Perfluoroarene-based peptide macrocycles that inhibit the Nrf2/Keap1 interaction

The Nrf2/Keap1 interaction is a target in the development of new therapeutic agents, where inhibition of the interaction activates Nrf2 and leads to the generation of downstream anti-inflammatory effects. Peptides that mimic the β-turn in the Keap1 active site and are constrained by a disulfide bridge have high affinity for Keap1 but no intracellular activity. The introduction of a perfluoroalkyl- bridging group to constrain the peptides, coupled with glutamic acid to proline replacement leads to a new peptide with a Ki of 6.1 nM for the Nrf2/Keap1 binding interaction, although this does not translate into intracellular activity

An approach to the assessment of change in the numbers of Canada Branta canadensis and Greylag Geese Anser anser in southern Britain

Population change in geese was assessed using an approach that requires a relatively small sampling effort. During the 1999 breeding season a survey was carried out to determine if the numbers of introduced Canada and re-established Greylag Geese in southern Britain had changed since 1988–91 and whether any change had occurred in areas with previously high or low Canada Goose densities. A randomized stratified sample of 246 tetrads from the 24 156 tetrads covered between 1988–91 in this area, as part of the New Atlas of Breeding Birds, were resurveyed. Eight habitat cate- gories were used in the stratification and were based on 1-km-square summary data obtained from the CEH Land Cover Map of Great Britain (water cover and urbanization) and LANDCLASS stratification (upland/lowland). The five habitat categories with the highest densities of Canada Geese and the greatest variance in numbers were sampled. Between 1989 and 1999, the number of Canada Geese on land with over 5% water cover and on lowland with some water cover increased by on average 156%, an average rate of increase of 9.9% per annum. Southern Britain probably now holds a minimum of 82 000 Canada Geese. Between 1989 and 1999, the number of Greylag Geese on land with over 5% water cover and on lowland with some water cover increased by on average 214%, an average rate of increase of 12% per annum. Southern Britain probably now holds a minimum of 30 000 Greylag Geese. Maximum densities of Canada Geese may have been reached in high-density habitats but their numbers are still increasing very rapidly. Greylag Geese are increasing even more rapidly

Developing an integrated approach to understanding the effects of climate change and other environmental alterations at a flyway level

The environmental consequences of global climate change are predicted to have their greatest effect at high latitudes and have great potential to impact fragile tundra ecosystems. The Arctic tundra is a vast biodiversity resource and provides breeding areas for many migratory geese. Importantly, tundra ecosystems also currently act as a global carbon “sink”, buffering carbon emissions from human activities. In January 2003, a new three year project was implemented to understand and model the interrelationships between goose population dynamics, conservation, European land use/agriculture and climate change. A range of potential future climate and land-use scenarios will be applied to the models and combined with information from field experiments on grazing and climate change in the Arctic. This paper describes the content of the research programme as well as issues in relation to engaging stakeholders with the project

Developing an integrated approach to understanding the effects of climate change and other environmental alterations at a flyway level

The environmental consequences of global climate change are predicted to have their greatest effect at high latitudes and have great potential to impact fragile tundra ecosystems. The Arctic tundra is a vast biodiversity resource and provides breeding areas for many migratory geese. Importantly, tundra ecosystems also currently act as a global carbon “sink”, buffering carbon emissions from human activities. In January 2003, a new three year project was implemented to understand and model the interrelationships between goose population dynamics, conservation, European land use/agriculture and climate change. A range of potential future climate and land-use scenarios will be applied to the models and combined with information from field experiments on grazing and climate change in the Arctic. This paper describes the content of the research programme as well as issues in relation to engaging stakeholders with the project

Neurochemical enhancement of conscious error awareness

How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited.Weconducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors

Non-breeding and nests without eggs in the Lesser Black-backed Gull.

Estimates of the number of breeding Lesser Black-backed Gulls Larus fuscus at the Tarnbrook Fell gullery, Lancashire, have been made from annual counts of nests since 1981. During all of these surveys, the mean percentage of nests which did not contain eggs has been remarkably constant from year to year (54%± 1.9%). A study of specific nests at the colony in 1992 showed that the great majority of these “empty” nests did not subsequently receive eggs. in 1993, a study of a sample of territory-holding gulls was made on a 0.41-ha study plot to investigate and to quantify the occurrence of empty nests. Of the 62 pairs that defended a territory and constructed a complete nest, 27% subsequently failed to produce eggs. These birds attended their territory as a pair significantly less frequently than pairs that produced clutches and achieved significantly fewer apparently successful mountings. Sixty percent of pairs constructed more than one nest, and 58% of all nests built received no eggs. The construction of empty nests was not found to be related to the density of nesting gulls. Since 1981, estimates of the number of gulls in the colony have been based on the assumption that one nest represents one pair of gulls. This has been shown not to be the case, and a correction multiplier of 0.61 must be applied to counts of nests at the colony to obtain an estimate of the number of breeding gulls

Uncovering the Neural Signature of Lapsing Attention: Electrophysiological Signals Predict Errors up to 20 s before They Occur

The extent to which changes in brain activity can foreshadow human error is uncertain yet has important theoretical and practical implications. The present study examined the temporal dynamics of electrocortical signals preceding a lapse of sustained attention. Twenty-one participants performed a continuous temporal expectancy task, which involved continuously monitoring a stream of regularly alternating patterned stimuli to detect a rarely occurring target stimulus whose duration was 40% longer. The stimulus stream flickered at a rate of 25 Hz to elicit a steady-state visual-evoked potential (SSVEP), which served as a continuous measure of basic visual processing. Increasing activity in the band (8 –14 Hz) was found beginning20 s before a missed target. This was followed by decreases in the amplitude of two event-related components over a short pretarget time frame: the frontal P3 (3– 4 s) and contingent-negative variation (during the target interval). In contrast, SSVEP amplitude before hits and misses was closely matched, suggesting that the efficacy of ongoing basic visual processing was unaffected. Our results show that the specific neural signatures of attentional lapses are registered in the EEG up to 20 s before an error

The Sulfur-Iodine Cycle: Process Analysis and Design Using Comprehensive Phase Equilibrium Measurements and Modeling

Of the 100+ thermochemical hydrogen cycles that have been proposed, the Sulfur-Iodine (S-I) Cycle is a primary target of international interest for the centralized production of hydrogen from nuclear power. However, the cycle involves complex and highly nonideal phase behavior at extreme conditions that is only beginning to be understood and modeled for process simulation. The consequence is that current designs and efficiency projections have large uncertainties, as they are based on incomplete data that must be extrapolated from property models. This situation prevents reliable assessment of the potential viability of the system and, even more, a basis for efficient process design. The goal of this NERI award (05-006) was to generate phase-equilibrium data, property models, and comprehensive process simulations so that an accurate evaluation of the S-I Cycle could be made. Our focus was on Section III of the Cycle, where the hydrogen is produced by decomposition of hydroiodic acid (HI) in the presence of water and iodine (I2) in a reactive distillation (RD) column. The results of this project were to be transferred to the nuclear hydrogen community in the form of reliable flowsheet models for the S-I process. Many of the project objectives were achieved. At Clemson University, a unique, tantalum-based, phase-equilibrium apparatus incorporating a view cell was designed and constructed for measuring fluid-phase equilibria for mixtures of iodine, HI, and water (known as HIx) at temperatures to 350 °C and pressures to 100 bar. Such measurements were of particular interest for developing a working understanding of the expected operation of the RD column in Section III. The view cell allowed for the IR observation and discernment of vapor-liquid (VL), liquid-liquid, and liquid-liquid-vapor (LLVE) equilibria for HIx systems. For the I2-H2O system, liquid-liquid equilibrium (LLE) was discovered to exist at temperatures up to 310-315 °C, in contrast to the models and predictions of earlier workers. For the I2-HI-H2O ternary, LLE and LLVE were all observed for the first time at temperatures of 160 and 200 °C. Three LLE tie-lines were measured at 160 °C, and preliminary indications are that the underlying phase behavior could result in further improvements in the performance of the S-I Cycle. Unfortunately, these new results were obtained too late in the project to be incorporated into the modeling and simulation work described below. At the University of Virginia, a uniquely complete and reliable model was developed for the thermodynamic properties of HIx, covering the range of conditions expected for the separation of product hydrogen and recycled iodine in the RD column located in Section III. The model was validated with all available property spectroscopy data. The results provide major advances over prior understanding of the chemical speciation involved. The model was implemented in process simulation studies of the S-I Cycle, which showed improvement in energy efficiency to 42%, as well as significantly smaller capital requirements due to lower pressure operation and much smaller equipment sizes. The result is that the S-I Cycle may be much more economically feasible than was previously thought. If both the experimental and modeling work described above were to be continued to ultimate process optimization, both the American public and the global community would benefit from this alternative energy source that does not produce carbon emissions

The Evolution of Early-Type Galaxies in Distant Clusters

We present results from an optical-IR photometric study of early-type galaxies in 19 galaxy clusters out to z=0.9. The galaxy sample is selected on the basis of morphologies determined from HST WFPC2 images, and is photometrically defined in the K-band to minimize redshift-dependent selection biases. The optical-IR colors of the early-type cluster galaxies become bluer with increasing redshift in a manner consistent with the passive evolution of an old stellar population formed at an early cosmic epoch. The degree of color evolution is similar for clusters at similar redshift, and does not depend strongly on the optical richness or X-ray luminosity of the cluster, suggesting that the history of early-type galaxies is relatively insensitive to environment. The slope of the color-magnitude relationship shows no significant change out to z=0.9, providing evidence that it arises from a correlation between galaxy mass and metallicity, not age. Finally, the intrinsic scatter in the optical-IR colors is small and nearly constant with redshift, indicating that the majority of giant, early-type galaxies in clusters share a common star formation history, with little perturbation due to uncorrelated episodes of later star formation. Taken together, our results are consistent with models in which most early-type galaxies in rich clusters are old, formed the majority of their stars at high redshift in a well-synchronized fashion, and evolved quiescently thereafter.Comment: 55 pages, 24 figures, uses AASTeX. Accepted for publication in The Astrophysical Journa