Botanical rejuvenation of field margins and benefits for invertebrate fauna on a drystock farm in County Longford

peer-reviewedThis study investigates methods to rejuvenate the fl ora of previously degraded fi eld margins on a pastoral farm in County Longford. We also assess the effects of individual treatments on the abundance of various orders of invertebrates recorded within the experimental plots. Field margin treatments were 1.5m-wide unfenced control margins, 1.5m-wide fenced margins or 3.5m-wide fenced margins. Nutrient inputs were excluded from all of the experimental plots. The botanical composition of the plots was examined on four occasions between 2002 and 2004 using permanent, nested quadrats. Emergence traps were used to measure invertebrate abundance within treatment plots and the main sward. Results indicated that 1) exclusion of nutrient inputs had a positive effect on plant species richness within the fi eld margins; 2) plant species richness decreased with increased distance from the hedgerow; 3) herb species richness was greatest in the 1.5m closest to the hedgerow; 4) greater abundance of invertebrates occurred within the 3.5m-wide margins; 5) successful control of Pteridium aquilinum was achieved through spot treatment with the selective herbicide ‘Asulox’; and 6) a combination of management techniques such as cutting and grazing is likely to enhance plant species richness and facilitate the structural diversity of vegetation that is necessary for many invertebrate taxa.Teagasc Walsh Fellowship Programm

N-Cyclo­pentyl-N-(3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide

The title mol­ecule, C16H19NO2, consists of an indane moiety, which is connected through an N atom to an acetamide group and a cyclo­pentane ring. The N atom adopts planar triangular geometry. Inter­molecular inter­actions, such as π–π stacking or hydrogen bonding, were not observed

Traditional Chinese Medicine: From Aqueous Extracts to Therapeutic Formulae

Traditional Chinese medicine (TCM) is one of the most established systems of medicine in the world. The therapeutic formulae used in TCM are frequently derived from aqueous decoctions of single plants or complex multicomponent formulae. There are aspects of plant cultivation and preparation of decoction pieces that are unique to TCM. These include Daodi cultivation, which is associated with high quality medicinal plant material that is grown in a defined geographical area, and Paozhi processing where the decoction pieces can be treated with excipients and are processed, which may fundamentally change the nature of the chemical metabolites. Therefore, a single plant part, processed in a variety of different ways, can each create a unique medicine. The quality of TCM materials, their safety and therapeutic efficacy are of critical importance. The application of metabolomic and chemometric techniques to these complex and multicomponent medicines is of interest to understand the interrelationships between composition, synergy and therapeutic activity. In this chapter, we present a short history of TCM, detail the role of Daodi and Paozhi in the generation of therapeutic formulae and look at the international practices and methodologies currently in use to ensure their sustainable production, quality, safety and efficacy

Progress of the PRINCIPLE project: promoting MT for Croatian, Icelandic, Irish and Norwegian

This paper updates the progress made on the PRINCIPLE project, a 2-year action funded by the European Commission un-der the Connecting Europe Facility (CEF) programme. PRINCIPLE focuses on col-lecting high-quality language resources for Croatian, Icelandic, Irish and Norwe-gian, which have been identified as low-resource languages, especially for build-ing effective machine translation (MT) systems. We report initial achievements of the project and ongoing activities aimed at promoting the uptake of neural MT for the low-resource languages of the project

Ideating XAI: An Exploration of User’s Mental Models of an AI-Driven Recruitment System Using a Design Thinking Approach

Artificial Intelligence (AI) is playing an important role in society including how vital, often life changing decisions are made. For this reason, interest in Explainable Artificial Intelligence (XAI) has grown in recent years as a means of revealing the processes and operations contained within what is often described as a black box, an often-opaque system whose decisions are difficult to understand by the end user. This paper presents the results of a design thinking workshop with 20 participants (computer science and graphic design students) where we sought to investigate users\u27 mental models when interacting with AI systems. Using two personas, participants were asked to empathise with two end users of an AI driven recruitment system, identify pain points in a user’s experience and ideate on possible solutions to these pain points. These tasks were used to explore the user’s understanding of AI systems, the intelligibility of AI systems and how the inner workings of these systems might be explained to end users. We discovered that visual feedback, analytics, and comparisons, feature highlighting in conjunction with factual, counterfactual and principal reasoning explanations could be used to improve user’s mental models of AI systems

Bioactive Indanes: Proof of Concept Study for Enantioselective Synthetic Routes to PH46A, a New Potential Anti-inflammation Agent

PH46A is a single enantiomer and a member of the 1,2-indane dimer family. It has two contiguous stereogenic centers with S,S configurations, one of which being a quaternary center, which has been developed as a clinical candidate for the treatment of inflammatory and autoimmune conditions. The current synthetic route to PH46A involves the generation of an unwanted enantiomer (R,R)-7, thus reducing the final yield significantly. Therefore, we have investigated potential alternatives to improve the efficiency of this synthesis. The first phase of the study has demonstrated proof of principle for a chiral alkylation of ketone 3 using phase-transfer catalysis, providing a key intermediate ketone (S)-4. The parent alkaloids required for the synthesis of PH46A, quinine or cinchonidine, have also been identified. Promising enantiomeric excesses of up to 50% have been achieved to date, and the use of an alternative substrate, unsaturated ketone 9, has also opened up further avenues for optimisation in future studies. The second part of the study involved preliminary screening the effects of a panel of hydrolase enzymes on (rac)-4 in order to identify a potential chemo-enzymatic route to optimise the introduction of chirality into PH46A at early stage of the synthesis. The hydrolase module has also yielded positive results; enzyme AH-46 with MtBE providing a selectivity factor of 8.4 with enantiomeric excess of 77%. Overall, positive results were obtained in this proof of concept study described herein. It is believed that conditions of both chiral PTC alkylation and biocatalytic hydrolysis could be optimised to further enhance the selectivity and improve the overall yield. This work is currently ongoing

Practical use of the multiple breath washout test in children: biological variability in health and disease

The Multiple Breath Washout (MBW) test is increasingly being recognised as a sensitive method of detecting early small airways lung disease. Indices of MBW include lung clearance index (LCI), Scond and Sacin. Factors that affect MBW variability have not been fully established. This thesis presents five studies which examine MBW repeatability in children with and without cystic fibrosis (CF) or asthma. MBW was performed using 0.2% sulphur hexafluoride and the modified Innocor (Innovision). Testing was performed at the Clinical Research Facility of the Royal Hospital for Sick Children in Edinburgh. (1) MBW and spirometry were performed in children with and without CF (n=20 in each group), initially while sitting and then 30 minutes after assuming a supine posture. LCI was found to significantly rise on lying supine in healthy children (p<0.01) and children with CF (p=0.03). (2) Thirty two children with CF performed MBW and spirometry on four study visits, results were correlated with findings from high resolution chest computed tomography scans taken on the first visit. LCI showed the strongest correlation with extent and severity of bronchiectasis (r=0.66, p<0.01 and r=0.69, p<0.01 respectively). Variability of LCI was similar to FEV1 over the 4 visits. (3) MBW and spirometry of 66 healthy children were compared to 63 children with stable asthma; lung function of asthmatic children was related to symptoms and medication use. LCI was higher in the asthmatic group (6.7 vs 6.3, p<0.01); within the asthmatic group LCI was significantly higher if asthma was less well controlled (p=0.02). (4) Children with and without asthma (n=21 in each group) performed MBW and spirometry before and after exercise and again after salbutamol, symptom data was collected from asthmatic children. Baseline LCI was abnormal in the asthmatic group who had severe exercise induced bronchospasm during testing. (5) Asthmatic children admitted to hospital due to exacerbation performed MBW and spirometry. Mean (SD) LCI was abnormally high at 8.5 (1.7) in the nine patients recruited and returned to normal 6.7 (0.6) in three patients who attended follow up. I have presented evidence that LCI is repeatable and sensitive to early disease in CF and asthma. I have described for the first time the effects of exercise and exacerbation on MBW indices in asthmatic children. MBW is potentially a very useful tool in paediatrics; standardisation of testing and equipment may enable clinical use

Bioactive Indanes: Development and Validation of an LC-MS/MS Bioanalytical Method for the Determination of PH46A, a New Potential Anti-inflammatory Agent, in Dog and Rat Plasma and its Application to a Pharmacokinetic Study in Dog

A new chemical entity, which is a chiral indane dimer, PH46A, has been developed by our research group. As a clinical candidate. PH46A has recently completed Phase I clinical studies in man. Previously, during its pre-clinical development, in in vivo pre-clinical studies PH46A showed potent anti-inflammatory properties, which can be targeted at a range of diseases, including inflammatory bowel disease (IBD). To support the pre-clinical development of this drug candidate, we developed a LC MS/MS method for determining PH46 (the acid form of PH46A salt) in both dog and rat plasma using Compound 1 as internal standard (IS). Those species were selected for safety pharmacology and toxicology, as well as pharmacokinetics studies. Themethod was validatedover the range 10−10000 ng/mL for bothmatrices andthe linearity, accuracy, precision and specificity over this range were demonstrated to be acceptable. No significant matrix effects or carryover were observed for both PH46 and IS and recovery was consistent. PH46 was found to be stable in both dog and rat plasma under the test conditions, such as at room temperature for \u3e24 h, through 3 freeze/thaw cycles, and at -20 ◦C for \u3e1 month. PH46 and IS in dog and rat plasma extracts were also found to be stable in the autosampler against fresh standard extracts on re-injection after 143.5 h and 243.5 h, respectively at 4 ◦C. 10- and 100-fold dilutions with control matrix were found not to affect the performance of the assay. This method was successfully applied to a pharmacokinetic study in the dog. With the exception of one dog, 003 M, oral administration of PH46A in gelatine capsules was well tolerated at a dose level of 100 mg/kg. The highest Cmax was observed in animal 003 M. The rapid absorption and high plasma concentration observed for animal 003 M compared to the data for animals 001 M and 002 M may account for the sickness observed in this animal; however, the reasons for this have not been investigate

Bioactive Indanes: Comparative In Vitro Metabolism Study of PH46A, a New Potential Anti-inflammatory Agent and biosynthesis of its primary metabolite PH132

PH46A is the lead of a new class of bioactive indanes with potential for the treatment of inflammatory bowel disease. A qualitative in vitro metabolism profile of PH46A was investigated in preclinical studies, and the rate of its metabolism in cryopreserved hepatocytes prepared from male Sprague Dawley rat, Beagle dog, Cynomolgus monkey and pooled mixed gender human was compared by LC-MS. The clearance order of PH46A was determined to be rat\u3edog\u3emonkey\u3ehuman. The species tested which exhibited the closest clearance values to the human was monkey. Following incubation of PH46A with cryopreserved hepatocytes, 5 metabolites were identified, including M1 (keto-PH46), M2 (PH46-OH, PH132), M3 (PH46-diOH), M4 (keto-glucuronide-PH46) and M5 (glucuronide conjugate-PH46). It was found that the human metabolites M2 and M5 were also present in rat, dog and monkey, while M1 was present in all species except monkey. M2 was detected in dog and monkey by LC1 conditions, but only in dog by LC2. Therefore, the metabolism in rat was most similar to human, in terms of the metabolites observed, but all putative human metabolites were present in rat and dog. We further explored the characterization of key metabolite M2 (PH46-OH). Identical PH46-OH was obtained via a bio-catalytic oxidation method from PH46 using rat liver microsomes (RLM) and the human liver P450s (Cyp 2D6, Cyp 2C19 and Cyp 4A11) following screening of selectAZyme panels of microbial P450s, recombinant human liver P450s and different microsomes. RLM was used in scale up production and PH132 was isolated and characterized as 4-(((1’S,2’S)-1’,6-dihydroxy-1’,3’-dihydro- 1H,2’H-[2,2’-biinden]-2’-yl)methyl) benzoic acid via LC-MS/MS, NMR and HRMS. The site of hydroxylation on the biindane scaffold was unexpected. The outcomes of these studies have provided valuable information for future pharmacokinetic and in vivo toxicological investigations