Direct observation of charge inversion by multivalent ions as a universal electrostatic phenomenon

We have directly observed reversal of the polarity of charged surfaces in water upon the addition of tri- and quadrivalent ions using atomic force microscopy. The bulk concentration of multivalent ions at which charge inversion reversibly occurs depends only very weakly on the chemical composition, surface structure, size and lipophilicity of the ions, but is dominated by their valence. These results support the theoretical proposal that spatial correlations between ions are the driving mechanism behind charge inversion.Comment: submitted to PRL, 26-04-2004 Changed the presentation of the theory at the end of the paper. Changed small error in estimate of prefactor ("w" in first version) of equation

Modelling the spatial distribution of DEM Error

Assessment of a DEM’s quality is usually undertaken by deriving a measure of DEM accuracy – how close the DEM’s elevation values are to the true elevation. Measures such as Root Mean Squared Error and standard deviation of the error are frequently used. These measures summarise elevation errors in a DEM as a single value. A more detailed description of DEM accuracy would allow better understanding of DEM quality and the consequent uncertainty associated with using DEMs in analytical applications. The research presented addresses the limitations of using a single root mean squared error (RMSE) value to represent the uncertainty associated with a DEM by developing a new technique for creating a spatially distributed model of DEM quality – an accuracy surface. The technique is based on the hypothesis that the distribution and scale of elevation error within a DEM are at least partly related to morphometric characteristics of the terrain. The technique involves generating a set of terrain parameters to characterise terrain morphometry and developing regression models to define the relationship between DEM error and morphometric character. The regression models form the basis for creating standard deviation surfaces to represent DEM accuracy. The hypothesis is shown to be true and reliable accuracy surfaces are successfully created. These accuracy surfaces provide more detailed information about DEM accuracy than a single global estimate of RMSE

Promiscuous Binding of Invariant Chain-Derived CLIP Peptide to Distinct HLA-I Molecules Revealed in Leukemic Cells

Antigen presentation by HLA class I (HLA-I) and HLA class II (HLA-II) complexes is achieved by proteins that are specific for their respective processing pathway. The invariant chain (Ii)-derived peptide CLIP is required for HLA-II-mediated antigen presentation by stabilizing HLA-II molecules before antigen loading through transient and promiscuous binding to different HLA-II peptide grooves. Here, we demonstrate alternative binding of CLIP to surface HLA-I molecules on leukemic cells. In HLA-II-negative AML cells, we found plasma membrane display of the CLIP peptide. Silencing Ii in AML cells resulted in reduced HLA-I cell surface display, which indicated a direct role of CLIP in the HLA-I antigen presentation pathway. In HLA-I-specific peptide eluates from B-LCLs, five Ii-derived peptides were identified, of which two were from the CLIP region. In vitro peptide binding assays strikingly revealed that the eluted CLIP peptide RMATPLLMQALPM efficiently bound to four distinct HLA-I supertypes (-A2, -B7, -A3, -B40). Furthermore, shorter length variants of this CLIP peptide also bound to these four supertypes, although in silico algorithms only predicted binding to HLA-A2 or -B7. Immunization of HLA-A2 transgenic mice with these peptides did not induce CTL responses. Together these data show a remarkable promiscuity of CLIP for binding to a wide variety of HLA-I molecules. The found participation of CLIP in the HLA-I antigen presentation pathway could reflect an aberrant mechanism in leukemic cells, but might also lead to elucidation of novel processing pathways or immune escape mechanisms

Alternative Ii-independent antigen-processing pathway in leukemic blasts involves TAP-dependent peptide loading of HLA class II complexes

During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed MIICs. This study explores an alternative HLA class II presentation pathway in leukemic blasts that involves proteasome and transporter associated with antigen processing (TAP)-dependent peptide loading. Although HLA-DR did associate with Ii, Ii silencing in the human class II-associated invariant chain peptide (CLIP)-negative KG-1 myeloid leukemic cell line did not affect total and plasma membrane expression levels of HLA-DR, as determined by western blotting and flow cytometry. Since HLA-DR expression does require peptide binding, we examined the role of endogenous antigen-processing machinery in HLA-DR presentation by CLIP− leukemic blasts. The suppression of proteasome and TAP function using various inhibitors resulted in decreased HLA-DR levels in both CLIP− KG-1 and ME-1 blasts. Simultaneous inhibition of TAP and Ii completely down-modulated the expression of HLA-DR, demonstrating that together these molecules form the key mediators of HLA class II antigen presentation in leukemic blasts. By the use of a proteasome- and TAP-dependent pathway for HLA class II antigen presentation, CLIP− leukemic blasts might be able to present a broad range of endogenous leukemia-associated peptides via HLA class II to activate leukemia-specific CD4+ T cells

Beyond ‘just’ flood risk management: the potential for—and limits to—alleviating flood disadvantage

The threat of flooding poses a considerable challenge for justice. Not only are more citizens becoming exposed to risk, but they are expected to play increasingly active roles in flood risk management. However, until recently, few efforts have charted broader understandings of disadvantage relating to flood risk exposure. Drawing upon social science scholarship that has long been sensitive to concerns related to justice, we deploy and develop the notion of flood disadvantage as a means to assess the challenges to more ‘just’ flood risk management. We contend that the concept of flood disadvantage offers a useful lens to appreciate the constraints of technical approaches to flood risk management, in particular, its limited ability to incorporate complex social elements such as how individuals have differing vulnerabilities and sensitivities to flooding and uneven abilities to engage with risk agendas. The notion highlights the compounding interactions between flooding and other social disadvantages across multiple public policy areas and scales. We argue a fuller acknowledgement of the socio-spatial-temporal dimensions of intersecting disadvantages can help sensitise technical risk analyses that tend to see people and communities as homogeneous entities in a given spatiality. In doing so we can better reveal why some individuals or communities are more vulnerable to disasters or are slower to recover than others. Finally, we outline the challenges in turning more ‘just’ flood risk management from an abstract notion into one that could inform future practice

A review of modelling methodologies for flood source area (FSA) identification

Flooding is an important global hazard that causes an average annual loss of over 40 billion USD and affects a population of over 250 million globally. The complex process of flooding depends on spatial and temporal factors such as weather patterns, topography, and geomorphology. In urban environments where the landscape is ever-changing, spatial factors such as ground cover, green spaces, and drainage systems have a significant impact. Understanding source areas that have a major impact on flooding is, therefore, crucial for strategic flood risk management (FRM). Although flood source area (FSA) identification is not a new concept, its application is only recently being applied in flood modelling research. Continuous improvements in the technology and methodology related to flood models have enabled this research to move beyond traditional methods, such that, in recent years, modelling projects have looked beyond affected areas and recognised the need to address flooding at its source, to study its influence on overall flood risk. These modelling approaches are emerging in the field of FRM and propose innovative methodologies for flood risk mitigation and design implementation; however, they are relatively under-examined. In this paper, we present a review of the modelling approaches currently used to identify FSAs, i.e. unit flood response (UFR) and adaptation-driven approaches (ADA). We highlight their potential for use in adaptive decision making and outline the key challenges for the adoption of such approaches in FRM practises

A Microfabricated 4-Electrode Conductivity Sensor with Enhanced Range

Conductivity is a routinely measured parameter to assess impurities in water. Changing the geometry from parallel plate electrodes to planar microfabricated dual-band or interdigitated electrodes, these sensors could be miniaturized. Based on this approach, we designed 2-electrode conductivity sensors and compared their performance with a commercially available device. Adding another electrode pair (either as dual-band or meandering between interdigitated electrodes), a 4-electrode sensor was formed for which the measuring range could be enhanced to 3 × 10−6⁻12 × 10−3 S/cm