Use of synthetic CaV2.2 Ca2+ channel peptides to study presynaptic function

Small, synthetic peptides based on specific regions of voltage-gated Ca2+ channels (VGCCs) have been widely used to study Ca2+ channel function and have been instrumental in confirming the contribution of specific amino acid sequences to interactions with putative binding partners. In particular, peptides based on the Ca2+ channel Alpha Interaction Domain (AID) on the intracellular region connecting domains I and II (the I-II loop) and the SYNaptic PRotein INTerction (synprint) site on the II-III loop have been widely used. Emerging evidence suggests that such peptides may themselves possess inherent functionality, a property that may be exploitable for future drug design. Here, we review our recent work using synthetic Ca2+ channel peptides based on sequences within the CaV2.2 amino terminal and I-II loop, originally identified as molecular determinates for G protein modulation, and their effects on VGCC function. These CaV2.2 peptides act as inhibitory modules to decrease Ca2+ influx with direct effects on VGCC gating, ultimately leading to a reduction of synaptic transmission. CaV2.2 peptides also attenuate G protein modulation of VGCCs. Amino acid substitutions generate CaV2.2 peptides with increased or decreased inhibitory effects suggesting that synthetic peptides can be used to further probe VGCC function and, potentially, form the basis for novel therapeutic development.

Detection of flooded urban areas in high resolution Synthetic Aperture Radar images using double scattering

Flooding is a particular hazard in urban areas worldwide due to the increased risks to life and property in these regions. Synthetic Aperture Radar (SAR) sensors are often used to image flooding because of their all-weather day-night capability, and now possess sufficient resolution to image urban flooding. The flood extents extracted from the images may be used for flood relief management and improved urban flood inundation modelling. A difficulty with using SAR for urban flood detection is that, due to its side-looking nature, substantial areas of urban ground surface may not be visible to the SAR due to radar layover and shadow caused by buildings and taller vegetation. This paper investigates whether urban flooding can be detected in layover regions (where flooding may not normally be apparent) using double scattering between the (possibly flooded) ground surface and the walls of adjacent buildings. The method estimates double scattering strengths using a SAR image in conjunction with a high resolution LiDAR (Light Detection and Ranging) height map of the urban area. A SAR simulator is applied to the LiDAR data to generate maps of layover and shadow, and estimate the positions of double scattering curves in the SAR image. Observations of double scattering strengths were compared to the predictions from an electromagnetic scattering model, for both the case of a single image containing flooding, and a change detection case in which the flooded image was compared to an un-flooded image of the same area acquired with the same radar parameters. The method proved successful in detecting double scattering due to flooding in the single-image case, for which flooded double scattering curves were detected with 100% classification accuracy (albeit using a small sample set) and un-flooded curves with 91% classification accuracy. The same measures of success were achieved using change detection between flooded and un-flooded images. Depending on the particular flooding situation, the method could lead to improved detection of flooding in urban areas.

Diversity between and within varieties of capitalism: transnational survey evidence

One of the central debates in contemporary socio-economics concerns the relationship between institutions and firm-level practices and the persistence of a number of alternative viable models for economic development. We examine diversity within and between specific types of capitalism using data from a transnational survey incorporating 14 organizational level practices in a sample of six capitalist archetypes, constituting 27 countries and some 6503 firms. We focus on one of the key-defining features of different varieties of capitalism, the interdependence of employers and employees. We find that there are clustering tendencies, consistent with the literature, but also considerable diversity within as well as between the varieties, although we did not find “diffuse diversity” or homogeneity. The analysis supports a complex and nuanced relationship within and between varieties of capitalism that has not been previously captured in the literature.

Acrylamide in potato crisps prepared from 20 UK-grown varieties: effects of variety and tuber storage time

Twenty varieties of field-grown potato were stored for 2 months and 6 months at 8 °C. Mean acrylamide contents in crisps prepared from all varieties at both storage times ranged from 131 μg per kg in Verdi to 5360 μg per kg in Pentland Dell. In contrast to previous studies, the longer storage period did not affect acrylamide formation significantly for most varieties, the exceptions being Innovator, where acrylamide formation increased, and Saturna, where it decreased. Four of the five varieties designated as suitable for crisping produced crisps with acrylamide levels below the European Commission indicative value of 1000 μg per kg (Saturna, Lady Rosetta, Lady Claire, and Verdi); the exception was Hermes. Two varieties more often used for French fries, Markies and Fontane, also produced crisps with less than 1000 μg per kg acrylamide. Correlations between acrylamide, its precursors and crisp colour are described, and the implications of the results for production of potato crisps are discussed.

Structural stability of the synthetic thermoelectric ternary and nickel-substituted tetrahedrite phases

The purity and structural stability of the high thermoelectric performance Cu12Sb4S13 and Cu10.4Ni1.6Sb4S13 tetrahedrite phases, synthesized by solid–liquid–vapor reaction and Spark Plasma Sintering, were studied at high temperature by Rietveld refinement using high resolution X-ray powder diffraction data, DSC/TG measurements and high resolution transmission electron microscopy. In a complementary study, the crystal structure of Cu10.5Ni1.5Sb4S13 as a function of temperature was investigated by powder neutron diffraction. The temperature dependence of the structural stability of ternary Cu12Sb4S13 is markedly different to that of the nickel-substituted phases, providing clear evidence for the significant and beneficial role of nickel substitution on both sample purity and stability of the tetrahedrite phase. Moreover, kinetic effects on the phase stability/decomposition have been identified and discussed in order to determine the maximum operating temperature for thermoelectric applications. The thermoelectric properties of these compounds have been determined for high density samples (>98%) prepared by Spark Plasma Sintering and therefore can be used as reference values for tetrahedrite samples. The maximum ZT of 0.8 was found for Cu10.4Ni1.6Sb4S13 at 700 K.

The potential of flood forecasting using a variable-resolution global Digital Terrain Model and flood extents from Synthetic Aperture Radar images

A basic data requirement of a river flood inundation model is a Digital Terrain Model (DTM) of the reach being studied. The scale at which modeling is required determines the accuracy required of the DTM. For modeling floods in urban areas, a high resolution DTM such as that produced by airborne LiDAR (Light Detection And Ranging) is most useful, and large parts of many developed countries have now been mapped using LiDAR. In remoter areas, it is possible to model flooding on a larger scale using a lower resolution DTM, and in the near future the DTM of choice is likely to be that derived from the TanDEM-X Digital Elevation Model (DEM). A variable-resolution global DTM obtained by combining existing high and low resolution data sets would be useful for modeling flood water dynamics globally, at high resolution wherever possible and at lower resolution over larger rivers in remote areas. A further important data resource used in flood modeling is the flood extent, commonly derived from Synthetic Aperture Radar (SAR) images. Flood extents become more useful if they are intersected with the DTM, when water level observations (WLOs) at the flood boundary can be estimated at various points along the river reach. To illustrate the utility of such a global DTM, two examples of recent research involving WLOs at opposite ends of the spatial scale are discussed. The first requires high resolution spatial data, and involves the assimilation of WLOs from a real sequence of high resolution SAR images into a flood model to update the model state with observations over time, and to estimate river discharge and model parameters, including river bathymetry and friction. The results indicate the feasibility of such an Earth Observation-based flood forecasting system. The second example is at a larger scale, and uses SAR-derived WLOs to improve the lower-resolution TanDEM-X DEM in the area covered by the flood extents. The resulting reduction in random height error is significant.

Varieties of semantic ‘access’ deficit in Wernicke’s aphasia and semantic aphasia

Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia (SA), characterised by poor executive control of semantic processing across verbal and nonverbal modalities, and (ii) Wernicke’s aphasia (WA), associated with poor auditory-verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well-understood. Both patient groups exhibit some type of semantic ‘access’ deficit, as opposed to the ‘storage’ deficits observed in semantic dementia. Nevertheless, existing descriptions suggest these patients might have different varieties of ‘access’ impairment – related to difficulty resolving competition (in SA) vs. initial activation of concepts from sensory inputs (in WA). We used a case-series design to compare WA and SA patients on Warrington’s paradigmatic assessment of semantic ‘access’ deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic ‘blocking’ effects). WA and SA patients were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability – one that mapped onto classical ‘syndromes’ and one that did not – predicted aspects of the semantic ‘access’ deficit. Both SA and WA cases showed multimodal semantic impairment, although as expected the WA group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially beneficial effects of stimulus repetition: WA cases showed initial improvement with repetition of words and pictures, while in SA, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the harmful effects of repetition: the ability to re-select both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, SA and WA patients have partially distinct impairment of semantic ‘access’ but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks.

Varieties of parliamentarianism

From the start of the English civil war, the parliamentarians were a fragmented coalition, held together by distrust of the king and a belief that Parliament was entitled to lead action to remedy his government’s deficiencies. The driving motivations of parliamentarians were various, including the religious commitments of puritanism, legalistic thought about the ancient constitution, and more radical notions of republicanism or natural rights. Historians have disputed whether parliamentarianism had an inherent strand of radicalism – or radical potential – from the early 1640s, but radicalization certainly took place as the civil wars went on, alongside more ‘conservative’ reactions against the propaganda and wartime measures employed by parliament. Parliamentarian radicalism itself was varied in character, embracing the Levellers’ populism, parliamentary absolutism, and millenarian and providentialist ideas.

Improving the TanDEM-X Digital Elevation Model for flood modelling using flood extents from Synthetic Aperture Radar images

The topography of many floodplains in the developed world has now been surveyed with high resolution sensors such as airborne LiDAR (Light Detection and Ranging), giving accurate Digital Elevation Models (DEMs) that facilitate accurate flood inundation modelling. This is not always the case for remote rivers in developing countries. However, the accuracy of DEMs produced for modelling studies on such rivers should be enhanced in the near future by the high resolution TanDEM-X WorldDEM. In a parallel development, increasing use is now being made of flood extents derived from high resolution Synthetic Aperture Radar (SAR) images for calibrating, validating and assimilating observations into flood inundation models in order to improve these. This paper discusses an additional use of SAR flood extents, namely to improve the accuracy of the TanDEM-X DEM in the floodplain covered by the flood extents, thereby permanently improving this DEM for future flood modelling and other studies. The method is based on the fact that for larger rivers the water elevation generally changes only slowly along a reach, so that the boundary of the flood extent (the waterline) can be regarded locally as a quasi-contour. As a result, heights of adjacent pixels along a small section of waterline can be regarded as samples with a common population mean. The height of the central pixel in the section can be replaced with the average of these heights, leading to a more accurate estimate. While this will result in a reduction in the height errors along a waterline, the waterline is a linear feature in a two-dimensional space. However, improvements to the DEM heights between adjacent pairs of waterlines can also be made, because DEM heights enclosed by the higher waterline of a pair must be at least no higher than the corrected heights along the higher waterline, whereas DEM heights not enclosed by the lower waterline must in general be no lower than the corrected heights along the lower waterline. In addition, DEM heights between the higher and lower waterlines can also be assigned smaller errors because of the reduced errors on the corrected waterline heights. The method was tested on a section of the TanDEM-X Intermediate DEM (IDEM) covering an 11km reach of the Warwickshire Avon, England. Flood extents from four COSMO-SKyMed images were available at various stages of a flood in November 2012, and a LiDAR DEM was available for validation. In the area covered by the flood extents, the original IDEM heights had a mean difference from the corresponding LiDAR heights of 0.5 m with a standard deviation of 2.0 m, while the corrected heights had a mean difference of 0.3 m with standard deviation 1.2 m. These figures show that significant reductions in IDEM height bias and error can be made using the method, with the corrected error being only 60% of the original. Even if only a single SAR image obtained near the peak of the flood was used, the corrected error was only 66% of the original. The method should also be capable of improving the final TanDEM-X DEM and other DEMs, and may also be of use with data from the SWOT (Surface Water and Ocean Topography) satellite.

The Cold War and its aftermath in the Americas: the search for a synthetic interpretation of U.S. policy

More than two decades have passed since the fall of the Berlin Wall and the transfer of the Cold War file from a daily preoccupation of policy makers to a more detached assessment by historians. Scholars of U.S.-Latin American relations are beginning to take advantage both of the distance in time and of newly opened archives to reflect on the four decades that, from the 1940s to the 1980s, divided the Americas, as they did much of the world. Others are seeking to understand U.S. policy and inter-American relations in the post-Cold War era, a period that not only lacks a clear definition but also still has no name. Still others have turned their gaze forward to offer policies in regard to the region for the new Obama administration. Numerous books and review essays have addressed these three subjects—the Cold War, the post-Cold War era, and current and future issues on the inter-American agenda. Few of these studies attempt, however, to connect the three subjects or to offer new and comprehensive theories to explain the course of U.S. policies from the beginning of the twentieth century until the present. Indeed, some works and policy makers continue to use the mind-sets of the Cold War as though that conflict were still being fought. With the benefit of newly opened archives, some scholars have nevertheless drawn insights from the depths of the Cold War that improve our understanding of U.S. policies and inter-American relations, but they do not address the question as to whether the United States has escaped the longer cycle of intervention followed by neglect that has characterized its relations with Latin America. Another question is whether U.S. policies differ markedly before, during, and after the Cold War. In what follows, we ask whether the books reviewed here provide any insights in this regard and whether they offer a compass for the future of inter-American relations. We also offer our own thoughts as to how their various perspectives could be synthesized to address these questions more comprehensively.