Synthesis and incorporation into cyclic peptides of tolan amino acids and their hydrogenated congeners: construction of an array of A–B-loop mimetics of the Cε3 domain of human IgE

The disruption of the human immunolobulin E–high affinity receptor I (IgE–FcεRI) protein–protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A–B loop within the Cε3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 660 μM) is displayed by the peptide containing a 2,2′-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A–B loop epitope in IgE.

Smoothed histogram modification for image processing

The technique of constructing a transformation, or regrading, of a discrete data set such that the histogram of the transformed data matches a given reference histogram is commonly known as histogram modification. The technique is widely used for image enhancement and normalization. A method which has been previously derived for producing such a regrading is shown to be “best” in the sense that it minimizes the error between the cumulative histogram of the transformed data and that of the given reference function, over all single-valued, monotone, discrete transformations of the data. Techniques for smoothed regrading, which provide a means of balancing the error in matching a given reference histogram against the information lost with respect to a linear transformation are also examined. The smoothed regradings are shown to optimize certain cost functionals. Numerical algorithms for generating the smoothed regradings, which are simple and efficient to implement, are described, and practical applications to the processing of LANDSAT image data are discussed.

Intrusions in trauma and psychosis: information processing and phenomenology

Background: Intrusions are common symptoms of both posttraumatic stress disorder (PTSD) and schizophrenia. Steel et al (2005) suggest that an information processing style characterized by weak trait contextual integration renders psychotic individuals vulnerable to intrusive experiences. This ‘contextual integration hypothesis’ was tested in individuals reporting anomalous experiences in the absence of a need-for-care. Methods: Twenty-six low schizotypes and twenty-three individuals reporting anomalous experiences were shown a traumatic film with and without a concurrent visuo-spatial task. Participants rated post-traumatic intrusions for frequency and form, and completed self-report measures of information processing style. It was predicted that, due to their weaker trait contextual integration, the anomalous experiences group would (1) exhibit more intrusions following exposure to the trauma-film; (2) display intrusions characterised by more PTSD qualities and (3) show a greater reduction of intrusions with the concurrent visuo-spatial task. Results: As predicted, the anomalous experiences group reported a lower level of trait contextual integration and more intrusions than the low schizotypes, both immediately after watching the film, and during the following seven days. Their post-traumatic intrusive memories were more PTSD-like (more intrusive, vivid and associated with emotion). The visuo-spatial task had no effect on number of intrusions in either group. Conclusions: These findings provide some support for the proposal that weak trait contextual integration underlies the development of intrusions within both PTSD and psychosis.

Characterisation of Escherichia fergusonii isolates from farm animals using an Escherichia coli virulence gene array and tissue culture adherence assays

Escherichia fergusonii has been associated with a wide variety of intestinal and extra-intestinal infections in both humans and animals but, despite strong circumstantial evidence, the degree to which the organism is responsible for the pathologies identified remains uncertain. Thirty isolates of E fergusonii collected between 2003 and 2004 were screened using an Escherichia coli virulence gene array to test for the presence of homologous virulence genes in E. fergusonii. The iss (increased serum survival) gene was present in 13/30 (43%) of the test strains and the prfB (P-related fimbriae regulatory) and ireA (siderophore receptor IreA) genes were also detected jointly in 3/30 (10%) strains. No known virulence genes were detected in 14/30 (47%) of strains. Following confirmatory PCR and sequence analysis, the E. fergusonii prfB, iss and ireA genes shared a high degree of sequence similarity to their counterparts in E. coli, and a particular resemblance was noted with the E. coli strain APEC O1 pathogenicity island. In tissue culture adherence assays, nine E. fergusonii isolates associated with HEp-2 cells with a 'localised adherence' or 'diffuse adherence' phenotype, and they proved to be moderately invasive. The E fergusonii isolates in this study possess both some phenotypic and genotypic features linked to known pathotypes of E coli, and support existing evidence that strains of E fergusonii may act as an opportunistic pathogens, although their specific virulence factors may need to be explored. Crown Copyright (c) 2008 Published by Elsevier Ltd. All rights reserved.

Processing empty categories in a second language: When naturalistic exposure fills the (intermediate) gap

An ongoing debate on second language (L2) processing revolves around whether or not L2 learners process syntactic information similarly to monolinguals (L1), and what factors lead to a native-like processing. According to the Shallow Structure Hypothesis (Clahsen & Felser, 2006a), L2 learners’ processing does not include abstract syntactic features, such as intermediate gaps of wh-movement, but relies more on lexical/semantic information. Other researchers have suggested that naturalistic L2 exposure can lead to native-like processing (Dussias, 2003). This study investigates the effect of naturalistic exposure in processing wh-dependencies. Twenty-six advanced Greek learners of L2 English with an average nine years of naturalistic exposure, 30 with classroom exposure, and 30 native speakers of English completed a self-paced reading task with sentences involving intermediate gaps. L2 learners with naturalistic exposure showed evidence of native-like processing of the intermediate gaps, suggesting that linguistic immersion can lead to native-like abstract syntactic processing in the L2.

Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array

Background A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNPbased linkage map of an apple rootstock progeny. Results Of the 7,867 Malus SNP markers on the array, 1,823 (23.2 %) were heterozygous in one of the two parents of the progeny, 1,007 (12.8 %) were heterozygous in both parental genotypes, whilst just 2.8 % of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the ‘Golden Delicious’ genome sequence. A total of 311 markers (13.7 % of all mapped markers) mapped to positions that conflicted with their predicted positions on the ‘Golden Delicious’ pseudo-chromosomes, indicating the presence of paralogous genomic regions or misassignments of genome sequence contigs during the assembly and anchoring of the genome sequence. Conclusions We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the ‘Golden Delicious’ reference sequence will assist in the continued improvement of the genome sequence assembly for that variety.

Assimilation of RAPID array observations into an ocean model

Experiments assimilating the RAPID dataset of deep temperature and salinity profiles at 26.5°N on the western and eastern Atlantic boundaries into a 1° global NEMO ocean model have been performed. The meridional overturning circulation (MOC) is then assessed against the transports calculated directly from observations. The best initialization found for this short period was obtained by assimilating the EN3 upper-ocean hydrography database prior to 2004, after which different methods of assimilating 5-day average RAPID profiles at the western boundary were tested. The model MOC is strengthened by ∼ 2 Sv giving closer agreement with the RAPID array transports, when the western boundary profiles are assimilated only below 900 m (the approximate depth of the Florida Straits, which are not well resolved) and when the T,S observations are spread meridionally from 10 to 35°N along the deep western boundary. The use of boundary-focused covariances has the largest impact on the assimilation results, otherwise using more conventional Gaussian covariances has a very local impact on the MOC at 26°N with strong adverse impacts on the MOC stream function at higher and lower latitudes. Even using boundary-focused covariances only enables the MOC to be strengthened for ∼ 2 years, after which the increased transport of warm waters leads to a negative feedback on water formation in the subpolar gyre which then reduces the MOC. This negative feedback can be mitigated if EN3 hydrography data continue to be assimilated along with the RAPID array boundary data. Copyright © 2012 Royal Meteorological Society and Crown in the right of Canada.

Keeping the world at hand: rapid visuomotor processing for hand-object interactions

The existence of hand-centred visual processing has long been established in the macaque premotor cortex. These hand-centred mechanisms have been thought to play some general role in the sensory guidance of movements towards objects, or, more recently, in the sensory guidance of object avoidance movements. We suggest that these hand-centred mechanisms play a specific and prominent role in the rapid selection and control of manual actions following sudden changes in the properties of the objects relevant for hand-object interactions. We discuss recent anatomical and physiological evidence from human and non-human primates, which indicates the existence of rapid processing of visual information for hand-object interactions. This new evidence demonstrates how several stages of the hierarchical visual processing system may be bypassed, feeding the motor system with hand-related visual inputs within just 70 ms following a sudden event. This time window is early enough, and this processing rapid enough, to allow the generation and control of rapid hand-centred avoidance and acquisitive actions, for aversive and desired objects, respectively

Microsaccades distinguish between global and local visual processing

Much is known about the functional mechanisms involved in visual search. Yet, the fundamental question of whether the visual system can perform different types of visual analysis at different spatial resolutions still remains unsettled. In the visual-attention literature, the distinction between different spatial scales of visual processing corresponds to the distinction between distributed and focused attention. Some authors have argued that singleton detection can be performed in distributed attention, whereas others suggest that even such a simple visual operation involves focused attention. Here we showed that microsaccades were spatially biased during singleton discrimination but not during singleton detection. The results provide support to the hypothesis that some coarse visual analysis can be performed in a distributed attention mode.

Nuclear fuel cycles: interfaces with the environment

The waste materials generated in the nuclear fuel cycle are very varied,ranging from the tailings arising from mining and processing uranium ore, depleted uranium in a range of chemical forms, to a range of process wastes of differing activities and properties. Indeed, the wastes generated are intimately linked to the options selected in operating the nuclear fuel cycle, most obviously to the management of spent fuel. An open fuel cycle implies the disposal of highly radioactive spent fuel, whereas a closed fuel cycle generates a complex array of waste streams. On the other hand, a closed fuel cycle offers options for waste management, for example reduction in highly active waste volume, decreased radiotoxicity, and removal of fissile material. Many technological options have been proposed or explored, and each brings its own particular mix of wastes and environmental challenges.

Scaling up classification rule induction through parallel processing

The fast increase in the size and number of databases demands data mining approaches that are scalable to large amounts of data. This has led to the exploration of parallel computing technologies in order to perform data mining tasks concurrently using several processors. Parallelization seems to be a natural and cost-effective way to scale up data mining technologies. One of the most important of these data mining technologies is the classification of newly recorded data. This paper surveys advances in parallelization in the field of classification rule induction.

Atlantic meridional heat transports in two ocean reanalyes evaluated against the RAPID array

The Atlantic meridional overturning circulation in two versions of the NEMO ¼° global ocean model has been compared with the RAPID transport array at 26oN. Both model versions reproduce the mean MOC strength well although the Florida Straits flows differ because the pathway of the Gulf Stream is not strongly constrained at this resolution. Both models however have a mean meridional heat transport of 1.07PW, much lower than the 1.35PW from RAPID observations in Apr04-Oct07. Much of the heat transport discrepancy is due to lower transports in summer across the MidOcean (Bahamas-Africa) section, due to stronger southward geostrophic flows in the top 100m where the water is warmest. Seasonal thermocline changes increase temperature differences across the basin driving stronger geostrophic shear, but this effect is much weaker in the top 100m of the RAPID velocity data. The effect accounts for a reduction of 1.1Sv in MOC and 0.1PW in heat transports. The rest of the discrepancy comes from lower Ekman transports from using ERAInterim winds instead of QuikSCAT, a smaller zonally-varying “Eddy” heat transport component, estimated from repeat XBT sections in the observations, and the southward throughflow in the model. Other differences in depth structure of the model MOC and RAPID observations are described but have much less impact on heat transports.