 European Values Study to re-examine this issue. We apply a variety of models to the data, including logit regression and diagonal reference models (Sobel 1981, 1984) to explore the complex fashion in which class and political preferences are related in Ireland. We argue that the relationship between such preferences and social divisions are, in fact, greater than has been hitherto thought. In particular, we show the importance of taking into account not only social class but also class origins and class mobility in understanding the nature of political partisanship in the Republic of Ireland.

The Casual Buttress:Certainty and Contingency in the Study of the Vernacular

Impromptu accretions such as the buttresses in Robin Walkers photograph are moments that are familiar in the architecture of the everyday. Indeed the buttress is a very common occurrence with these cottages in particular, their mud walls being poor at resisting concentrated lateral loading. While not always required the buttress emerges when requirements to create spaces to support inhabitation are at odds with the external form and construction of the buildings. These points of disjunction are resolved in an additive fashion externally. The location varies from structure to structure, occasionally the buttress is be used as a point of connection for further structures, becoming subsumed in outbuildings or walls. This preponderance to variety means that it is omitted from the reductive drawings of type that classify these buildings and yet it occurs in enough for it to have a fundamental and transformative relationship to the generality of cottages.
What is of interest is not so much what these structures hold in common, but rather what differentiates them. It is their capacity for variety within a defined range which allows them at once to speak at once of broader social structures and of a specific place and person.
Using the above observation this paper treats of the failure of architectural typological studies of the vernacular to derive anything other than formal exemplars, and posits an alternative approach based on a focus on the technical construction of such buildings.

Web Services and Incerta Spiriti: A Game Theoretic Approach to Uncertainty

A web-service is a remote computational facility which is made available for general use by means of the internet. An orchestration is a multi-threaded computation which invokes remote services. In this paper game theory is used to analyse the behaviour of orchestration evaluations when underlying web-services are unreliable. Uncertainty profiles are proposed as a means of defining bounds on the number of service failures that can be expected during an orchestration evaluation. An uncertainty profile describes a strategic situation that can be analyzed using a zero-sum angel-daemon game with two competing players: an angel a whose objective is to minimize damage to an orchestration and a daemon d who acts in a destructive fashion. An uncertainty profile is assessed using the value of its angel daemon game. It is shown that uncertainty profiles form a partial order which is monotonic with respect to assessment.

Agreement between clinical and ultrasound biomicroscopy findings in different types of glaucoma

Purpose. To evaluate agreement between clinical examination (slit lamp examination and gonioscopy) and ultrasound biomicroscopy (UBM) in characterizing various features of the anterior chamber angle and adjacent structures. Methods. Twenty-eight patients (51 eyes) with open angle glaucoma (14), closed angle glaucoma (4), narrow angle and/or plateau iris (10), who had undergone UBM between March 94 and September 95 were studied. Evaluated parameters included angle width, iris configuration and presence of angle closure. The UBMs were reviewed in a masked fashion. Results. In 87.8% of cases there was agreement (within 10 degrees) between gonioscopic and UBM estimates of angle width. In all cases with greater than 10 degrees difference (12.2%) the angle size estimated by UBM was less than that estimated clinically. Iris configuration was graded identically in 51% of cases; the majority of disagreements (76.1%) occurred in cases graded as "regular" by gonioscopy and as "steep" by UBM. Angle closure was judged to be present more frequently by UBM. Conclusions. UBM and gonioscopy do not necessarily yield identical values for angle width, iris configuration, and presence of angle closure.

An Examination of Transformation Techniques to Investigate and Interpret Multivariate Geochemical Data Analysis: Tellus Case Study

This research aims to use the multivariate geochemical dataset, generated by the Tellus project, to investigate the appropriate use of transformation methods to maintain the integrity of geochemical data and inherent constrained behaviour in multivariate relationships. The widely used normal score transform is compared with the use of a stepwise conditional transform technique. The Tellus Project, managed by GSNI and funded by the Department of Enterprise Trade and Development and the EU’s Building Sustainable Prosperity Fund, involves the most comprehensive geological mapping project ever undertaken in Northern Ireland. Previous study has demonstrated spatial variability in the Tellus data but geostatistical analysis and interpretation of the datasets requires use of an appropriate methodology that reproduces the inherently complex multivariate relations. Previous investigation of the Tellus geochemical data has included use of Gaussian-based techniques. However, earth science variables are rarely Gaussian, hence transformation of data is integral to the approach. The multivariate geochemical dataset generated by the Tellus project provides an opportunity to investigate the appropriate use of transformation methods, as required for Gaussian-based geostatistical analysis. In particular, the stepwise conditional transform is investigated and developed for the geochemical datasets obtained as part of the Tellus project. The transform is applied to four variables in a bivariate nested fashion due to the limited availability of data. Simulation of these transformed variables is then carried out, along with a corresponding back transformation to original units. Results show that the stepwise transform is successful in reproducing both univariate statistics and the complex bivariate relations exhibited by the data. Greater fidelity to multivariate relationships will improve uncertainty models, which are required for consequent geological, environmental and economic inferences.

Clothing and Colonialism: The Dungiven costume and the fashioning of early modern identities

The entanglement of identity and personal attire in colonial settings is explored through consideration of a tattered set of clothes from late sixteenth-early seventeenth-century Ireland incorporating elements of Irish, English, and Scots fashion. Reconsideration of the clothing, recovered from a bog, provides a rare opportunity to explore the physical manifestations of processes of hybridity and mimesis, as well as the pragmatic accommodations of impoverishment and displacement in colonial settings. In addition to considering the role of material culture in colonial identity formation and negotiation, examination of what has become known as the Dungiven costume also speaks to the ongoing legacy of early modern colonial encounters, as the cultural associations of the garments, and by extension their past wearer(s), continue to be subjected to the politically charged nature of identity politics in contemporary Northern Ireland.

Mafic Plinian volcanism and ignimbrite emplacement at Tofua volcano, Tonga

Tofua Island is the largest emergent mafic volcano within the Tofua arc, Tonga, southwest Pacific. The volcano is dominated by a distinctive caldera averaging 4 km in diameter, containing a freshwater lake in the south and east. The latest paroxysmal (VEI 5-6) explosive volcanism includes two phases of activity, each emplacing a high-grade ignimbrite. The products are basaltic andesites with between 52 wt.% and 57 wt.% SiO(2). The first and largest eruption caused the inward collapse of a stratovolcano and produced the 'Tofua' ignimbrite and a sub-circular caldera located slightly northwest of the island's centre. This ignimbrite was deposited in a radial fashion over the entire island, with associated Plinian fall deposits up to 0.5 m thick on islands > 40 km away. Common sub-rounded and frequently cauliform scoria bombs throughout the ignimbrite attest to a small degree of marginal magma-water interaction. The common intense welding of the coarse-grained eruptive products, however, suggests that the majority of the erupted magma was hot, water-undersaturated and supplied at high rates with moderately low fragmentation efficiency and low levels of interaction with external water. We propose that the development of a water-saturated dacite body at shallow (<6 km) depth resulted in failure of the chamber roof to cause sudden evacuation of material, producing a Plinian eruption column. Following a brief period of quiescence, largescale faulting in the southeast of the island produced a second explosive phase believed to result from recharge of a chemically distinct magma depleted in incompatible elements. This similar, but smaller eruption, emplaced the 'Hokula' Ignimbrite sheet in the northeast of the island. A maximum total volume of 8 km(3) of juvenile material was erupted by these events. The main eruption column is estimated to have reached a height of similar to 12 km, and to have produced a major atmospheric injection of gas, and tephra recorded in the widespread series of fall deposits found on coral islands 40-80 km to the east (in the direction of regional upper-tropospheric winds). Radiocarbon dating of charcoal below the Tofua ignimbrite and organic material below the related fall units imply this eruption sequence occurred post 1,000 years BP. We estimate an eruption magnitude of 2.24x10(13) kg, sulphur release of 12 Tg and tentatively assign this eruption to the AD 1030 volcanic sulphate spike recorded in Antarctic ice sheet records.

A unified view on the effect of fibers and loading on sfrc creep through linear projection to latent structures

Creep of Steel Fiber Reinforced Concrete (SFRC) under flexural loads in the cracked state and to what extent different factors determine creep behaviour are quite understudied topics within the general field of SFRC mechanical properties. A series of prismatic specimens have been produced and subjected to sustained flexural loads. The effect of a number of variables (fiber length and slenderness, fiber content, and concrete compressive strength) has been studied in a comprehensive fashion. Twelve response variables (creep parameters measured at different times) have been retained as descriptive of flexural creep behaviour. Multivariate techniques have been used: the experimental results have been projected to their latent structure by means of Principal Components Analysis (PCA), so that all the information has been reduced to a set of three latent variables. They have been related to the variables considered and statistical significance of their effects on creep behaviour has been assessed. The result is a unified view on the effects of the different variables considered upon creep behaviour: fiber content and fiber slenderness have been detected to clearly modify the effect that load ratio has on flexural creep behaviour.

IMAGING OF SURFACE-PLASMON LAUNCH AND PROPAGATION USING A PHOTON SCANNING TUNNELING MICROSCOPE

The spectroscopic capability of the photon scanning tunneling microscope is exploited to study directly the launch and propagation of surface plasmons on thin silver films. Two input beams, of different wavelength, are incident through the prism in a prism-Ag film-air-fibre tip system. Both excite surface plasmons at the Ag-air interface and light of both wavelengths is coupled into the fibre probe via the respective surface plasmon evanescent fields. One laser beam is used for instrument control. The second, or probe beam is tightly focused on the sample, within the area of the unfocused or control beam, giving a well-defined and symmetrical, confined surface plasmon launch site. However, the image at the probe wavelength is highly asymmetrical in section with an exponential tail extending beyond one side of the launch site. This demonstrates in a very direct fashion;the propagation of surface plasmons; a propagation length of similar to 11.7 mu m is measured at a probe wavelength of 543.5 nm. On rough Ag films the excitation of localised scattering centres is also observed in addition to the launch of delocalised surface plasmons.

Operation X: Soviet Russia and the Spanish Civil War

This article offers a critical reassessment of the Soviet role in the Spanish Civil War, based on recent scholarship and declassified official documents. The author interrogates the broad historiographical consensus that reduces Soviet intervention in Spain to a sinister and nefarious force. Stalin's ignominious reputation vis-à-vis the Loyalist side is present in nearly all Western scholarship on the war, whether specialized studies by Nationalist sympathizers or Republicans in exile, or general treatments of European history written in England or America. It would be difficult to locate even a brief overview of the Civil War published outside of Russia that does not in some fashion demonize the Soviet dictator and the Soviet military assistance, code-named ‘Operation X’. The author argues that the basic error in the wide-ranging literature of this topic has always been to approach Stalin's position in Spain as one based on strength rather than weakness. If framed within the context of failure, Stalin's long-standing reputation as the villain of the Civil War may appear in a strikingly different light, and Soviets’ overall contribution to the Loyalist struggle therefore deserving a nuanced revision. The author also explores the multiple strands of the Soviet-Spanish relationship, which included not only military aid but also diplomatic, cultural and humanitarian facets.

The Ulster Covenant and the Pulse of Protestant Ulster

The signing of the Ulster Covenant on 28 September 1912 by almost 450,000 men and women was a powerful act of defiance on the part of Unionists in the context of what they perceived as the threat to their way of life represented by the Liberal Government's policy of Irish Home Rule. This article attempts to look beyond the well-studied leadership figures of Carson and Craig in order to fashion insights into the way Ulster Protestant society was mobilised around the Covenant and opposition to Home Rule. It draws attention to hitherto over-shadowed personalities who can be said to have exerted crucial local influence. It also contends that although pan-Protestant denominational unity provided the basis for the success of the Covenant, the Presbyterian community was particularly cohesive and purposeful in the campaign. The article further argues that the risk-taking defiance that came more easily to the Presbyterians, on account of a troubled history, largely evaporated in the new political circumstances of Northern Ireland when it became a separate devolved political entity within the UK from 1921.