MAP kinase pathway signalling is essential for extracellular matrix determined mammary epithelial cell survival

Mammary epithelial cells in primary cell culture require both growth factors and specific extracellular matrix (ECM)-attachment for survival. Here we demonstrate for the first time that inhibition of the ECM-induced Erk 1/Erk 2 (p42/44 MAPK) pathway, by PD 98059, leads to apoptosis in these cells. Associated with this cell death is a possible compensatory signalling through the p38 MAP kinase pathway the inhibition of which, by SB 203580, leads to a more rapid onset of apoptosis. This provides evidence for a hitherto undescribed Erk 1/Erk 2 to p38 MAP kinase pathway 'cross-talk' that is essential for the survival of these cells. The cell death associated with inhibition of these two MAP kinase pathways however, occurred in the presence of insulin that activates the classical PI-3 kinase-dependent Akt/PKB survival signals and Akt phosphorylation. Cell death induced by inhibition of the MAP kinase pathways did not affect Akt phosphorylation and may, thus, be independent of PI-3 kinase signalling.

Defending the Irish Border: The Map of Watchful Architecture

This chapter offers an analysis of a map of the Irish border. The Map of Watchful Architecture charts the history of defensive structures in the border region.

Demonstrating the Transferability and the Descriptive Power of Sketch-Map

Increasingly, it is recognized that new automated forms of analysis are required to understand the high-dimensional output obtained from atomistic simulations. Recently, we introduced a new dimensionality reduction algorithm, sketch-map, that was designed specifically to work with data from molecular dynamics trajectories. In what follows, we provide more details on how this algorithm works and on how to set its parameters. We also test it on two well-studied Lennard-Jones clusters and show that the coordinates we extract using this algorithm are extremely robust. In particular, we demonstrate that the coordinates constructed for one particular Lennard-Jones cluster can be used to describe the configurations adopted by a second, different cluster and even to tell apart different phases of bulk Lennard-Jonesium.

Using sketch-map coordinates to analyze and bias molecular dynamics simulations

When examining complex problems, such as the folding of proteins, coarse grained descriptions of the system drive our investigation and help us to rationalize the results. Oftentimes collective variables (CVs), derived through some chemical intuition about the process of interest, serve this purpose. Because finding these CVs is the most difficult part of any investigation, we recently developed a dimensionality reduction algorithm, sketch-map, that can be used to build a low-dimensional map of a phase space of high-dimensionality. In this paper we discuss how these machine-generated CVs can be used to accelerate the exploration of phase space and to reconstruct free-energy landscapes. To do so, we develop a formalism in which high-dimensional configurations are no longer represented by low-dimensional position vectors. Instead, for each configuration we calculate a probability distribution, which has a domain that encompasses the entirety of the low-dimensional space. To construct a biasing potential, we exploit an analogy with metadynamics and use the trajectory to adaptively construct a repulsive, history-dependent bias from the distributions that correspond to the previously visited configurations. This potential forces the system to explore more of phase space by making it desirable to adopt configurations whose distributions do not overlap with the bias. We apply this algorithm to a small model protein and succeed in reproducing the free-energy surface that we obtain from a parallel tempering calculation.

Simplifying the representation of complex free-energy landscapes using sketch-map

A new scheme, sketch-map, for obtaining a low-dimensional representation of the region of phase space explored during an enhanced dynamics simulation is proposed. We show evidence, from an examination of the distribution of pairwise distances between frames, that some features of the free-energy surface are inherently high-dimensional. This makes dimensionality reduction problematic because the data does not satisfy the assumptions made in conventional manifold learning algorithms We therefore propose that when dimensionality reduction is performed on trajectory data one should think of the resultant embedding as a quickly sketched set of directions rather than a road map. In other words, the embedding tells one about the connectivity between states but does not provide the vectors that correspond to the slow degrees of freedom. This realization informs the development of sketch-map, which endeavors to reproduce the proximity information from the high-dimensionality description in a space of lower dimensionality even when a faithful embedding is not possible.

Quantification of interpoint topographic correlations of threshold values in glaucomatous visual fields

Purpose: The authors sought to quantify neighboring and distant interpoint correlations of threshold values within the visual field in patients with glaucoma. Methods: Visual fields of patients with confirmed or suspected glaucoma were analyzed (n = 255). One eye per patient was included. Patients were examined using the 32 program of the Octopus 1-2-3. Linear regression analysis among each of the locations and the rest of the points of the visual field was performed, and the correlation coefficient was calculated. The degree of correlation was categorized as high (r > 0.66), moderate (0.66 = r > 0.33), or low (r = 0.33). The standard error of threshold estimation was calculated. Results: Most locations of the visual field had high and moderate correlations with neighboring points and with distant locations corresponding to the same nerve fiber bundle. Locations of the visual field had low correlations with those of the opposite hemifield, with the exception of locations temporal to the blind spot. The standard error of threshold estimation increased from 0.6 to 0.9 dB with an r reduction of 0.1. Conclusion: Locations of the visual field have highest interpoint correlation with neighboring points and with distant points in areas corresponding to the distribution of the retinal nerve fiber layer. The quantification of interpoint correlations may be useful in the design and interpretation of visual field tests in patients with glaucoma.

Reproducibility of optic disk topographic measurements with the Topcon ImageNet and the Heidelberg Retina Tomograph

Objective: To compare the reproducibility of optic disk measurements provided by an image analyzer and a scanning laser tomograph. Methods: Ten images of the same eye of 10 normal volunteers were taken with the Heidelberg Retina Tomograph and with the Topcon ImageNet. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were used to evaluate the reproducibility of the measurements. Results: Eleven parameters were analyzed with the Topcon ImageNet. Six parameters (55%) had ICC greater than 90%. Four parameters (36%) had CV less than 10%. Twelve parameters were evaluated with the Heidelberg Retina Tomograph. Nine parameters (75%) had ICC over 90%. Nine parameters (75%) had CV less than 10%. Conclusion: Both systems provided reproducible data. The optic disk parameters provided by the Heidelberg Retina Tomograph had a better reproducibility than those obtained from the Topcon ImageNet.

Invariant Information Local Sub-map Filter (IILSF) for Efficient Simultaneous Localisation and Mapping of Large Environments

This paper presents an Invariant Information Local Sub-map Filter (IILSF) as a technique for consistent Simultaneous Localisation and Mapping (SLAM) in a large environment. It harnesses the benefits of sub-map technique to improve the consistency and efficiency of Extended Kalman Filter (EKF) based SLAM. The IILSF makes use of invariant information obtained from estimated locations of features in independent sub-maps, instead of incorporating every observation directly into the global map. Then the global map is updated at regular intervals. Applying this technique to the EKF based SLAM algorithm: (a) reduces the computational complexity of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. Simulation results show that the method was able to accurately fuse local map observations to generate an efficient and consistent global map, in addition to significantly reducing computational cost and data association ambiguities.

The Map Defines the Territory: Remodelling NGO Partnerships for Knowledge Translation in Transition Contexts

The initial impetus for a theoretical exploration of organisational relationships is based on case study research on a Bulgarian NGO's implementation of values and goals into practices under a guiding relationship from a very experienced UK organisation in the same field. Findings diverged from conventional accounts of developing NGOs' dependence on more developed counterparts and that case study findings characterised the inter- dependency between the two organisations as more alike to a collaborative knowledge ...

The Map of Watchful Architecture

The international border between Northern Ireland and the South (the Republic of Ireland) came into being in 1922, but there are many important historical antecedents to the notion and expression of spatial separation in this borderland. The author identifies historical precedents and links them to recent defensive features in order to generate a 'map of watchful architecture' that includes recent and much older elements.

Fictional Ulster:A map of places created by writers

Ballybeg, the fictitious setting for Brian Friel’s plays, is more famous than most real villages in Ulster. Despite not existing, the village has a kind of cultural and geographic life. This is part of what this map is about. It locates and charts Ulster’s fictional places — places invented by writers down through the years. These places have meaning too, they are part of how Ulster pictures itself and how others picture Ulster.

The Map of Connections 3.1: Unofficial and previously unmapped Irish border crossings

I charted unofficial border-crossings along Ireland's border, those not found on any other map.

During many surveys of Ireland's border I discovered that it is often perforated. Gates are set in hedgerows for the convenience of farmers, stepping stones and community-built bridges span rivers, walkers’ routes and muddy by-ways go wherever they please. These kinds of connections have always been there, although I think it is fair to say that their numbers have increased during the Peace Process. Roads blocked or cratered during the Troubles are being re-connected at a rate too fast for the Ordnance Survey to keep up with. On the local level cross-border movement is quietly happening, unchecked and often unmapped, until now.

This map attempts to throw the borderline in perpendicular, showing it as a place of connection rather than division.

The Map of Watchful Architecture 2.0:Defensive forms along Ireland's border

For The Map of Watchful Architecture I only concerned myself with defensive architecture along the Border. As the map followed a border it came out as a wavy line of points. This was largely artificial, I only charted architecture within the Border corridor, but was not entirely artificial. That linear landscape has long been staked-out by the regularity of certain kinds of architecture. The 1st/2nd century Black Pig’s Dyke and Dorsey correspond with today’s Border. The concentration of souterrains in north Louth indicate that it may have been a volatile interface zone in later centuries. In 1618 Londonderry and its walls were built. Further north and two centuries later, Martello Towers were constructed to watch over Lough Foyle. During the Second World War pillboxes and observation posts were manned along the Border, close to what was now an international frontier. Then came the Operation Banner installations built during The Troubles. All this adds up to be one of the longest unbroken traditions of defensive architecture anywhere in Western Europe, a tradition some thought finally broken as the last of the Operation Banner towers were de-installed in 2007. But, take a bus south across the Border and you will often be pulled over by the Garda Síochána. They ID check the passengers in an attempt to stop illegal immigration via the UK. What about illegal immigrants who walk through the fields or along quiet lanes? They will have understood the Border is not really how it seems on most maps. It is not a solid line, it is a row of points.

A review of topographic controls on moraine distribution

Ice-marginal moraines are often used to reconstruct the dimensions of former ice masses, which are then used as proxies for palaeoclimate. This approach relies on the assumption that the distribution of moraines in the modern landscape is an accurate reflection of former ice margin positions during climatically controlled periods of ice margin stability. However, the validity of this assumption is open to question, as a number of additional, nonclimatic factors are known to influence moraine distribution. This review considers the role played by topography in this process, with specific focus on moraine formation, preservation, and ease of identification (topoclimatic controls are not considered). Published literature indicates that the importance of topography in regulating moraine distribution varies spatially, temporally, and as a function of the ice mass type responsible for moraine deposition. In particular, in the case of ice sheets and ice caps ( > 1000 km2), one potentially important topographic control on where in a landscape moraines are deposited is erosional feedback, whereby subglacial erosion causes ice masses to become less extensive over successive glacial cycles. For the marine-terminating outlets of such ice masses, fjord geometry also exerts a strong control on where moraines are deposited, promoting their deposition in proximity to valley narrowings, bends, bifurcations, where basins are shallow, and/or in the vicinity of topographic bumps. Moraines formed at the margins of ice sheets and ice caps are likely to be large and readily identifiable in the modern landscape. In the case of icefields and valley glaciers (10–1000 km2), erosional feedback may well play some role in regulating where moraines are deposited, but other factors, including variations in accumulation area topography and the propensity for moraines to form at topographic pinning points, are also likely to be important. This is particularly relevant where land-terminating glaciers extend into piedmont zones (unconfined plains, adjacent to mountain ranges) where large and readily identifiable moraines can be deposited. In the case of cirque glaciers (< 10 km2), erosional feedback is less important, but factors such as topographic controls on the accumulation of redistributed snow and ice and the availability of surface debris, regulate glacier dimensions and thereby determine where moraines are deposited. In such cases, moraines are likely to be small and particularly susceptible to post-depositional modification, sometimes making them difficult to identify in the modern landscape. Based on this review, we suggest that, despite often being difficult to identify, quantify, and mitigate, topographic controls on moraine distribution should be explicitly considered when reconstructing the dimensions of palaeoglaciers and that moraines should be judiciously chosen before being used as indirect proxies for palaeoclimate (i.e., palaeoclimatic inferences should only be drawn from moraines when topographic controls on moraine distribution are considered insignificant).