Wetlands and the Water Framework Directive : key challenges for achieving good ecological status at the Anglesey and LLyn Fens SACs

The Water Framework Directive (WFD) requires assessment of water quality and quantity in groundwater bodies that are hydrologically linked to designated wetlands. The Anglesey and Llŷn Fens face chemical (e.g. nitrate) and quantitative (e.g. historic drainage) groundwater pressures. Hydrogeologists and ecologists have successfully worked together during the WFD classification process and impacts from diffuse nutrients have resulted in ‘poor’ chemical status for the surrounding Carboniferous Limestone groundwater body. Long term hydrological and chemical monitoring programs allow the assessment of baseline conditions, identification of trends and extreme climatic events (floods and droughts) possibly associated with our changing climate. Nutrient management plans, aimed at the reduction of inorganic fertilisers, must be agreed, implemented and monitored to ensure the return of the Anglesey and Llŷn Fens to favorable ecological condition and good groundwater chemical status. Key challenges include encouraging both ecologists and hydrogeologists to work together; continuing to work well with landowners and farmers; implementation of plans to reduce over application of inorganic fertilizers and to continue monitoring the Anglesey and Llŷn Fens as part of future climate change monitoring programs. If nothing is done to address these key challenges or the ‘after LIFE’ work is not supported there is a real risk of failure of targets associated with both the Water Framework Directive and Habitats Directive

On the Comparison of the Long Penetration Mode (LPM) Supersonic Counterflowing Jet to the Supersonic Screech Jet

The authors provide a brief overview of the classic tonal screech noise problem created by underexpanded supersonic jets, briefly describing the fluid dynamic-acoustics feedback mechanism that has been long established as the basis for this well-known aeroacoustics problem. This is followed by a description of the Long Penetration Mode (LPM) supersonic underexpanded counterflowing jet phenomenon which has been demonstrated in several wind tunnel tests and modeled in several computational fluid dynamics (CFD) simulations. The authors provide evidence from test and CFD analysis of LPM that indicates that acoustics feedback and fluid interaction seen in LPM are analogous to the aeroacoustics interactions seen in screech jets. Finally, the authors propose applying certain methodologies to LPM which have been developed and successfully demonstrated in the study of screech jets and mechanically induced excitation in fluid oscillators for decades. The authors conclude that the large body of work done on jet screech, other aeroacoustic phenomena, and fluid oscillators can have direct application to the study and applications of LPM counterflowing supersonic cold flow jets

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.

The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination

Effect of Biodiversity Changes in Disease Risk: Exploring Disease Emergence in a Plant-Virus System

The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species

Assessing Multi-Agent Reinforcement Learning Algorithms for Autonomous Sensor Resource Management

Unmanned aerial vehicles (UAVs) have applications in search and rescue operations and such operations could be more efficient by using appropriate artificial intelligence (AI) to enable a UAV agent to operate autonomously. Sensor resource management (SRM), which leverages capabilities across location intelligence, facilitates the efficient and effective use of UAVs and their sensors to complete a set of tasks. Furthermore, multiple UAVs, each with different sensor configurations, must be considered when maximizing mission effects. Instantiating operational autonomy for such teams requires considerable coordination. One AI approach relevant to this task is multi-agent reinforcement learning (MARL). However, MARL has seen limited prior use in SRM. This work evaluates the trade-space of MARL algorithms with respect to performing heterogeneous sensor resource management (SRM) tasks, considers the concept of evaluating MARL in a test and evaluation framework and compares a suit of algorithms with random and Bayesian hyperparameter optimization methods

Adiantum capillus-veneris (Maidenhair Fern) along the Vale of Glamorgan Coastline, South Wales, UK: a comparison of surveys over 30 years

Adiantum capillus-veneris (Maidenhair Fern), occurs on all continents except the Antarctic, and is considered stable worldwide (Lansdown & Bilz, 2013). In the UK the vascular plants red data list reports the status of A. capillusveneris as of ‘least concern’ (Cheffings et al., 2005). Native populations occur mainly in crevices or on tufa deposits, limited to a few scattered coastal localities (Stewart et al., 1994). Wales is home to about 25% of the UK’s native population (Dines, 2008) mainly concentrated along the Vale of Glamorgan Coastline and to a lesser extent in Pembrokeshire and Carmarthenshire. The earliest record (Llwyd, 1698), at Jacksons Bay, Barry Island suggest populations have been persistent for at least 300 years. Historical records for A. capillus- veneris can also be found for Porthkerry; 1838, Dunraven Bay; 1849, Aberthaw; 1862 and Font-y-Gary, 1927 and A. capillus-veneris is still present at all of the aforementioned sites. A. capillus-veneris’s natural habitat in South Wales is primarily restricted to active post glacial tufaceous cliff face seepages which are frequently, but not entirely, associated with the Jurassic Lias bedrock that defines the Vale of Glamorgan ‘Heritage Coast’. The interbedded nature of the Jurassic Lias rocks, with relatively impermeable, thinly interbedded limestones and calcareous mudstones (Wilson et al., 1990), favours the slow diffuse seepage of groundwater across large areas of cliff face supporting the formation of tufa. Tufa forms when groundwater, supersaturated with calcium carbonate dissolved from the bedrock aquifer, re-deposits the material on contact with the atmosphere. Three surveys across the Vale of Glamorgan coastline have been undertaken, the first by Peter S. Jones (1983-4) then Kate Pryor 1996 (reported in Pryor, 2001) and again in 2015 by the authors. Molecular studies of several populations along the coast (Pryor, 2001 & Pryor et al., 2001) provide insight into the genetics of satellite populations, however further discussion of this is outside of the scope of this note. The aim of this survey was to collate and compare the locations of populations recorded over the last 30 years. It is hoped that this will serve as a useful baseline for repeat surveys in the future