Antarctic crustacean grazer assemblages exhibit resistance following exposure to decreased pH

Anthropogenic atmospheric CO2 concentrations are increasing rapidly, resulting in declining seawater pH (ocean acidification). The majority of ocean acidification research to date has focused on the effects of decreased pH in single-species experiments. To assess how decreased pH may influence natural macroalgal-grazer assemblages, we conducted a mesocosm experiment with the common, chemically defended Antarctic brown macroalga Desmarestia menziesii and natural densities of its associated grazer assemblage, predominantly amphipods. Grazer assemblages were collected from the immediate vicinity of Palmer Station (64°46'S, 64°03'W) in March 2013. Assemblages were exposed for 30 days to three levels of pH representing present-day mean summer ambient conditions (pH 8.0), predicted near-future conditions (2100, pH 7.7), and distant-future conditions (pH 7.3). A significant difference was observed in the composition of mesograzer assemblages in the lowest pH treatment (pH 7.3). The differences between assemblages exposed to pH 7.3 and those maintained in the other two treatments were driven primarily by decreases in the abundance of the amphipod Metaleptamphopus pectinatus with decreasing pH, reduced copepod abundance at pH 7.7, and elevated ostracod abundance at pH 7.7. Generally, the assemblages maintained at pH 7.7 were not significantly different from those at ambient pH, demonstrating resistance to short-term decreased pH. The relatively high prevalence of generalist amphipods may have contributed to a net stabilizing effect on the assemblages exposed to decreased pH. Overall, our results suggest that crustacean grazer assemblages associated with D. menziesii, the dominant brown macroalgal species of the western Antarctic Peninsula, may be resistant to short-term near-future decreases in seawater pH.

Do R&D strategies in high-tech sectors differ from those in low-tech sectors? An alternative approach to testing the pooling assumption

Most studies investigating the determinants of R&D investment consider pooled estimates. However, if the parameters are heterogeneous, pooled coefficients may not provide reliable estimates of individual industry effects. Hence pooled parameters may conceal valuable information that may help target government tools more efficiently across heterogeneous industries. There is little evidence to date on the decomposition of the determinants of R&D investment by industry. Moreover, the existing work does not distinguish between those R&D determinants for which pooling may be valid and those for which it is not. In this paper, we test the pooling assumption for a panel of manufacturing industries and find that pooling is valid only for output fluctuations, adjustment costs and interest rates. Implementing the test results into our model, we find government funding is significant only for low-tech R&D. Foreign R&D and skilled labour matter only in high-tech sectors. These results suggest important implications for R&D policy.

Impurity profiling and synthesis of precursors to the hallucinogenic amphetamine DOB

DOB (4‐bromo‐2,5‐dimethoxyamphetamine) is a newly emerging hallucinogenic amphetamine that sparked serious health warnings in Ireland, following its first seizure back in 2003. Known more commonly as “snowball”, this drug is highly potent and may be used as a substitute to ecstasy (MDMA) and lysergic acid diethylamide (LSD). To date, the work carried out on the impurity profiling of DOB is limited in comparison to amphetamine, methamphetamine and MDMA. In this work, the impurity profile of 4‐bromo‐2,5‐dimethoxyphenyl‐2‐propanone (4‐Br‐2,5‐P2P) is explored. This ketone is a direct precursor to DOB. Its more versatile non‐bromo analogue, 2,5‐ dimethoxyphenyl‐2‐propanone (2,5‐P2P) is also examined, as in addition to DOB, it may be used in the synthesis of a range of several other hallucinogenic amphetamines. A number of different routes to both 2,5‐P2P and 4‐Br‐2,5‐P2P were investigated. For each of these routes, the impurities produced were carefully isolated. Following isolation, the impurities were fully characterised (by 1H‐NMR/13C‐NMR spectroscopy, IR, MS), in order to aid structure elucidation. Compounds not easily resolved by flash column chromatography were analysed by LC‐MS and/or independently synthesised for the purpose of attaining reference standards. Adaptation of the well‐known ‘phenylacetic acid route’ to synthesis of both 2,5‐P2P and 4‐Br‐2,5‐P2P, was found to provide low yields of the expected ketone products. Four impurities were isolated during the preparation of both ketones. The yield of one of these impurities (possessing a dibenzylketone core), was greatly influenced by the amount of acetic anhydride reagent used during the reaction. Having carried out the reaction with several different equivalents of acetic anhydride, it was found that formation of the ‘dibenzylketone’ could not be eliminated. This may increase its likelihood of being detected in the final drug product. The ‘Darzens route’, having very recently emerged as a synthetic route to amphetamine and MDMA precursors, was discovered to be a viable route for manufacture of 2,5‐P2P and 4‐Br‐2,5‐P2P. Despite execution of the reaction being more tedious, the route provides superior yields (≈50–60%) to those achieved using the ‘phenylacetic acid route’ (≈35–38%). Incorporation of a bromine atom (at the aromatic 4‐position) is required at some stage during synthesis of DOB. The bromination of many intermediates/starting materials was therefore also examined in detail. Bromination of the acid starting material 2,5‐dimethoxyphenylacetic acid (2,5‐PAA) was found to be clean and high yielding. This was in stark contrast to the bromination of the benzaldehyde starting material, the ketone precursor 2,5‐P2P and the dibenzylketone‐based impurity. Numerous brominated products were isolated from each of these reactions, many of which were novel compounds, and previously unreported as impurities in the literature. The unpredictable/nondescript nature of these brominations is likely to have a significant impact on the impurity profile of illicitly produced DOB.

Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions.

BACKGROUND: Efficient effort expenditure to obtain rewards is critical for optimal goal-directed behavior and learning. Clinical observation suggests that individuals with autism spectrum disorders (ASD) may show dysregulated reward-based effort expenditure, but no behavioral study to date has assessed effort-based decision-making in ASD. METHODS: The current study compared a group of adults with ASD to a group of typically developing adults on the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based decision-making. In this task, participants were provided with the probability of receiving a monetary reward on a particular trial and asked to choose between either an "easy task" (less motoric effort) for a small, stable reward or a "hard task" (greater motoric effort) for a variable but consistently larger reward. RESULTS: Participants with ASD chose the hard task more frequently than did the control group, yet were less influenced by differences in reward value and probability than the control group. Additionally, effort-based decision-making was related to repetitive behavior symptoms across both groups. CONCLUSIONS: These results suggest that individuals with ASD may be more willing to expend effort to obtain a monetary reward regardless of the reward contingencies. More broadly, results suggest that behavioral choices may be less influenced by information about reward contingencies in individuals with ASD. This atypical pattern of effort-based decision-making may be relevant for understanding the heightened reward motivation for circumscribed interests in ASD.

Reframing Chinese animation: from classicism to postmodernism in post-1949 non-commercial Chinese animated films

This thesis focuses on Chinese non-commercial animated films produced from 1949 to date, with the aim of remapping and reframing Chinese animation in the light of existing theories, critiques, and frameworks drawn from studies in animation, film, and screen media. I suggest that Chinese animation has experienced three aesthetic transformations since 1949, primarily influenced by traditional Chinese culture, by Western modernist art and literature and, most recently, by postmodernism, respectively. Thus, the research traces and thoroughly investigates these three distinctive phases of Chinese animation in chronological order, from the classical period (1950s– 1980s) to modernism (1980s–2000s) and postmodernism (after 2000s). More in detail, I first rethink and re-evaluate the success of classical Chinese animation and the Chinese school of animation and, at the same time, I explore the influence of the political situation of the time on Chinese animation. Through careful analysis of A Da (1934–87) and other Chinese animators’ practices and theory, then, I argue that a remarkable modernist transformation took place in Chinese animation between the 1980s and 2000s, mainly driven by Western modernism and the Chinese “cultural fever” movement. Finally, through a discussion of the latest non-commercial animations produced after 2005, and especially those of Bu Hua (1973– ), for the first time I classify and theorize contemporary Chinese animations within a postmodern framework. By reframing existing views and broadening the scope of the analysis to encompass new areas and frameworks, this thesis aims to provide the reader with a comprehensive and systematic understanding of post-1949 Chinese animation and to offer an original contribute to scholarship, also working as a starting point for further research in this area.

E-RUN version 1.1: Observational gridded runoff estimates for Europe, link to data in NetCDF format (69 MB)

River runoff is an essential climate variable as it is directly linked to the terrestrial water balance and controls a wide range of climatological and ecological processes. Despite its scientific and societal importance, there are to date no pan-European observation-based runoff estimates available. Here we employ a recently developed methodology to estimate monthly runoff rates on regular spatial grid in Europe. For this we first assemble an unprecedented collection of river flow observations, combining information from three distinct data bases. Observed monthly runoff rates are first tested for homogeneity and then related to gridded atmospheric variables (E-OBS version 12) using machine learning. The resulting statistical model is then used to estimate monthly runoff rates (December 1950 - December 2015) on a 0.5° x 0.5° grid. The performance of the newly derived runoff estimates is assessed in terms of cross validation. The paper closes with example applications, illustrating the potential of the new runoff estimates for climatological assessments and drought monitoring.

E-RUN version 1.0: Observational gridded runoff estimates for Europe, link to data in NetCDF format (68 MB)

River runoff is an essential climate variable as it is directly linked to the terrestrial water balance and controls a wide range of climatological and ecological processes. Despite its scientific and societal importance, there are to date no pan-European observation-based runoff estimates available. Here we employ a recently developed methodology to estimate monthly runoff rates on regular spatial grid in Europe. For this we first collect an unprecedented collection of river flow observations, combining information from three distinct data bases. Observed monthly runoff rates are first tested for homogeneity and then related to gridded atmospheric variables (E-OBS version 11) using machine learning. The resulting statistical model is then used to estimate monthly runoff rates (December 1950-December 2014) on a 0.5° × 0.5° grid. The performance of the newly derived runoff estimates is assessed in terms of cross validation. The paper closes with example applications, illustrating the potential of the new runoff estimates for climatological assessments and drought monitoring.

A suite of global, cross-scale topographic variables for environmental and biodiversity modeling, links to files in GeoTIFF format

Topographic variation, the spatial variation in elevation and terrain features, underpins a myriad of patterns and processes in geography and ecology and is key to understanding the variation of life on the planet. The characterization of this variation is scale-dependent, i.e. it varies with the distance over which features are assessed and with the spatial grain (grid cell resolution) of analysis. A fully standardized and global multivariate product of different terrain features has the potential to support many large-scale basic research and analytical applications, however to date, such technique is unavailable. Here we used the digital elevation model products of global 250 m GMTED and near-global 90 m SRTM to derive a suite of topographic variables: elevation, slope, aspect, eastness, northness, roughness, terrain roughness index, topographic position index, vector ruggedness measure, profile and tangential curvature, and 10 geomorphological landform classes. We aggregated each variable to 1, 5, 10, 50 and 100 km spatial grains using several aggregation approaches (median, average, minimum, maximum, standard deviation, percent cover, count, majority, Shannon Index, entropy, uniformity). While a global cross-correlation underlines the high similarity of many variables, a more detailed view in four mountain regions reveals local differences, as well as scale variations in the aggregated variables at different spatial grains. All newly-developed variables are available for download at http://www.earthenv.org and can serve as a basis for standardized hydrological, environmental and biodiversity modeling at a global extent.

Temporal differences across a bio-geographical boundary reveal slow response of sub-littoral benthos to climate change

The English Channel is located at the biogeographical boundary between the northern Boreal and southern Lusitanian biozones and therefore represents an important area to study the effects of global warming on marine organisms. While the consequences of climatic change in the western English Channel have been relatively well documented for fish, plankton and inter-tidal benthic communities, data highlighting the same effects on the distribution of sub-littoral benthic organisms does, to date, not exist. The present study resurveyed a subset of sites originally surveyed from 1958 to 1959 along the UK coast of the English Channel. The main aims of this resurvey were to describe the present status of benthic communities and to investigate potential temporal changes, in particular distributional changes in western stenothermal ‘cold’ water and southern Lusitanian ‘warm’ water species. The increase in water temperature observed since the historic survey was predicted to have caused a contraction in the distribution of cold water species and an extension in the distribution of warm water species. The temporal comparison did not show any clear broad-scale distributional changes in benthic communities consistent with these predictions. Nevertheless, 2 warm water species, the sting winkle Ocenebra erinacea and the introduced American slipper limpet Crepidula fornicata, did show range extensions and increased occurrence, possibly related to climatic warming. Similarly, warm water species previously not recorded by the historic survey were found. The absence of broad-scale temporal differences in sub-tidal communities in response to climatic warming has been reported for other areas and may indicate that these communities respond far more slowly to environmental changes compared to plankton, fish and inter-tidal organisms.

Temporal differences across a bio-geographical boundary reveal slow response of sub-littoral benthos to climate change

The English Channel is located at the biogeographical boundary between the northern Boreal and southern Lusitanian biozones and therefore represents an important area to study the effects of global warming on marine organisms. While the consequences of climatic change in the western English Channel have been relatively well documented for fish, plankton and inter-tidal benthic communities, data highlighting the same effects on the distribution of sub-littoral benthic organisms does, to date, not exist. The present study resurveyed a subset of sites originally surveyed from 1958 to 1959 along the UK coast of the English Channel. The main aims of this resurvey were to describe the present status of benthic communities and to investigate potential temporal changes, in particular distributional changes in western stenothermal ‘cold’ water and southern Lusitanian ‘warm’ water species. The increase in water temperature observed since the historic survey was predicted to have caused a contraction in the distribution of cold water species and an extension in the distribution of warm water species. The temporal comparison did not show any clear broad-scale distributional changes in benthic communities consistent with these predictions. Nevertheless, 2 warm water species, the sting winkle Ocenebra erinacea and the introduced American slipper limpet Crepidula fornicata, did show range extensions and increased occurrence, possibly related to climatic warming. Similarly, warm water species previously not recorded by the historic survey were found. The absence of broad-scale temporal differences in sub-tidal communities in response to climatic warming has been reported for other areas and may indicate that these communities respond far more slowly to environmental changes compared to plankton, fish and inter-tidal organisms.

Macroalgae contribute to the diet of Patella vulgata from contrasting conditions of latitude and wave exposure in the UK

Analysis of gut contents and stable isotope composition of intertidal limpets (Patella vulgata) showed a major contribution of macroalgae to their diet, along with microalgae and invertebrates. Specimens were collected in areas with limited access to attached macroalgae, suggesting a major dietary component of drift algae. Gut contents of 480 animals from 2 moderately wave-exposed and 2 sheltered rocky shores in each of 2 regions (western Scotland, 55-56°N; and southwest England, 50°N), were analysed in 2 years (n = 30 site-1 yr-1). The abundance of microalgae, macroalgae and invertebrates within the guts was quantified using categorical abundance scales. Gut content composition was compared among regions and wave exposure conditions, showing that the diet of P. vulgata changes with both wave exposure and latitude. Microalgae were most abundant in limpet gut contents in animals from southwestern sites, whilst leathery/corticated macroalgae were more prevalent and abundant in limpets from sheltered and northern sites. P. vulgata appears to have a more flexible diet than previously appreciated, and these keystone grazers consume not only microalgae, but also large quantities of macroalgae and small invertebrates. To date, limpet grazing studies have focussed on their role in controlling recruitment of macroalgae by feeding on microscopic propagules and germlings. Consumption of adult algae suggests that P. vulgata may also directly control the biomass of attached macroalgae on the shore, whilst consumption of drift algae indicates that the species may play important roles in coupling subtidal and intertidal production.

Macroalgae contribute to the diet of Patella vulgata from contrasting conditions of latitude and wave exposure in the UK

Analysis of gut contents and stable isotope composition of intertidal limpets (Patella vulgata) showed a major contribution of macroalgae to their diet, along with microalgae and invertebrates. Specimens were collected in areas with limited access to attached macroalgae, suggesting a major dietary component of drift algae. Gut contents of 480 animals from 2 moderately wave-exposed and 2 sheltered rocky shores in each of 2 regions (western Scotland, 55-56°N; and southwest England, 50°N), were analysed in 2 years (n = 30 site-1 yr-1). The abundance of microalgae, macroalgae and invertebrates within the guts was quantified using categorical abundance scales. Gut content composition was compared among regions and wave exposure conditions, showing that the diet of P. vulgata changes with both wave exposure and latitude. Microalgae were most abundant in limpet gut contents in animals from southwestern sites, whilst leathery/corticated macroalgae were more prevalent and abundant in limpets from sheltered and northern sites. P. vulgata appears to have a more flexible diet than previously appreciated, and these keystone grazers consume not only microalgae, but also large quantities of macroalgae and small invertebrates. To date, limpet grazing studies have focussed on their role in controlling recruitment of macroalgae by feeding on microscopic propagules and germlings. Consumption of adult algae suggests that P. vulgata may also directly control the biomass of attached macroalgae on the shore, whilst consumption of drift algae indicates that the species may play important roles in coupling subtidal and intertidal production.

Peptide Therapeutics and the Pharmaceutical Industry: Barriers Encountered Translating from the Laboratory to Patients

Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or for prostate and breast cancer,and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T. Research is also focusing on improving the biostability of peptides. This is achieved through a number of mechanisms ranging from replacement of naturally occurring L-amino acid enantiomers with D-amino acid forms, lipidation, peptidomimetics, N-methylation, cyclization and exploitation of carrier systems. The development of self-assembling peptides are paving the way for sustained release peptide formulations and already two such licensed examples exist, lanreotide and octreotide. The versatility and tunability of peptide-based products is resulting in increased translation of peptide therapies, however significant challenges remain with regard to their wider implementation. This review highlights some of the notable peptide therapeutics discovered to date and the difficulties encountered by the pharmaceutica lindustry in translating these molecules to the clinical setting for patient benefit, providing some possible solutions to the most challenging barriers. 

Basalt Fibre Reinforced Polymer Strengthening of Normal Strength Reinforced Concrete Floor Slabs Subject to Arching Effects

With ever increasing demands to strengthen existing reinforced concrete structures to facilitate higher loading due to change of use and to extend service lifetime, the use of fibre reinforced polymers (FRPs) in structural retrofitting offers an opportunity to achieve these aims. To date, most research in this area has focussed on the use of glass fibre reinforced polymer (GFRP) and carbon fibre reinforced polymer (CFRP), with relatively little on the use of basalt fibre reinforced polymer (BFRP) as a suitable strengthening material. In addition, most previous research has been carried out using simply supported elements, which have not considered the beneficial influence of in-plane lateral restraint, as experienced within a framed building structure. Furthermore, by installing FRPs using the near surface mounted (NSM) technique, disturbance to the existing structure can be minimised.
This paper outlines BFRP NSM strengthening of one third scale laterally restrained floor slabs which reflect the inherent insitu compressive membrane action (CMA) in such slabs. The span-to-depth ratios of the test slabs were 20 and 15 and all were constructed with normal strength concrete (~40N/mm2) and 0.15% steel reinforcement. 0.10% BFRP was used in the retrofitted samples, which were compared with unretrofitted control samples. In addition, the bond strength of BFRP bars bonded into concrete was investigated over a range of bond lengths with two different adhesive thicknesses. This involved using an articulated beam arrangement in order to establish optimum bond characteristics for use in strengthening slab samples.

New Framework and Metrics for Economic Evaluation of Medical Technology in the Presence of Heterogeneity and Its Application to the Evaluation of Bariatric Surgery

Thesis (Ph.D.)--University of Washington, 2016-07