66 results on '"Kevin McDonnell"'
Search Results
2. O06: Penetrance and prevalence of CDKN2A pathogenic variants in a large institutional cohort: Scrutinizing the common p.Ile49Thr variant
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Lauren Gima, Christina Fujii, Michael Restrepo, Christina Rybak, Elise Sobotka, Elyssa Zukin, Lawrence Shaktah, Joanne Jeter, Kevin McDonnell, Wai Park, Gregory Idos, Heather Hampel, and Stacy Gray
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Genetics ,QH426-470 ,Medicine - Published
- 2024
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3. P077: Have we considered mosaicism? A nearly missed molecular diagnosis of von Hippel-Lindau
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Wai Park, Elyssa Zukin, Rachelle Manookian, Kevin McDonnell, Szabolcs Szelinger, Ali Zhumkhawala, and Stacy Gray
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Genetics ,QH426-470 ,Medicine - Published
- 2024
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4. P083: Prevalence and penetrance of LZTR1 pathogenic variants: To screen or not to screen?
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Susan Shehayeb, Hunaydah Elfarawi, Kaila Wilson, Wai Park, Anuja Chitre, Lawrence Shaktah, Duveen Sturgeon, Kevin McDonnell, Heather Hampel, Alexandra Capasso, and Stacy Gray
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Genetics ,QH426-470 ,Medicine - Published
- 2024
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5. 1124 Discovery and evaluation of bicyclic peptides as modulators of pattern recognition receptors
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Heather Scott, Katie Hill, Liuhong Chen, Kevin McDonnell, Philip Brandish, Nicholas Keen, Rachel Dodds, Laura L Goodfield, Robert P Hammer, Winston Lu, Tamera Ashworth, Hannah S Gardner, Luca Mascheroni, Tazmin Martin, Matthieu Masureel, Sandra Uhlenbroich, Marta Amaral, Julia Kristenson, and Gemma E Mudd
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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6. Critical evaluation of the use of artificial data for machine learning based de novo peptide identification
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Kevin McDonnell, Enda Howley, and Florence Abram
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de novo ,Artificial data ,Synthetic data ,Peptide sequencing ,Noise ,Biotechnology ,TP248.13-248.65 - Abstract
Proteins are essential components of all living cells and so the study of their in situ expression, proteomics, has wide reaching applications. Peptide identification in proteomics typically relies on matching high resolution tandem mass spectra to a protein database but can also be performed de novo. While artificial spectra have been successfully incorporated into database search pipelines to increase peptide identification rates, little work has been done to investigate the utility of artificial spectra in the context of de novo peptide identification. Here, we perform a critical analysis of the use of artificial data for the training and evaluation of de novo peptide identification algorithms. First, we classify the different fragment ion types present in real spectra and then estimate the number of spurious matches using random peptides. We then categorise the different types of noise present in real spectra. Finally, we transfer this knowledge to artificial data and test the performance of a state-of-the-art de novo peptide identification algorithm trained using artificial spectra with and without relevant noise addition. Noise supplementation increased artificial training data performance from 30% to 77% of real training data peptide recall. While real data performance was not fully replicated, this work provides the first steps towards an artificial spectrum framework for the training and evaluation of de novo peptide identification algorithms. Further enhanced artificial spectra may allow for more in depth analysis of de novo algorithms as well as alleviating the reliance on database searches for training data.
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- 2023
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7. Assessment of the Potential to Use the Expelled Heat Energy from a Typical Data Centre in Ireland for Alternative Farming Methods
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Peter L. Borland, Kevin McDonnell, and Mary Harty
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data centre ,vertical farming ,energy-saving ,sustainability ,emission reductions ,waste heat energy ,Technology - Abstract
Data centres, though a necessary part of modern society, are being stigmatised for consuming vast amounts of electricity for their operational and cooling needs. Due to Ireland’s reliance on fossil fuels to meet the increased energy demand of data centres, the data centres are contributing significantly to Ireland’s total carbon emissions. As much of this energy is expelled from data centres as waste heat energy, the potential for recycling some of this wasted heat energy was explored using environmentally friendly systems from recent publications. The recovered waste heat energy was applied in a vertical farming system, and the benefits of this waste heat to the vertical farm were analysed and quantified in two scenarios. Using conservative estimates, it was predicted that each vertical farm could be between 5–23% the size of the data centre and produce enough food to feed between 14–61 adults their daily calorie needs, and between 13–58 people their daily fresh produce requirements, depending on the scenario applied. For a more accurate prediction, each vertical farm would have to be assessed on a case-by-case basis, as there is no current research in this area. However, there was not enough data available on Irish data centres to perform these calculations.
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- 2023
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8. The impact of noise and missing fragmentation cleavages on de novo peptide identification algorithms
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Kevin McDonnell, Enda Howley, and Florence Abram
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De novo peptide sequencing ,Machine learning ,Peptide identification ,Noise ,Fragmentation cleavage sites ,Peptide fragmentation ,Biotechnology ,TP248.13-248.65 - Abstract
Proteomics aims to characterise system-wide protein expression and typically relies on mass-spectrometry and peptide fragmentation, followed by a database search for protein identification. It has wide ranging applications from clinical to environmental settings and virtually impacts on every area of biology. In that context, de novo peptide sequencing is becoming increasingly popular. Historically its performance lagged behind database search methods but with the integration of machine learning, this field of research is gaining momentum. To enable de novo peptide sequencing to realise its full potential, it is critical to explore the mass spectrometry data underpinning peptide identification. In this research we investigate the characteristics of tandem mass spectra using 8 published datasets. We then evaluate two state of the art de novo peptide sequencing algorithms, Novor and DeepNovo, with a particular focus on their performance with regard to missing fragmentation cleavage sites and noise. DeepNovo was found to perform better than Novor overall. However, Novor recalled more correct amino acids when 6 or more cleavage sites were missing. Furthermore, less than 11% of each algorithms’ correct peptide predictions emanate from data with more than one missing cleavage site, highlighting the issues missing cleavages pose. We further investigate how the algorithms manage to correctly identify peptides with many of these missing fragmentation cleavages. We show how noise negatively impacts the performance of both algorithms, when high intensity peaks are considered. Finally, we provide recommendations regarding further algorithms’ improvements and offer potential avenues to overcome current inherent data limitations.
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- 2022
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9. On the road safety benefits of advanced driver assistance systems in different driving contexts
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Leandro Masello, German Castignani, Barry Sheehan, Finbarr Murphy, and Kevin McDonnell
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Accident reduction ,Advanced driver assistance systems ,Analytic Hierarchy Process ,Connected and automated vehicles ,Road safety reports ,Safety effectiveness ,Transportation and communications ,HE1-9990 - Abstract
Advanced Driver Assistance Systems (ADAS) have introduced several benefits in the vehicular industry, and their proliferation presents potential opportunities to decrease road accidents. The reasons are mainly attributed to the enhanced perception of the driving environment and reduced human errors. However, as environmental and infrastructural conditions influence the performance of ADAS, the estimation of accident reductions varies across geographical regions. This study presents an interdisciplinary methodology that integrates the literature on advanced driving technologies and road safety to quantify the expected impact of ADAS on accident reduction across combinations of road types, lighting, and weather conditions. The paper investigates the safety effectiveness of ADAS and the distribution of frequency and severity of road accidents across 18 driving contexts and eight accident types. Using road safety reports from the United Kingdom (UK), it is found that a high concentration of accidents (77%) occurs within a small subset of contextual conditions (4 out of 18) and that the most severe accidents happen in dark conditions on rural roads or motorways. The results of the safety effectiveness analysis show that a full deployment of the six most common ADAS would reduce the road accident frequency in the UK by 23.8%, representing an annual decrease of 18,925 accidents. The results also show that the most frequent accident contexts, urban-clear-daylight and rural-clear-daylight, can be reduced by 29%, avoiding 7,020 and 3,472 accidents, respectively. Automatic Emergency Braking (AEB) is the most impactful technology, reducing three out of the four most frequent accident categories – intersection (by 28%), rear-end (by 27.7%), and pedestrian accidents (by 28.4%). This study helps prioritise resources in ADAS research and development focusing on the most relevant contexts to reduce the frequency and severity of road accidents. Furthermore, the identified contextual accident hotspots can assist road safety stakeholders in risk mitigation programs.
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- 2022
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10. BT7480, a novel fully synthetic Bicycle tumor-targeted immune cell agonist™ (Bicycle TICA™) induces tumor localized CD137 agonism
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Jun Ma, Kristen Hurov, Johanna lahdenranta, Punit Upadhyaya, Elizabeth Repash, Julia Kristensson, Eric Haines, Kevin McDonnell, Philip Brandish, Nicholas Keen, Fanglei You, Mike Kelly, Heather Cohen, Drasti Kanakia, Carly Campbell, David Witty, Stephen Blakemore, and Phil Jeffrey
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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11. 888 An integrative approach to optimize a synthetic EphA2/CD137 agonist: balancing potency, physiochemical properties, and pharmacokinetics to achieve robust anti-tumor activity
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Kristen Hurov, Johanna lahdenranta, Gemma Mudd, Punit Upadhyaya, Elizabeth Repash, Julia Kristensson, Kevin McDonnell, Philip Brandish, Nicholas Keen, and Phil Jeffrey
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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12. Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist
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Sailaja Battula, Kristen Hurov, Johanna lahdenranta, Gemma Mudd, Punit Upadhyaya, Elizabeth Repash, Julia Kristensson, Marianna Kleyman, Jessica Kublin, Liuhong Chen, Eric Haines, Kevin McDonnell, Philip Brandish, Nicholas Keen, Rachel Dods, Rachid Lani, Katerine Van Rietschoten, Tom Stephen, and Fanglei You
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background In contrast to immune checkpoint inhibitors, the use of antibodies as agonists of immune costimulatory receptors as cancer therapeutics has largely failed. We sought to address this problem using a new class of modular synthetic drugs, termed tumor-targeted immune cell agonists (TICAs), based on constrained bicyclic peptides (Bicycles).Methods Phage libraries displaying Bicycles were panned for binders against tumor necrosis factor (TNF) superfamily receptors CD137 and OX40, and tumor antigens EphA2, Nectin-4 and programmed death ligand 1. The CD137 and OX40 Bicycles were chemically conjugated to tumor antigen Bicycles with different linkers and stoichiometric ratios of binders to obtain a library of low molecular weight TICAs (MW
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- 2021
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13. 700 EphA2/CD137 Bicycle tumor-targeted immune cell agonists (TICAsTM) induce tumor regressions, immunogenic memory, and reprogramming of the tumor immune microenvironment
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Jun Ma, Sailaja Battula, Kristen Hurov, Johanna lahdenranta, Gemma Mudd, Punit Upadhyaya, Elizabeth Repash, Julia Kristensson, Marianna Kleyman, Jessica Kublin, Liuhong Chen, Eric Haines, Kevin McDonnell, Philip Brandish, and Nicholas Keen
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
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14. Regulatory and Technical Constraints: An Overview of the Technical Possibilities and Regulatory Limitations of Vehicle Telematic Data
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Kevin McDonnell, Finbarr Murphy, Barry Sheehan, Leandro Masello, German Castignani, and Cian Ryan
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connected and autonomous vehicles ,intelligent transport systems ,telematics ,regulation ,Chemical technology ,TP1-1185 - Abstract
A telematics device is a vehicle instrument that comes preinstalled by the vehicle manufacturer or can be added later. The device records information about driving behavior, including speed, acceleration, and turning force. When connected to vehicle computers, the device can also provide additional information regarding the mechanical usage and condition of the vehicle. All of this information can be transmitted to a central database via mobile networks. The information provided has led to new services such as Usage Based Insurance (UBI). A range of consultants, industry commentators and academics have produced an abundance of projections on how telematics information will allow the introduction of services from personalized insurance, bespoke entertainment and advertise and vehicle energy optimization, particularly for Electric Vehicles (EVs). In this paper we examine these potential services against a backdrop of nascent regulatory limitations and against the technical capacity of the devices. Using a case study approach, we examine three applications that can use telematics information. We find that the expectations of service providers will be significantly tempered by regulatory and technical hurdles. In our discussion we detail these limitations and suggest a more realistic rollout of ancillary services.
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- 2021
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15. Feasibility Study of Carbon Dioxide Plume Geothermal Systems in Germany−Utilising Carbon Dioxide for Energy
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Kevin McDonnell, Levente Molnár, Mary Harty, and Fionnuala Murphy
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geothermal ,carbon dioxide ,sequestration ,Germany ,coal ,carbon capture and utilization ,Technology - Abstract
To manage greenhouse gas emissions, directives on renewable energy usage have been developed by the European Commission with the objective to reduce overall emissions by 40% by 2030 which presents a significant potential for renewable energy sources. At the same time, it is a challenge for these energy technologies which can only be solved by integrated solutions. Carbon capture and storage combined with geothermal energy could serve as a novel approach to reduce CO2 emissions and at the same time facilitate some of the negative impacts associated with fossil fuel-based power plants. This study focuses on the technical and economic feasibility of combining these technologies based on a published model, data and market research. In the European Union, Germany is the most energy intensive country, and it also has an untapped potential for geothermal energy in the northern as well as the western regions. The CO2 plume geothermal system using supercritical carbon dioxide as the working fluid can be utilized in natural high porosity (10–20%) and permeability (2.5 × 10−14–8.4 × 10−16 m2) reservoirs with temperatures as low as 65.8 °C. The feasibility of the project was assessed based on market conditions and policy support in Germany as well as the geologic background of sandstone reservoirs near industrialized areas (Dortmund, Frankfurt) and the possibility of carbon capture integration and CO2 injection. The levelized cost of electricity for a base case results in € 0.060/kWh. Optimal system type was assessed in a system optimization model. The project has a potential to supply 6600/12000 households with clean energy (electricity/heat) and sequester carbon dioxide at the same time. A trading scheme for carbon dioxide further expands potential opportunities.
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- 2020
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16. Analysing Performance Characteristics of Biomass Haulage in Ireland for Bioenergy Markets with GPS, GIS and Fuel Diagnostic Tools
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Amanda Sosa, Kevin McDonnell, and Ger Devlin
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transportation ,geographic information systems (GIS) ,Network Analyst (NA) ,biomass ,bioenergy markets ,optimal routes ,fleet management ,Ireland ,Technology - Abstract
In Ireland, truck transport by road dominates and will remain the main transportation mode of biomass. Cost efficiency and flexibility of forest transport can be typically improved by optimising routes. It is important to know every process and attributes within the workflow of roundwood transport. This study aimed to analyse characteristics of timber trucking in Ireland, and to estimate the least-cost route for the distribution of biomass with the use of geographic information systems (GIS). Firstly, a tracking system that recorded the truck’s movements and fuel consumption was installed. A total of 152 trips were recorded, routes were chosen by the truck driver. The recorded information was used to analyse the distances and times travelled loaded and unloaded per road class, breaks, loading and unloading times as well as fuel consumption. Secondly, the routes taken by the truck where compared with routes created using Network Analyst (NA), an extension of ArcGIS. Four scenarios based on route selection criteria were selected: shortest distance (S1), shorted time (S2), and prioritising high-class roads with shortest distance (S3) and time (S4). Results from the analysis of the tracking system data showed that driving both loaded and unloaded occupied on average 69% of the driver’s working shift; with an average time driving loaded of 49%. The travel distance per trip varied from 112 km and 197 km, with the truck driver using mostly national and regional roads. An average 2% of the total distance and 11% of the total time was spent driving on forest roads. In general, the truck’s speed recorded on the different road classes was on average 30% lower than the legal maximum speed. The average fuel consumption was 0.64 L/km. In terms of the route comparison, the driving directions from the truck routes coincided with 77% of the directions of the routes based on shortest driving time (S2 and S4). All the routes chosen by the driver had 22% longer distance than the routes in S1 (shortest distance). The routes selected based on shortest distance (S1 and S3) had the longest travelling time, approximately 19% more than the ones taken by the truck and 30% more than S2 and S4. The average running cost for the truck was 0.83 €/km. Choosing the shortest distance routes (S1 and S3) not only implies reducing travelling costs but also a reduction of CO2 emissions by 12% in comparison to routes in S2 and S4. However, when selecting the routes, travel time can be a much more crucial parameter to analyse rather than distance in terms of transportation costs. Choosing the routes generated in scenario S2 over S1 implied an increase in distance by 12% but a decrease in time of 30%. Less driving time translates into better driving conditions across higher classes or roads; less wear and tear of trucks; and lesser fuel used. It also complies with local authorities preferences of having timber trucks move on higher road types in order to minimise the expenses associated with road maintenance.
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- 2015
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17. Novel Approaches to Optimise Early Growth in Willow Crops
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Isabella Donnelly, Kevin McDonnell, and John Finnan
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willow ,early growth ,coppicing ,stem orientation ,pre-soaking ,Agriculture (General) ,S1-972 - Abstract
Willow is a fast growing, high yielding biomass crop that can help reduce reliance on fossil fuels. However, long establishment times to get to profitability and sustainable yield may deter interest in planting the crop. A number of different approaches were investigated to optimise and accelerate early growth. These approaches were water immersion, plastic application, altering stem orientation at planting, altering coppicing timings and applying growth hormone. Glasshouse and field trials were used to test the different approaches. In this work, planting material was soaked for a varying number of days and plastic was applied or not applied in field trials. In the planting orientation approach, stems were planted diagonally or vertically with half of the planting material above the ground level or horizontally below ground level. Additionally, willow crops were coppiced at different times throughout their first growing season and a growth hormone trial was also incorporated in this work. Water soaking, plastic application, coppicing during the growing season or hormone application did not improve early growth or yield. However, early growth and yield were increased by manipulating the planting orientation of willow stems. Planting orientation treatments in which part of the stem was left above the ground increased early growth and yield significantly compared to the control without requiring extra inputs at planting. The beneficial effects of coppicing can be achieved by manipulating the planting procedure so that the first year’s growth is not disregarded.
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- 2019
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18. Biofuel Production in Ireland—An Approach to 2020 Targets with a Focus on Algal Biomass
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Fionnuala Murphy, Ger Devlin, Rory Deverell, and Kevin McDonnell
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biodiesel ,bioethanol ,microalgae ,macroalgae ,indigenous production ,Ireland ,Technology - Abstract
Under the Biofuels Obligation Scheme in Ireland, the biofuels penetration rate target for 2013 was set at 6% by volume from a previous 4% from 2010. In 2012 the fuel blend reached 3%, with approximately 70 million L of biodiesel and 56 million L of ethanol blended with diesel and gasoline, respectively. Up to and including April 2013, the current blend rate in Ireland for biodiesel was 2.3% and for bioethanol was 3.7% which equates to approximately 37.5 million L of biofuel for the first four months of 2013. The target of 10% by 2020 remains, which equates to approximately 420 million L yr−1. Achieving the biofuels target would require 345 ktoe by 2020 (14,400 TJ). Utilizing the indigenous biofuels in Ireland such as tallow, used cooking oil and oil seed rape leaves a shortfall of approximately 12,000 TJ or 350 million L (achieving only 17% of the 10% target) that must be either be imported or met by other renewables. Other solutions seem to suggest that microalgae (for biodiesel) and macroalgae (for bioethanol) could meet this shortfall for indigenous Irish production. This paper aims to review the characteristics of algae for biofuel production based on oil yields, cultivation, harvesting, processing and finally in terms of the European Union (EU) biofuels sustainability criteria, where, up to 2017, a 35% greenhouse gas (GHG) emissions reduction is required compared to fossil fuels. From 2017 onwards, a 50% GHG reduction is required for existing installations and from 2018, a 60% reduction for new installations is required.
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- 2013
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19. Co-Fuelling of Peat with Meat and Bone Meal in a Pilot Scale Bubbling Bed Reactor
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Markku Orjala, Colette C. Fagan, Kevin McDonnell, and Enda J. Cummins
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bubbling bed reactor ,meat & bone meal ,co-combustion ,flue gas emissions ,peat ,Technology - Abstract
Co-combustion performance trials of Meat and Bone Meal (MBM) and peat were conducted using a bubbling fluidized bed (BFB) reactor. In the combustion performance trials the effects of the co-combustion of MBM and peat on flue gas emissions, bed fluidization, ash agglomeration tendency in the bed and the composition and quality of the ash were studied. MBM was mixed with peat at 6 levels between 15% and 100%. Emissions were predominantly below regulatory limits. CO concentrations in the flue gas only exceeded the 100 mg/m3 limit upon combustion of pure MBM. SO2 emissions were found to be over the limit of 50 mg/m3, while in all trials NOx emissions were below the limit of 300 mg/m3. The HCl content of the flue gases was found to vary near the limit of 30 mg/m3. VOCs however were within their limits. The problem of bed agglomeration was avoided when the bed temperature was about 850 °C and only 20% MBM was co-combusted. This study indicates that a pilot scale BFB reactor can, under optimum conditions, be operated within emission limits when MBM is used as a co-fuel with peat. This can provide a basis for further scale-up development work in industrial scale BFB applications.
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- 2010
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20. Potential Bioethanol Feedstock Availability Around Nine Locations in the Republic of Ireland
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Rory Deverell, Kevin McDonnell, and Ger Devlin
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GIS ,Supply strategy ,Land-use ,Ireland ,Wheat ,Sugarbeet ,Straw ,Bioethanol ,Technology - Abstract
The Republic of Ireland, like many other countries is trying to diversify energy sources to counteract environmental, political and social concerns. Bioethanol from domestically grown agricultural crops is an indigenously produced alternative fuel that can potentially go towards meeting the goal of diversified energy supply. The Republic of Ireland’s distribution of existing soils and agricultural land-uses limit arable crop land to around 10% of total agricultural area. Demand for land to produce arable crops is expected to decrease, which could open the opportunity for bioethanol production. Bioethanol production plants are required to be of a sufficient scale in order to compete economically with other fuel sources, it is important therefore to determine if enough land exists around potential ethanol plant locations to meet the potential demands for feedstock. This study determines, through the use of a developed GIS based model, the potential quantities of feedstock that is available in the hinterlands of nine locations in the Republic of Ireland. The results indicate that three locations can meet all its feedstock demands using indigenously grown sugarbeet, while only one location can meet its demands using a combination of indigenous wheat and straw as the two locally sourced feedstocks.
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- 2009
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21. Discovery of novel human breast cancer microRNAs from deep sequencing data by analysis of pri-microRNA secondary structures.
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Seongho Ryu, Natasha Joshi, Kevin McDonnell, Jongchan Woo, Hyejin Choi, Dingcheng Gao, William R McCombie, and Vivek Mittal
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Medicine ,Science - Abstract
MicroRNAs (miRNAs) are key regulators of gene expression and contribute to a variety of biological processes. Abnormal miRNA expression has been reported in various diseases including pathophysiology of breast cancer, where they regulate protumorigenic processes including vascular invasiveness, estrogen receptor status, chemotherapy resistance, invasion and metastasis. The miRBase sequence database, a public repository for newly discovered miRNAs, has grown rapidly with approximately >10,000 entries to date. Despite this rapid growth, many miRNAs have not yet been validated, and several others are yet to be identified. A lack of a full complement of miRNAs has imposed limitations on recognizing their important roles in cancer, including breast cancer. Using deep sequencing technology, we have identified 189 candidate novel microRNAs in human breast cancer cell lines with diverse tumorigenic potential. We further show that analysis of 500-nucleotide pri-microRNA secondary structure constitutes a reliable method to predict bona fide miRNAs as judged by experimental validation. Candidate novel breast cancer miRNAs with stem lengths of greater than 30 bp resulted in the generation of precursor and mature sequences in vivo. On the other hand, candidates with stem length less than 30 bp were less efficient in producing mature miRNA. This approach may be used to predict which candidate novel miRNA would qualify as bona fide miRNAs from deep sequencing data with approximately 90% accuracy.
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- 2011
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22. Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
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Ceres Fernandez-Rozadilla, Maria Timofeeva, Zhishan Chen, Philip Law, Minta Thomas, Stephanie Schmit, Virginia Díez-Obrero, Li Hsu, Juan Fernandez-Tajes, Claire Palles, Kitty Sherwood, Sarah Briggs, Victoria Svinti, Kevin Donnelly, Susan Farrington, James Blackmur, Peter Vaughan-Shaw, Xiao-ou Shu, Jirong Long, Qiuyin Cai, Xingyi Guo, Yingchang Lu, Peter Broderick, James Studd, Jeroen Huyghe, Tabitha Harrison, David Conti, Christopher Dampier, Mathew Devall, Fredrick Schumacher, Marilena Melas, Gad Rennert, Mireia Obón-Santacana, Vicente Martín-Sánchez, Ferran Moratalla-Navarro, Jae Hwan Oh, Jeongseon Kim, Sun Ha Jee, Keum Ji Jung, Sun-Seog Kweon, Min-Ho Shin, Aesun Shin, Yoon-Ok Ahn, Dong-Hyun Kim, Isao Oze, Wanqing Wen, Keitaro Matsuo, Koichi Matsuda, Chizu Tanikawa, Zefang Ren, Yu-Tang Gao, Wei-Hua Jia, John Hopper, Mark Jenkins, Aung Ko Win, Rish Pai, Jane Figueiredo, Robert Haile, Steven Gallinger, Michael Woods, Polly Newcomb, David Duggan, Jeremy Cheadle, Richard Kaplan, Timothy Maughan, Rachel Kerr, David Kerr, Iva Kirac, Jan Böhm, Lukka-Pekka Mecklin, Pekka Jousilahti, Paul Knekt, Lauri Aaltonen, Harri Rissanen, Eero Pukkala, Johan Eriksson, Tatiana Cajuso, Ulrika Hänninen, Johanna Kondelin, Kimmo Palin, Tomas Tanskanen, Laura Renkonen-Sinisalo, Brent Zanke, Satu Männistö, Demetrius Albanes, Stephanie Weinstein, Edward Ruiz-Narvaez, Julie Palmer, Daniel Buchanan, Elizabeth Platz, Kala Visvanathan, Cornelia Ulrich, Erin Siegel, Stefanie Brezina, Andrea Gsur, Peter Campbell, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Martha Slattery, John Potter, Konstantinos Tsilidis, Matthias Schulze, Marc Gunter, Neil Murphy, Antoni Castells, Sergi Castellví-Bel, Leticia Moreira, Volker Arndt, Anna Shcherbina, Mariana Stern, Bens Pardamean, Timothy Bishop, Graham Giles, Melissa Southey, Gregory Idos, Kevin McDonnell, Zomoroda Abu-Ful, Joel Greenson, Katerina Shulman, Flavio Lejbkowicz, Kenneth Offit, Yu-Ru Su, Robert Steinfelder, Temitope Keku, Bethany van Guelpen, Thomas Hudson, Heather Hampel, Rachel Pearlman, Sonja Berndt, Richard Hayes, Marie Elena Martinez, Sushma Thomas, Douglas Corley, Paul Pharoah, Susanna Larsson, Yun Yen, Heinz-Josef Lenz, Emily White, Li Li, Kimberly Doheny, Elizabeth Pugh, Tameka Shelford, Andrew Chan, Marcia Cruz-Correa, Annika Lindblom, David Hunter, Amit Joshi, Clemens Schafmayer, Peter Scacheri, Anshul Kundaje, Deborah Nickerson, Robert Schoen, Jochen Hampe, Zsofia Stadler, Pavel Vodicka, Ludmila Vodickova, Veronika Vymetalkova, Nickolas Papadopoulos, Chistopher Edlund, William Gauderman, Duncan Thomas, David Shibata, Amanda Toland, Sanford Markowitz, Andre Kim, Stephen Chanock, Franzel van Duijnhoven, Edith Feskens, Lori Sakoda, Manuela Gago-Dominguez, Alicja Wolk, Alessio Naccarati, Barbara Pardini, Liesel FitzGerald, Soo Chin Lee, Shuji Ogino, Stephanie Bien, Charles Kooperberg, Christopher Li, Yi Lin, Ross Prentice, Conghui Qu, Stéphane Bézieau, Catherine Tangen, Elaine Mardis, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Christopher Haiman, Loic Le Marchand, Anna Wu, Chenxu Qu, Caroline McNeil, Gerhard Coetzee, Caroline Hayward, Ian Deary, Sarah Harris, Evropi Theodoratou, Stuart Reid, Marion Walker, Li Yin Ooi, Victor Moreno, Graham Casey, Stephen Gruber, Ian Tomlinson, Wei Zheng, Malcolm Dunlop, Richard Houlston, and Ulrike Peters
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Global Nutrition ,Wereldvoeding ,Nutrition and Disease ,Voeding en Ziekte ,Genetics ,Life Science ,Article ,VLAG - Abstract
Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and East Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions, and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Cross-tissue analyses indicated that over a third of effector genes most likely act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis, and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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- 2023
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23. Resource recovery from the anaerobic digestion of food waste is underpinned by cross-kingdom microbial activities
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Sally L. Shirran, Camilla Thorn, Florence Abram, Corine Nzeteu, Vincent O'Flaherty, Kevin McDonnell, Aoife Joyce, University of St Andrews. School of Biology, and University of St Andrews. Biomedical Sciences Research Complex
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Acidogenesis ,Environmental Engineering ,Firmicutes ,Population ,Bioengineering ,Resource recovery from waste ,Metaproteomics ,Anaerobic digestion ,16S rRNA profiling ,Food science ,education ,Waste Management and Disposal ,Resource recovery ,education.field_of_study ,GE ,biology ,Renewable Energy, Sustainability and the Environment ,DAS ,QR Microbiology ,biology.organism_classification ,QR ,Food waste ,Acetogenesis ,Environmental science ,Proteobacteria ,GE Environmental Sciences - Abstract
This work was supported by the Earth and Natural Sciences (ENS) Doctoral Studies Programme, funded by the Higher Education Authority (HEA) of Ireland through the Programme for Research at Third Level Institutions, Cycle 5 (PRTLI-5), co-funded by the European Regional Development Fund (ERDF). As the human population grows on the planet so does the generation of waste and particularly that of food waste. In order to tackle the world sustainability crisis, efforts to recover products from waste are critical. Here, we anaerobically recovered volatile fatty acids (VFAs) from food waste and analysed the microbial populations underpinning the process. An increased contribution of fungi relative to bacteria was observed throughout the reactor operation, with both kingdoms implicated into the main three steps of anaerobic digestion occurring within our systems: hydrolysis, acidogenesis and acetogenesis. Overall, Ascomycota, Proteobacteria and Firmicutes were found to drive the anaerobic digestion of food waste, with butyrate as the most abundant VFA likely produced by Clostridium using lactate as a precursor. Taken together we demonstrate that the generation of products of added-value from food waste results from cross-kingdoms microbial activities implicating fungi and bacteria. Publisher PDF
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- 2021
24. The effect of tillage depth and traffic management on soil properties and root development during two growth stages of winter wheat (Triticum aestivum L.)
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Saoirse R. Tracy, Mary Harty, David Hobson, and Kevin McDonnell
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Tillage ,Soil management ,No-till farming ,Soil structure ,Agronomy ,Crop yield ,Soil water ,Environmental science ,Soil Science ,Root system ,Bulk density - Abstract
The management of agricultural soils during crop establishment can affect root development due to changes in the soil structure. This paper assesses the influence of tillage depth (250 mm, 100 mm, and zero tillage) and traffic management (conventional tyre pressure, low tyre pressure, and no traffic) on wheat root system architecture during winter wheat (Triticum aestivum L.) tillering and flowering growth stages (GS) at a long-term tillage trial site. The study revealed that zero-tillage systems increased crop yield through significantly greater root biomass (P<0.001), root length density, and deeper seminal rooting analysed using X-ray computed tomography (CT) (P<0.001) compared with trafficked treatments. In general, conventional-pressure traffic had a significant negative influence on the crop yield (P<0.01), root development (0.001), bulk density (P<0.05), and total soil porosity (P<0.05) of deep- and shallow-tillage conventional-pressure systems compared with no-traffic zero- and deep-tillage systems. Visual improvements in soil structure under zero-tillage conditions may have improved crop rooting in zero-tillage treatments through vertical pore fissures (biopores), enhancing water uptake during the crop flowering period. This study highlights the increasing implications of soil structural damage on root system architecture created by machinery traffic in crop production. Although the tillage method was less important, the constricted root systems were more pronounced in conventional-pressure shallow-tillage and deep-tillage systems, emphasizing the importance of using controlled-traffic farming methods to improve soil management and reduce the trafficked areas of agricultural fields.
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- 2021
25. Novel Common Genetic Susceptibility Loci for Colorectal Cancer
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Katja Butterbach, Julyann Pérez-Mayoral, Douglas F. Easton, Stefanie Brezina, Ben Zhang, Frank J. Manion, Hansong Wang, Sanford D. Markowitz, Liesel M. FitzGerald, Sun Ha Jee, Michelle Cotterchio, Daniel D. Buchanan, Timothy R. Church, Wolfgang Lieb, Xiao-Ou Shu, John L. Hopper, Stephanie A. Bien, Manuela Gago-Dominguez, Jian Gong, Laurence N. Kolonel, Graham G. Giles, Leon Raskin, Yingchang Lu, Kristen Anton, Charles S. Fuchs, Fränzel J.B. van Duijnhoven, Hermann Brenner, Yi Lin, Clicerio Gonzalez-Villalpando, Yong-Bing Xiang, Aaron K. Aragaki, Daniela Seminara, Stephanie M. Gogarten, Gad Rennert, Jose E. Castelao, Rocky Fischer, Antonio J. Molina, Jarmo Virtamo, Tabitha A. Harrison, Volker Arndt, Lee Soo Chin, Michael Hoffmeister, Mark A. Jenkins, Shu Chen Huang, Chris S. Carlson, Stéphane Bézieau, Rebecca D. Jackson, Bhramar Mukherjee, Darin Taverna, Bridget M. Riggs, Christopher K. Edlund, Christopher A. Haiman, Melissa C. Southey, Anna H. Wu, Marilena Melas, Antonia Trichopoulou, Hedy S. Rennert, Gianluca Severi, Stephen B. Gruber, Noralane M. Lindor, Gerhard A. Coetzee, Richard B. Hayes, Sarah J. Plummer, Keitaro Matsuo, Mathieu Lemire, Philipp Hofer, Neil Murphy, José María Huerta, Paul D.P. Pharoah, Erin M. Siegel, Sébastien Küry, Thomas J. Hudson, Annika Lindblom, Marcia Cruz Correa, Michael O. Woods, Sophia Harlid, Tilman Kuehn, David Shibata, Christopher I. Li, Stephen N. Thibodeau, Stephen J. Chanock, Jochen Hampe, Flavio Lejbkowicz, Jeroen R. Huyghe, Suminori Kono, Jenny Chang-Claude, Aung Ko Win, Brent W. Zanke, Alicja Wolk, David V. Conti, Elena M. Gonzalez-Villalpando, Christopher I. Amos, Shuo Jiao, Domenico Palli, Vicente Martín, Jesus P. Paredes Cotoré, Stephanie J. Weinstein, Andrea Gsur, William M. Grady, Koichi Matsuda, Loic Le Marchand, Hanane Omichessan, Marc J. Gunter, Graham Casey, Li Li, Zsofia K. Stadler, Eric J. Jacobs, Kevin McDonnell, Dallas R. English, Demetrius Albanes, Amit Joshi, Wei Zheng, Mariana C. Stern, Cecelia A. Laurie, Jing Ma, Cornelia M. Ulrich, Stephanie L. Schmit, Victor Moreno, John D. Potter, Chenxu Qu, Bette J. Caan, Heinz-Josef Lenz, M. Henar Alonso, Andrea Z. LaCroix, Christoph Mancao, John F. Harju, Yun Ru Liu, Jane C. Figueiredo, Gregory Idos, Kana Wu, Duncan C. Thomas, Motoki Iwasaki, W. James Gauderman, Thomas A. Sellers, David Van Den Berg, Barbara K. Fortini, David N. Levine, James M. Church, Ya Wen Cheng, Edith J. M. Feskens, Edward Giovannucci, Manish Gala, Polly A. Newcomb, Charles Kooperberg, Iona Cheng, David J. Hunter, Martha L. Slattery, Roger L. Milne, Lars G. Fritsche, Niha Zubair, Steven Gallinger, Yi Xin Zeng, Wei Shi, Andrew T. Chan, Fotios Loupakis, Vittorio Krogh, Clemens Schafmayer, Sun-Seog Kweon, Bethany van Guelpan, Amanda Bloomer, Kenneth Offit, Stephanie Tring, Shoichiro Tsugane, David Duggan, Fredrick R. Schumacher, Joseph Vijai, Weihua Jia, Marie-Christine Boutron-Ruault, Joel K. Greenson, Frank Luh, Ulrike Peters, Keith R. Curtis, Juergen Boehm, Robert E. Schoen, Sonja I. Berndt, Elizabeth L. Barry, Sebastian Stintzing, Li Hsu, Emily White, Conghui Qu, Peter T. Campbell, Caroline McNeil, and Yun Yen
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Oncology ,Cancer Research ,medicine.medical_specialty ,Genotype ,Nutrition and Disease ,Colorectal cancer ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Càncer colorectal ,Internal medicine ,Voeding en Ziekte ,Ethnicity ,medicine ,Genetic predisposition ,Genetics ,Humans ,Life Science ,Genetic Predisposition to Disease ,Oncology & Carcinogenesis ,Allele ,Allele frequency ,Genetic association ,VLAG ,Global Nutrition ,Wereldvoeding ,Oncology And Carcinogenesis ,Case-control study ,Articles ,Prognosis ,medicine.disease ,United States ,3. Good health ,Genetic Loci ,Case-Control Studies ,030220 oncology & carcinogenesis ,Colorectal Neoplasms ,Genètica ,Follow-Up Studies ,Genome-Wide Association Study - Abstract
Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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- 2019
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26. Implementation Protocol Utilising Radio Frequency Identification (RFID) and Biometric Identifiers; In the Context of Irish Bovine Traceability
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Conor Shanahan, Shane Ward, Kevin McDonnell, Francis Butler, and Gashaw Ayalew
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Protocol (science) ,Engineering ,education.field_of_study ,Population statistics ,Traceability ,business.industry ,Population ,Context (language use) ,Computer security ,computer.software_genre ,language.human_language ,Identification (information) ,Irish ,language ,Radio-frequency identification ,Operations management ,business ,education ,computer - Abstract
1.1 Irish cattle traceability The Irish Department of Agriculture, Fisheries and Food (DAFF) is the authority responsible for the implementation of EC 1760/2000, which outlines the requirements for the identification and registration of bovine animals. Since the mid 1990’s computerised databases have been established specifically the Calf Birth Registration System and the Cattle Movement Monitoring System (CMMS) (DAFF, 2003). The CMMS was initiated to record all information on births, movement, deaths and disposals. Computer equipment linked to the central database was installed in abattoirs and export points to electronically record all animal movements to and/or from these premises. As the CMMS relies on paper records for notification of certain events such as, births (herd keepers have seven days to notify the Calf Birth Registration System) and on-farm deaths, it cannot be said that it is totally accurate at a given point in time. The figures from the official CMMS statistics reports published each year reflect this, out of which a summary of the herd population statistics for recent years can be seen in Table 1. The start of January figures are calculated by taking the population figure at the end of December for the year in question from the CMMS database and adding all the disposals (cattle slaughtered, exported and on-farm deaths) and subtracting all the births and imports that have been recorded on the CMMS for that year.
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- 2021
27. Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist
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Eric Haines, Katerine Van Rietschoten, Punit Upadhyaya, Marianna Kleyman, Elizabeth Repash, Tom Li Stephen, Jessica Kublin, Johanna Lahdenranta, Sailaja Battula, Rachel Dods, Kristen Hurov, Jun Ma, Nicholas Keen, Rachid Lani, Gemma Mudd, Philip Brandish, Julia Kristensson, Kevin Mcdonnell, Helen Harrison, Liuhong Chen, and Fanglei You
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,CD8-Positive T-Lymphocytes ,Jurkat Cells ,Mice ,0302 clinical medicine ,Cancer immunotherapy ,Neoplasms ,Tumor Microenvironment ,Immunology and Allergy ,RC254-282 ,Chemistry ,Receptor, EphA2 ,CD137 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,adaptive immunity ,Acquired immune system ,Tumor antigen ,costimulatory and inhibitory t-cell receptors ,Oncology ,030220 oncology & carcinogenesis ,PC-3 Cells ,Molecular Medicine ,Female ,immunotherapy ,HT29 Cells ,Immunology ,Mice, Transgenic ,Peptides, Cyclic ,03 medical and health sciences ,Tumor Necrosis Factor Receptor Superfamily, Member 9 ,Immune system ,Antigen ,Antigens, Neoplasm ,Peptide Library ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pharmacology ,Tumor microenvironment ,Basic Tumor Immunology ,Immunotherapy ,Receptors, OX40 ,Xenograft Model Antitumor Assays ,030104 developmental biology ,A549 Cells ,Cancer research - Abstract
BackgroundIn contrast to immune checkpoint inhibitors, the use of antibodies as agonists of immune costimulatory receptors as cancer therapeutics has largely failed. We sought to address this problem using a new class of modular synthetic drugs, termed tumor-targeted immune cell agonists (TICAs), based on constrained bicyclic peptides (Bicycles).MethodsPhage libraries displaying Bicycles were panned for binders against tumor necrosis factor (TNF) superfamily receptors CD137 and OX40, and tumor antigens EphA2, Nectin-4 and programmed death ligand 1. The CD137 and OX40 Bicycles were chemically conjugated to tumor antigen Bicycles with different linkers and stoichiometric ratios of binders to obtain a library of low molecular weight TICAs (MW in vitro and in vivo assays to characterize their pharmacology and mechanism of action.ResultsLinking Bicycles against costimulatory receptors (e.g., CD137) to Bicycles against tumor antigens (e.g., EphA2) created potent agonists that activated the receptors selectively in the presence of tumor cells expressing these antigens. An EphA2/CD137 TICA (BCY12491) efficiently costimulated human peripheral blood mononuclear cells in vitro in the presence of EphA2 expressing tumor cell lines as measured by the increased secretion of interferon γ and interleukin-2. Treatment of C57/Bl6 mice transgenic for the human CD137 extracellular domain (huCD137) bearing EphA2-expressing MC38 tumors with BCY12491 resulted in the infiltration of CD8+ T cells, elimination of tumors and generation of immunological memory. BCY12491 was cleared quickly from the circulation (plasma t1/2 in mice of 1–2 hr), yet intermittent dosing proved effective.ConclusionTumor target-dependent CD137 agonism using a novel chemical approach (TICAs) afforded elimination of tumors with only intermittent dosing suggesting potential for a wide therapeutic index in humans. This work unlocks a new path to effective cancer immunotherapy via agonism of TNF superfamily receptors.
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- 2021
28. Impact of field headlands on wheat and barley performance in a cool Atlantic climate as assessed in 40 Irish tillage fields
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Mark Ward, P. D. Forristal, and Kevin McDonnell
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business.product_category ,Soil texture ,Grain fields ,Headland ,Crop ,Plough ,03 medical and health sciences ,Yield (wine) ,030304 developmental biology ,0303 health sciences ,geography ,geography.geographical_feature_category ,Ecology ,Crop performance ,Crop yield ,04 agricultural and veterinary sciences ,Tillage ,Agronomy ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Environmental science ,Animal Science and Zoology ,Interception ,business ,Agronomy and Crop Science ,Ireland ,Food Science - Abstract
The reduction in cereal crop yields on field headlands has previously been examined in other geographical regions, with research focusing on the relationship between yield and the distance from the crop edge. Headlands are subject to greater machinery trafficking than the centre of the field and the level of traffic imposed depends on the machine size and adopted turning practice. The aim of this work was to examine the impact of turning headlands on crop performance in a survey of 40 field sites in Irish conditions. The headland was categorised into three distinct zones: the area next to the field edge subject to moderate traffic intensities (field edge); the main headland area of greatest turning traffic (turning) and a transition zone (transition). An in-field zone (in-field) in which no machinery turns occur was also included. The 2-year survey included sites from three regions, four soil texture classes and had crops established with plough-based systems. Crop measurements, including plant densities, shoot counts and light interception, and yields were recorded at each site and included winter barley (WB), spring barley (SB) and winter wheat (WW) crops. The yield response of each crop type varied with sample zone, region and soil texture. There were significant (P < 0.001) yield differences recorded between the turning area and in-field zone for all three crops. Winter barley yields were reduced by 1.3 t/ha in the turning zone compared with the in-field section, while SB and WW had yield reductions of 2.08 and 4.04 t/ha, respectively, between these two field zones. Department of Agriculture, Food and the Marine
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- 2020
29. Feasibility Study of Carbon Dioxide Plume Geothermal Systems in Germany−Utilising Carbon Dioxide for Energy
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Mary Harty, Fionnuala Murphy, Levente Molnár, and Kevin McDonnell
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Control and Optimization ,Geothermal ,020209 energy ,Energy Engineering and Power Technology ,02 engineering and technology ,Carbon sequestration ,010502 geochemistry & geophysics ,lcsh:Technology ,01 natural sciences ,carbon capture and utilization ,Germany ,geothermal ,0202 electrical engineering, electronic engineering, information engineering ,Carbon capture and storage ,media_common.cataloged_instance ,Electrical and Electronic Engineering ,European union ,Cost of electricity by source ,Engineering (miscellaneous) ,0105 earth and related environmental sciences ,media_common ,coal ,Carbon capture and utilisation ,lcsh:T ,Renewable Energy, Sustainability and the Environment ,business.industry ,Geothermal energy ,Fossil fuel ,Environmental engineering ,carbon dioxide ,Sequestration ,sequestration ,Renewable energy ,Coal ,Carbon dioxide ,Greenhouse gas ,Environmental science ,business ,Energy (miscellaneous) - Abstract
To manage greenhouse gas emissions, directives on renewable energy usage have been developed by the European Commission with the objective to reduce overall emissions by 40% by 2030 which presents a significant potential for renewable energy sources. At the same time, it is a challenge for these energy technologies which can only be solved by integrated solutions. Carbon capture and storage combined with geothermal energy could serve as a novel approach to reduce CO2 emissions and at the same time facilitate some of the negative impacts associated with fossil fuel-based power plants. This study focuses on the technical and economic feasibility of combining these technologies based on a published model, data and market research. In the European Union, Germany is the most energy intensive country, and it also has an untapped potential for geothermal energy in the northern as well as the western regions. The CO2 plume geothermal system using supercritical carbon dioxide as the working fluid can be utilized in natural high porosity (10&ndash, 20%) and permeability (2.5 ×, 10&minus, 14&ndash, 8.4 ×, 16 m2) reservoirs with temperatures as low as 65.8 °, C. The feasibility of the project was assessed based on market conditions and policy support in Germany as well as the geologic background of sandstone reservoirs near industrialized areas (Dortmund, Frankfurt) and the possibility of carbon capture integration and CO2 injection. The levelized cost of electricity for a base case results in &euro, 0.060/kWh. Optimal system type was assessed in a system optimization model. The project has a potential to supply 6600/12000 households with clean energy (electricity/heat) and sequester carbon dioxide at the same time. A trading scheme for carbon dioxide further expands potential opportunities.
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- 2020
30. DBNS: A Distributed Blockchain-Enabled Network Slicing Framework for 5G Networks
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Kapal Dev, Ting Bi, Mohammed Amine Togou, Hitesh Tewari, Kevin McDonnell, Gabriel-Miro Muntean, and Aleksandar Milenovic
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Flexibility (engineering) ,Service (systems architecture) ,Mobile edge computing ,Computer Networks and Communications ,Computer science ,Reliability (computer networking) ,Distributed computing ,020206 networking & telecommunications ,02 engineering and technology ,Admission control ,Bidding ,Computer Science Applications ,Resource (project management) ,Software deployment ,High availability ,0202 electrical engineering, electronic engineering, information engineering ,Electrical and Electronic Engineering - Abstract
5G technology is expected to enable many innovative applications in different verticals. These applications have heterogeneous performance requirements (e.g., high data rate, low latency, high reliability, and high availability). In order to meet these requirements, 5G networks endorse network flexibility through the deployment of new emerging technologies, mainly network slicing and mobile edge computing. This article introduces a distributed blockchain-enabled network slicing (DBNS) framework that enables service and resource providers to dynamically lease resources to ensure high performance for their end-to-end services. The key component of our framework is global service provisioning, which provides admission control for incoming service requests along with dynamic resource assignment by means of a blockchain-based bidding system. The goal is to improve users’ experience with diverse services and reduce providers’ capital and operational expenditure.
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- 2020
31. Microgeneration of Electricity Using a Solar Photovoltaic System in Ireland
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Mary Harty, Kevin McDonnell, and Vinay Virupaksha
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Renewable energy ,Control and Optimization ,Microgeneration ,020209 energy ,Energy Engineering and Power Technology ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,Load profile ,Peak demand ,Solar energy ,0202 electrical engineering, electronic engineering, information engineering ,Electrical and Electronic Engineering ,Engineering (miscellaneous) ,0105 earth and related environmental sciences ,Renewable Energy, Sustainability and the Environment ,business.industry ,Photovoltaic system ,Environmental economics ,Crowd funding ,Environmental science ,Electricity ,business ,Embodied energy ,Photovoltaic ,Energy (miscellaneous) ,microgeneration ,solar energy ,photovoltaic ,renewable energy ,crowd funding - Abstract
Microgeneration of electricity using solar photovoltaic (PV) systems is a sustainable form of renewable energy, however uptake in Ireland remains very low. The aim of this study is to assess the potential of the community-based roof top solar PV microgeneration system to supply electricity to the grid, and to explore a crowd funding mechanism for community ownership of microgeneration projects. A modelled microgeneration project was developed: the electricity load profiles of 68 residential units were estimated; a community-based roof top solar PV system was designed; an electricity network model, based on a real network supplying a town and its surrounding areas, was created; and power flow analysis on the electrical network for system peak and minimum loads was carried out. The embodied energy, energy payback time, GHG payback time, carbon credits and financial cost relating to the proposed solar PV system were calculated. Different crowdfunding models were assessed. Results show the deployment of community solar PV system projects have significant potential to reduce the peak demand, smooth the load profile, assist in the voltage regulation and reduce electrical losses and deliver cost savings to distribution system operator and the consumer.
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- 2019
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32. Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk
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Brent Evans, James M. Ford, Richard J. Wenstrup, Julie O. Culver, Courtney Rowe-Teeter, Meredith A. Mills, Peter Levonian, Uri Ladabaum, Nicolette M. Chun, Charité Ricker, Katrina Lowstuter, Bhramar Mukherjee, Cindy Ma, Rachel Koff, Brian Allen, Kerry Kingham, Iva Petrovchich, Duveen Sturgeon, Katlyn Partynski, Krystal Brown, Anne-Renee Hartman, Christine Hong, Allison W. Kurian, Kevin McDonnell, John Kidd, Stephen B. Gruber, Johnathan M. Lancaster, Alexandra Lebensohn, and Gregory Idos
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Yield (finance) ,Cancer susceptibility ,Germline ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Gene panel ,Patient experience ,Medicine ,Original Report ,Multiplex ,Hereditary Cancer ,business ,Prospective cohort study - Abstract
Purpose Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations. Patients and Methods This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics—University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute—who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate). Results Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested. Conclusion In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results.
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- 2019
33. Effect of Harvest Timing and Soil Moisture Content on Compaction, Growth and Harvest Yield in a Miscanthus Cropping System
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Kevin McDonnell, M. G. O'Flynn, Edna M. Curley, John Finnan, Science Foundation Ireland, and CP/E001
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Compaction ,Plant Science ,Miscanthus ,010501 environmental sciences ,01 natural sciences ,compaction ,Cropping system ,lcsh:Agriculture (General) ,Water content ,0105 earth and related environmental sciences ,biology ,Soil classification ,04 agricultural and veterinary sciences ,biology.organism_classification ,repeated trafficking ,Bulk density ,lcsh:S1-972 ,Agronomy ,Shoot ,Repeated trafficking ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Environmental science ,Gleysol ,Agronomy and Crop Science ,Food Science - Abstract
Harvesting Miscanthus ×, giganteus (J.M. Greef &, Deuter ex Hodkinson &, Renvoize) after shoot emergence is known to reduce yields in subsequent seasons. This research was conducted in Miscanthus to assess the effects on crop response and soil compaction of annually repeated traffic, applied both before new growth in the rhizomes (early harvest) and after shoot emergence (late harvest), at two different soil moisture contents. While an annual early harvest, yields more than a late harvest, because damage to new shoots is avoided, soil compaction may be increased following repeated harvests. Five treatments were tested: (a) An untrafficked control, (b) early-traffic on soil with typical soil moisture content (SMC) (early-normal), (c) early-traffic on soil with elevated SMC (early-elevated), (d) late-traffic on soil with typical SMC (late-normal) and (e) late-traffic on soil with elevated SMC (late-wet). The experiment was conducted on a Gleysol in Co. Dublin, Ireland during 2010 and 2011. Crop response effects were assessed by measuring stem numbers, stem height, trafficked zone biomass yield (November) and overall stem yield (January). Compaction effects were assessed by measuring penetration resistance, bulk density and water infiltration rate. Trafficked zone biomass yield in the early-dry and early-wet treatments was, respectively, 18% and 23% lower than in the control, but was, respectively, 39% and 31% higher than in the late-dry treatment. Overall, stem yield was significantly lower in the late-normal and late-wet treatments (10.4 and 10.1 tdm ha&minus, 1 respectively) when compared with the control (12.4 tdm ha&minus, 1), but no significant difference was recorded in overall stem yield between both early-traffic treatments and the control. Penetration resistance values were significantly higher in all trafficked treatments when compared with the control at depths of 0.15 m (&ge, 54&ndash, 61%) and 0.30 m (&ge, 27&ndash, 57%) and were significantly higher in 2011 when compared with 2010 at depths of 0.15 and 0.30 m. Baler system traffic in Miscanthus significantly reduced yields and significantly increased compaction annually. Miscanthus harvested early, on a dry soil, yielded 1.1 tdm ha&minus, 1 more than when harvested late on a dry soil. The yield advantage increased to 1.3 tdm ha&minus, 1 when early harvesting on a soil with 40&ndash, 43% moisture content was compared with late harvesting on a wetter soil (51&ndash, 52% moisture content). In this study, the magnitude of yield losses from compaction or other causes in early harvests was substantially lower than the yield losses, which resulted from shoot damage in late harvests. It is likely in similar climates that the results of this study would also apply to other perennial crops growing in similar soil types.
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- 2018
34. A human MUTYH variant linking colonic polyposis to redox degradation of the [4Fe4S]²⁺ cluster
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Stephen B. Gruber, Joseph A. Chemler, Jacqueline K. Barton, Elizabeth O’Brien, Ralph H. Stern, Monica L. Marvin, Leon Raskin, Guo Min Li, David H. Sherman, Janice Ortega, Phillip L. Bartels, and Kevin McDonnell
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Iron-Sulfur Proteins ,0301 basic medicine ,General Chemical Engineering ,Eukaryotic DNA replication ,Oxidative phosphorylation ,medicine.disease_cause ,DNA Glycosylases ,Cancer syndrome ,03 medical and health sciences ,chemistry.chemical_compound ,MUTYH ,Genetics ,medicine ,Humans ,Cancer ,Mutation ,030102 biochemistry & molecular biology ,Chemistry ,Organic Chemistry ,Tryptophan ,Genetic Variation ,General Chemistry ,medicine.disease ,Molecular biology ,Colo-Rectal Cancer ,030104 developmental biology ,Adenomatous Polyposis Coli ,Colonic Neoplasms ,Chemical Sciences ,Generic health relevance ,Digestive Diseases ,Oxidation-Reduction ,DNA ,Cysteine - Abstract
The human DNA repair enzyme MUTYH excises mispaired adenine residues in oxidized DNA. Homozygous MUTYH mutations underlie the autosomal, recessive cancer syndrome MUTYH-associated polyposis. We report a MUTYH variant, p.C306W (c.918C>G), with a tryptophan residue in place of native cysteine, that ligates the [4Fe4S] cluster in a patient with colonic polyposis and family history of early age colon cancer. In bacterial MutY, the [4Fe4S] cluster is redox active, allowing rapid localization to target lesions by long-range, DNA-mediated signalling. In the current study, using DNA electrochemistry, we determine that wild-type MUTYH is similarly redox-active, but MUTYH C306W undergoes rapid oxidative degradation of its cluster to [3Fe4S]+, with loss of redox signalling. In MUTYH C306W, oxidative cluster degradation leads to decreased DNA binding and enzyme function. This study confirms redox activity in eukaryotic DNA repair proteins and establishes MUTYH C306W as a pathogenic variant, highlighting the essential role of redox signalling by the [4Fe4S] cluster.
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- 2018
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35. Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury
- Author
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Atsushi Mizoguchi, Jonathan J. Hubbard, Sanda Win, Neil Kaplowitz, Shalaka Purohit, Kevin Mcdonnell, Zachary Taylor, Thomas D Krämer, Jan Terje Andersen, Richard S. Blumberg, Kristi Baker, Inger Sandlie, Timothy Kuo, Michal Pyzik, Vicki L. Nienaber, Timo Rath, Rosa Grenha, Adam R. Mezo, Gregory J. Christianson, Amit Gandhi, Derry C. Roopenian, Laurence J. Blumberg, Susan D. Jones, and Wayne I. Lencer
- Subjects
0301 basic medicine ,Male ,Endosome ,Serum albumin ,Serum Albumin, Human ,Receptors, Fc ,Biology ,Madin Darby Canine Kidney Cells ,03 medical and health sciences ,Dogs ,Albumins ,medicine ,Animals ,Bile ,Homeostasis ,Hypoalbuminemia ,Receptor ,Acetaminophen ,Mice, Inbred BALB C ,Multidisciplinary ,Histocompatibility Antigens Class I ,Albumin ,medicine.disease ,Mice, Mutant Strains ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Biochemistry ,Transcytosis ,PNAS Plus ,Hepatocyte ,biology.protein ,Hepatocytes ,Female ,Chemical and Drug Induced Liver Injury ,Intracellular - Abstract
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood. Here we demonstrate that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrate that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determines the physiologic release of newly synthesized albumin into the basal milieu. These properties allow hepatic FcRn to mediate albumin delivery and maintenance in the circulation, but they also enhance sensitivity to the albumin-bound hepatotoxin, acetaminophen (APAP). As such, global or liver-specific deletion of FcRn results in resistance to APAP-induced liver injury through increased albumin loss into the bile and increased intracellular albumin scavenging of reactive oxygen species. Further, protection from injury is achieved by pharmacologic blockade of FcRn–albumin interactions with monoclonal antibodies or peptide mimetics, which cause hypoalbuminemia, biliary loss of albumin, and increased intracellular accumulation of albumin in the hepatocyte. Together, these studies demonstrate that the main function of hepatic FcRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity.
- Published
- 2017
36. A Feasibility Assessment of Photovoltaic Power Systems in Ireland; a Case Study for the Dublin Region
- Author
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Fionnuala Murphy and Kevin McDonnell
- Subjects
Engineering ,Primary energy ,020209 energy ,Geography, Planning and Development ,TJ807-830 ,02 engineering and technology ,Management, Monitoring, Policy and Law ,solar PV ,TD194-195 ,Renewable energy sources ,Grid parity ,Time ,Energy payback ,Greenhouse gas emissions ,0202 electrical engineering, electronic engineering, information engineering ,GE1-350 ,energy payback time ,Feed-in tariff ,Life-cycle assessment ,economic payback time ,Economic payback time ,Ireland ,greenhouse gas emissions ,feasibility ,Environmental effects of industries and plants ,Waste management ,Renewable Energy, Sustainability and the Environment ,business.industry ,Photovoltaic system ,Feasibility ,Environmental economics ,Renewable energy ,Environmental sciences ,Electricity generation ,Solar PV ,Electricity ,business - Abstract
Photovoltaic (PV) power generation is one of the cleanest sources for producing renewable energy; however uptake on the Irish renewable energy market to date has been low. There is a lack of support for solar PV systems in Ireland; there is currently no solar PV energy feed-in-tariff as there are for other renewable energy systems in Ireland. Despite the current lack of support, the Government has indicated that support for the uptake of solar PV installations will be provided through the provision of a feed-in tariff in the future. The aim of this study was to determine the feasibility of installing PV systems under Irish climatic conditions at a location based in Dublin, Ireland, from a technical, environmental and economic point of view. This was achieved by carrying out a life cycle assessment of potential environmental impacts, and analysis of energy and economic payback times relating to the proposed PV system. Four possible renewable feed-in-tariffs (based on existing feed-in-tariffs for other renewable energy systems) were considered to determine the effect of such tariffs on the overall economics of the proposed PV system. Results show that life cycle GHG emissions are 69 g CO2-eq per kWh generated by the system, significantly lower than the current electricity grid mix emissions of 469 g CO2-eq per kWh. It will take 5.23 years of operation of the solar plant to generate the same amount of energy (in terms of primary energy equivalent) that was used to produce the system itself. The economic payback time varies from 19.3 and 34.4 years depending on the rate of renewable energy feed-in-tariff applied. The costs for the production of PV electricity in this study are higher than is usual in countries where the solar PV market is more developed, e.g., Germany, due to constraints with building integration and lack of experienced PV installers. As more PV is deployed, the Irish PV installer base will increase and ‘learning by doing’ effects will allow installers to install projects more efficiently and quickly under Irish conditions, leading to significantly reduced costs. Science Foundation Ireland
- Published
- 2017
- Full Text
- View/download PDF
37. Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38
- Author
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Elizaveta Andrianova, Zhaolin Wang, Zachary Minden, Ratul Mukerji, Carlos Tassa, Kevin McDonnell, Scott Paul Lentini, Stephen S. Scully, Susan Low, and James Kaberna
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,medicine.drug_class ,Organic Chemistry ,Alkyne ,CD38 ,Monoclonal antibody ,Biochemistry ,Combinatorial chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Drug Discovery ,medicine ,Amine gas treating ,Fluorescein ,Surface plasmon resonance ,Conjugate - Abstract
Several monoclonal antibodies and inhibitors targeting CD38, an ectoenzyme overexpressed on malignant plasma cells, have previously been discovered. Herein, we expand structure–activity relationships of reported small-molecule thiazoloquinolinones and show that several 4-cyclohexylamino analogues have potent binding affinity for CD38 using surface plasmon resonance. Moreover, active amine analogues could be acylated and functionalized with alkyne and fluorescein groups. Fluorescein analogue 21 bound selectively to CD38 overexpressing cells, demonstrating the potential utility of thiazoloquinolinones as small-molecule conjugates for the delivery of therapeutic and imaging agents.
- Published
- 2016
38. 111In- and IRDye800CW-Labeled PLA–PEG Nanoparticle for Imaging Prostate-Specific Membrane Antigen-Expressing Tissues
- Author
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Martin G. Pomper, Sangeeta Ray Banerjee, Catherine A. Foss, Allen Horhota, Kevin McDonnell, Mrudula Pullambhatla, and Stephen E. Zale
- Subjects
Biodistribution ,Fluorescence-lifetime imaging microscopy ,Polymers and Plastics ,Nanoparticle ,Bioengineering ,Nanotechnology ,02 engineering and technology ,urologic and male genital diseases ,Article ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Materials Chemistry ,Glutamate carboxypeptidase II ,medicine ,Moiety ,Chemistry ,Cancer ,021001 nanoscience & nanotechnology ,medicine.disease ,Molecular biology ,Lactic acid ,030220 oncology & carcinogenesis ,0210 nano-technology - Abstract
Targeted delivery of drug-encapsulated nanoparticles is a promising new approach to safe and effective therapeutics for cancer. Here we investigate the pharmacokinetics and biodistribution of a prostate-specific membrane antigen (PSMA)-targeted nanoparticle based on a poly(lactic acid)–polyethylene glycol copolymer by utilizing single photon emission computed tomography (SPECT) and fluorescence imaging of a low-molecular-weight, PSMA-targeting moiety attached to the surface and oriented toward the outside environment. Tissue biodistribution of the radioactive, PSMA-targeted nanoparticles in mice containing PSMA(+) PC3 PIP and PSMA(−) PC3 flu (control) tumors demonstrated similar accumulation compared to the untargeted particles within all tissues except for the tumor and liver by 96 h postinjection. For PSMA(+) PC3 PIP tumor, the targeted nanoparticle demonstrated retention of 6.58% injected dose (ID)/g at 48 h and remained nearly at that level out to 96 h, whereas the untargeted nanoparticle showed a 48 h retention of 8.17% ID/g followed by a significant clearance to 2.37% ID/g at 96 h (P < 0.02). On the other hand, for control tumor, both targeted and untargeted particles displayed similar 48 h retentions and rates of clearance over 96 h. Ex vivo microscopic analysis with near-infrared versions of the nanoparticles indicated retention within PSMA(+) tumor epithelial cells as well as tumor-associated macrophages for targeted particles and primarily macrophage-associated uptake for the untargeted particles. Retention in control tumor was primarily associated with tumor vasculature and macrophages. The data demonstrate the utility of radioimaging to assess nanoparticle biodistribution and suggest that active targeting has a modest positive effect on tumor localization of PSMA-targeted PLA–PEG nanoparticles that have been derivatized for imaging.
- Published
- 2016
39. A novel method for metal–diamond composite coating deposition with cold spray and formation mechanism
- Author
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Barry Aldwell, Shuo Yin, Tanvir Hussain, Rocco Lupoi, D. Trimble, and Kevin McDonnell
- Subjects
Materials science ,XRD ,Composite number ,Gas dynamic cold spray ,02 engineering and technology ,engineering.material ,Raw material ,01 natural sciences ,Metal ,Coating ,0103 physical sciences ,Deposition (phase transition) ,General Materials Science ,Coated particle ,010302 applied physics ,Mechanical Engineering ,Metallurgy ,Metals and Alloys ,Diamond ,Cold spray ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Composite coating ,Mechanics of Materials ,visual_art ,engineering ,visual_art.visual_art_medium ,0210 nano-technology - Abstract
This paper describes the application of cold spray to the deposition of a diamond grade pre-coated with Cu and Ni. This is the first time that pre-coated diamond powders are used as the sole feedstock without the addition of binders (ductile phases) in cold spraying. The experimental results showed that it was possible to manufacture thick metal–diamond composite coatings onto an Al alloy substrate with high diamond fraction in the coating and without phase change. Results from this paper also have demonstrated a new methodology for the deposition of metal–diamond/ceramic composite coating with the cold spray technique.
- Published
- 2016
40. Increased Yield of Actionable Mutations Using Multi-Gene Panels to Assess Hereditary Cancer Susceptibility in an Ethnically Diverse Clinical Cohort
- Author
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Kevin McDonnell, William J. Gauderman, Katrina Lowstuter, Julia D. Sturgeon, Stephen B. Gruber, Julie O. Culver, Charité Ricker, Christopher R. Chanock, Duveen Sturgeon, and Gregory Idos
- Subjects
0301 basic medicine ,Male ,Cancer Research ,medicine.medical_specialty ,030105 genetics & heredity ,Biology ,Risk Assessment ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Neoplasms ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,First-degree relatives ,Family history ,Molecular Biology ,Genetic testing ,Retrospective Studies ,medicine.diagnostic_test ,Cancer ,Retrospective cohort study ,Heritability ,respiratory system ,Middle Aged ,medicine.disease ,030220 oncology & carcinogenesis ,Mutation ,Female ,Risk assessment ,human activities ,Cohort study - Abstract
This study aims to assess multi-gene panel testing in an ethnically diverse clinical cancer genetics practice. We conducted a retrospective study of individuals with a personal or family history of cancer undergoing clinically indicated multi-gene panel tests of 6-110 genes, from six commercial laboratories. The 475 patients in the study included 228 Hispanics (47.6%), 166 non-Hispanic Whites (35.4%), 55 Asians (11.6%), 19 Blacks (4.0%), and seven others (1.5%). Panel testing found that 15.6% (74/475) of patients carried deleterious mutations for a total of 79 mutations identified. This included 7.4% (35/475) of patients who had a mutation identified that would not have been tested with a gene-by-gene approach. The identification of a panel-added mutation impacted clinical management for most of cases (69%, 24/35), and genetic testing was recommended for the first degree relatives of nearly all of them (91%, 32/35). Variants of uncertain significance (VUSs) were identified in a higher proportion of tests performed in ethnic minorities. Multi-gene panel testing increases the yield of mutations detected and adds to the capability of providing individualized cancer risk assessment. VUSs represent an interpretive challenge due to less data available outside of White, non-Hispanic populations. Further studies are necessary to expand understanding of the implementation and utilization of panels across broad clinical settings and patient populations.
- Published
- 2016
41. The Impact of Field Size on the Environment and Energy Crop Production Efficiency for a Sustainable Indigenous Bioenergy Supply Chain in the Republic of Ireland
- Author
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Ger Devlin, Kevin McDonnell, and Rory Deverell
- Subjects
Economics ,Supply chain ,Geography, Planning and Development ,TJ807-830 ,Management, Monitoring, Policy and Law ,bioenergy ,TD194-195 ,Renewable energy sources ,Environmental protection ,Bioenergy ,jel:Q ,habitats ,carbon ,economics ,GE1-350 ,Environmental effects of industries and plants ,Renewable Energy, Sustainability and the Environment ,Agroforestry ,business.industry ,jel:Q0 ,jel:Q2 ,Soil type ,jel:Q3 ,Carbon ,jel:Q5 ,Habitats ,Renewable energy ,Energy crop ,Environmental sciences ,Agriculture ,jel:O13 ,Sustainability ,Environmental science ,jel:Q56 ,business ,Energy source - Abstract
This paper investigates, using the GIS platform, the potential impacts of meeting national bioenergy targets using only indigenous sources of feedstock on the habitats and carbon stores that exist within Ireland’s field boundaries. A survey of the Republic of Irelands field was conducted in order to estimate and map the size and geographic distribution of the Republic of Ireland’s field boundaries. The planting and harvesting costs associated with possible bioenergy crop production systems were determined using the relationship between the seasonal operating efficiency and the average field size. The results indicate that Ireland will need a large proportion of its current agricultural area (at least 16.5%) in order to its meet national bioenergy targets by 2020. The demand cannot be met by the current area that both has suitable soil type for growing the bioenergy crops and is large enough for the required operating efficiency. The results of this study indicate that implementing and meeting national bioenergy targets using only indigenous feedstock will likely impact the country’s field boundary resources negatively, as crop producers seek to improve production efficiency through field consolidation and field boundary removal. It was found that such boundary removal results in a loss of up to 6 tC/km2 and 0.7 ha/km of previously permanent habitat where average field size is small. The impact of field consolidation on these resources reduces substantially as larger fields become consolidated. Department of Agriculture, Fisheries and Food
- Published
- 2009
42. Managing the moisture content of wood biomass for the optimisation of Ireland's transport supply strategy to bioenergy markets and competing industries
- Author
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Mauricio Acuna, Ger Devlin, Kevin McDonnell, and Amanda Sosa
- Subjects
Moisture content ,Engineering ,Power station ,Supply chain ,Biomass ,Agricultural engineering ,Competing demands ,Industrial and Manufacturing Engineering ,Transportation supply optimisation ,Bioenergy ,Biomass allocation ,Spatial distribution ,Electrical and Electronic Engineering ,Water content ,Civil and Structural Engineering ,Waste management ,business.industry ,Mechanical Engineering ,Building and Construction ,Pollution ,Renewable energy ,General Energy ,Biofuel ,Woodchips ,business ,Ireland - Abstract
The aim of this study was to analyse the supply of wood biomass (short wood) to the three peat power plants in Ireland and the impacts on the competing wood-based panel industries. The methodology includes the development of a spatial decision support tool based on LP (Linear Programming). It uses drying curves to assess the moisture content, weight and energy content of biomass during a two year period planning. Harvesting, chipping, storage and transportation costs are calculated based on the biomass moisture content. The model optimally allocates woodchips and logs from thinnings and clearfells. Results show that the planned maximum 30% co-firing rate at the three peat power station could be met with the forecasted short wood availability from both the private and public sector. The costs of supply increased not only with higher demands, but also with tighter constraints on the MC demanded by power plants. Spatial distribution and operational factors such as efficiency in transportation and truck loading showed to be sensitive to changes in MC. The analysis shows the benefits of managing the MC when optimising supply chains in order to deliver biomass to energy plants in a cost-effective manner. Science Foundation Ireland CoFoRD Charles Parsons Energy Research Program
- Published
- 2015
43. Benchmarking Environmental Impacts of Peat Use for Electricity Generation in Ireland—A Life Cycle Assessment
- Author
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Fionnuala Murphy, Ger Devlin, and Kevin McDonnell
- Subjects
Peat ,Geography, Planning and Development ,Climate change ,TJ807-830 ,Management, Monitoring, Policy and Law ,TD194-195 ,Renewable energy sources ,jel:Q ,Greenhouse gas emissions ,Environmental impact assessment ,GE1-350 ,Life-cycle assessment ,Energy ,Environmental effects of industries and plants ,Renewable Energy, Sustainability and the Environment ,business.industry ,greenhouse gas emissions ,LCA ,Fossil fuel ,Global warming ,Environmental engineering ,jel:Q0 ,environmental impacts ,Environmental impacts ,jel:Q2 ,jel:Q3 ,jel:Q5 ,Environmental sciences ,Electricity generation ,peat ,energy ,Ireland ,jel:O13 ,Greenhouse gas ,Environmental science ,jel:Q56 ,business - Abstract
The combustion of peat for energy generation accounts for approximately 4.1% of Ireland’s overall greenhouse gas (GHG) emissions, with current levels of combustion resulting in the emission of 2.8 Mt of CO2 per annum. The aim of this research is to evaluate the life cycle environmental impacts of peat use for energy generation in Ireland, from peatland drainage and industrial extraction, to transportation, combustion, and subsequent after-use of the cutaway area, utilising Irish-specific emission factors. The environmental impacts considered are global warming potential, acidification potential, and eutrophication potential. In addition, the cumulative energy demand of the system is evaluated. Previous studies on the environmental impact of peat for energy in Ireland relied on default Intergovernmental Panel on Climate Change (IPCC) emission factors (EFs). This research utilises Irish-specific EFs and input data to reduce uncertainty associated with the use of default IPCC EFs, and finds that using default IPCC EFs overestimates the global warming potential when compared to Irish-specific EFs by approximately 2%. The greatest contribution to each of the environmental impacts considered arises from emissions generated during peat combustion, which accounts for approximately 95% of each of the environmental impact categories considered. Other stages of the life-cycle, such as impacts emanating from the peat extraction area, fossil fuel usage in harvesting and transportation machinery, and after-use of the cutaway area have much smaller effects on overall results. The transformation of cutaway peatlands to different after-use alternatives has the potential to mitigate some of the effects of peatland degradation and peat combustion. Science Foundation Ireland Charles Parsons Energy Research Programme
- Published
- 2015
- Full Text
- View/download PDF
44. Bubbling fluidised bed gasification of wheat straw-gasifier performance using mullite as bed material
- Author
-
Phil Hemmingway, Seán T. Mac an Bhaird, Kevin McDonnell, Sergio C. Capareda, Eilín Walsh, and Amado L. Maglinao
- Subjects
Standard conditions for temperature and pressure ,Bubbling fluidised bed ,Wood gas generator ,Waste management ,Heating value ,General Chemical Engineering ,Distributor ,Producer gas ,General Chemistry ,Wheat straw ,Combustion ,Isothermal process ,Mullite ,Environmental science ,Heat of combustion ,Gas composition ,Gasification - Abstract
The adoption of wheat straw as a fuel for gasification processes has been hindered due to a lack of experience and its propensity to cause bed agglomeration in fluidised bed gasifiers. In this study wheat straw was gasified in a small scale, air blown bubbling fluidised bed using mullite as bed material. The gasifier was successfully operated and isothermal bed conditions maintained at temperatures up to 750 ◦C. Below this temperature, the gasifier was operated at equivalence ratios from 0.1 to 0.26. The maximum lower heating value of the producer gas was approximately 3.6 MJm−3 at standard temperature and pressure (STP) conditions and was obtained at an equivalence ratio of 0.165. In general, a producer gas with a lower heating value of approximately 3 MJm−3 at STP could be obtained across the entire range of equivalence ratios operated. The lower heating value tended to fluctuate, however, and it was considered more appropriate for use in heat applications than as a fuel for internal combustion engines. The concentration of combustibles in the producer gas was lower than that obtained from the gasification of wheat straw in a dual distributor type gasifier and a circulating fluidised bed. These differences were associated with reactor design and, in the case of the circulating fluidised bed, with higher temperatures. Equilibrium modelling at adiabatic conditions, which provides the maximum performance of the system, showed that the gasifier was operating at suboptimal equivalence ratios to achieve greatest efficiencies. The maximum calculated theoretical cold gas efficiency of 73% was obtained at an equivalence ratio of 0.35. Science Foundation Ireland Charles Parsons Energy Research Award Department of Communications, Energy and Natural Resources of the Government of Ireland
- Published
- 2015
45. Controlling moisture content and truck configuration to optimise biomass supply chains in Ireland
- Author
-
Ger Devlin, Amanda Sosa, Kevin McDonnell, and Mauricio Acuna
- Subjects
Truck ,Moisture content ,Engineering ,Power station ,Waste management ,Payload efficiency ,business.industry ,Biomass supply chain ,Mechanical Engineering ,Supply chain ,Truck configuration ,Biomass ,Haulage ,Building and Construction ,Agricultural engineering ,Management, Monitoring, Policy and Law ,Renewable energy ,Cost reduction ,General Energy ,Logistics planning ,Energy supply ,business - Abstract
In the coming years, Ireland will continue to face an increasing demand for wood biomass as a renewable source of energy. This will result in strained supply/demand scenarios, which will call for new planning and logistics systems capable of optimizing the efficient use of the biomass resources. In this study, a linear programming tool was developed which includes moisture content (MC) as a driving factor for the cost optimisation of two supply chains that use short wood and whole trees from thinnings as material feedstock. The tool was designed and implemented to analyse the impact of moisture content and truck configurations (5-axle and 6-axle trucks) on supply chain costs and spatial distribution of the supply materials. The results indicate that the inclusion of wood chips from whole trees reduces the costs of wood energy supply in comparison with only producing wood chips from short wood to satisfy the demand, with 9.8% and 10.2% cost reduction when transported with 5-axle and 6-axle trucks respectively. Constraining the MC of the wood chips delivered to the power plant increases both transport and overall supply chain costs, due, firstly to an increase in the haulage distance and secondly, to the number of counties providing the biomass material. In terms of truck configuration, the use of 6-axle trucks resulted in a 14.8% reduction in the number of truckloads and a 12.3% reduction in haulage costs in comparison to the use of 5-axle trucks across the MC scenarios analysed. Science Foundation Ireland CoFoRD (National Council for Forest Research and Development in Ireland) Charles Parsons Energy Research Program
- Published
- 2015
46. Combining Wind and Pumped Hydro Energy Storage for Renewable Energy Generation in Ireland
- Author
-
Eilín Walsh, Kevin McDonnell, Patrick J. Solan, and Alice Coburn
- Subjects
Pumped-storage hydroelectricity ,Engineering ,Renewable energy ,EU Habitats Directive ,Wind power ,Power station ,Pumped hydro energy storage ,business.industry ,Environmental engineering ,EU Birds Directive ,Offshore wind power ,Energy development ,Intermittent energy source ,business ,Feed-in tariff ,Wind energy ,Ireland - Abstract
Ireland has one of the highest wind energy potentials in Europe. The intermittent nature of wind makes this renewable resource impractical as a sole source of energy. Combining wind energy with pumped hydro energy storage (PHES) can overcome this intermittency, consuming energy during low-demand periods and supplying energy for periods of high demand. Currently Ireland has a number of hydroelectric power plants and wind farms of various scales in operation. A feasibility study was conducted to investigate the potential of securing a reliable source of renewable energy by increasing the penetration of hydroelectric power by means of combined wind-PHES developments. The greatest wind potential is experienced along the western coast of Ireland and a number of sites were identified here which satisfied a minimum mean wind speed criterion of 10.5 ms−1. Each site was then further evaluated according to topographical requirements for PHES. All but two of the identified sites are immediately unsuitable due to the presence of areas protected under European legislation; this highlights the nonenergy related obstacles in the path of renewable energy generation in Ireland and suggests that a compromise should be researched which could facilitate both renewable energy generation and species and habitat protection in Europe.
- Published
- 2014
47. Energy and economic implications of anaerobic digestion pasteurisation regulations in Ireland
- Author
-
Eilín Walsh, Kevin McDonnell, and James Coultry
- Subjects
Engineering ,Waste management ,business.industry ,Mechanical Engineering ,Energy balance ,Pasteurization ,Building and Construction ,Raw material ,Pollution ,Industrial and Manufacturing Engineering ,Alternative treatment ,law.invention ,Pasteurisation ,Anaerobic digestion ,General Energy ,law ,EU legislation ,Escherichia coli ,Electrical and Electronic Engineering ,National standard ,business ,Civil and Structural Engineering - Abstract
The use of anaerobic digestion for the treatment of organic wastes is spreading throughout Europe. A number of restrictions on organic wastes which can be treated in anaerobic digestion facilities and the subsequent handling of the digested material are specified in European legislation. Regulation 1774/2002/EC as amended states that after reduction the material must be heated to either 70 °C or 90 °C for a minimum of 60 min. An alternative Irish national standard of 60 °C for 48 h twice has been introduced in place of the EU standard. Anaerobic digestion systems are successful only if they produce a significant energy output. The aim of this research was therefore to examine both the EU and Irish national standards as well as a number of alternative treatment scenarios to determine their respective pasteurisation efficiency and energetic requirement. Post-digestion pasteurisation above 60 °C was found to satisfactorily remove all viable Escherichia coli bacteria from the test feedstock. It was determined that the most energy and economically efficient heat treatments were 60 °C for 1 h, 70 °C for 1 h (EU standard), and 80 °C for 30 min. The Irish national standard was found to be prohibitively energy inefficient and expensive.
- Published
- 2013
48. Fluidised bed pyrolysis of lignocellulosic biomasses and comparison of bio-oil and micropyrolyser pyrolysate by GC/M-FID
- Author
-
Eoin Butler, Dietrich Meier, Ger Devlin, and Kevin McDonnell
- Subjects
biology ,Waste management ,Moisture ,Chemistry ,Biomass ,Picea abies ,Ash ,Miscanthus ,Straw ,Secondary reactions ,biology.organism_classification ,Analytical Chemistry ,chemistry.chemical_compound ,Fuel Technology ,Biofuel ,Environmental chemistry ,Lignin ,Char ,Fluidised bed ,Pyrolysis - Abstract
The fast pyrolysis of spruce (Picea abies), short rotation willow coppice (Salix alba), Miscanthus (Miscanthus x giganteus), and wheat straw (Triticum aestivum) was compared on a laboratory scale bubbling fluidized bed reactor at 460–475 °C. The presence of ash, ranging from 0.26 wt.% for spruce to 3.76 wt.% for wheat straw (moisture free basis) favoured decomposition of cell-wall constituents to char (spruce [11.4 wt.%] < Salix [16.2 wt.%] < Miscanthus [21.8 wt.%] < wheat straw [21.5 wt.%]) with a reduction of liquid organic product (spruce [53.8 wt.%] > Salix [45.4 wt.%] > Miscanthus [37.3 wt.%] > wheat straw [37.2 wt.%]). Bio-oils from Miscanthus and wheat straw were inhomogeneous. Differences between absolute masses of compounds determined by GC/MS-FID of the bio-oils compared with Py-GC/MS-FID suggested a greater role of secondary reactions at the fluidised bed scale, with reduced concentrations of certain lignin-derived, furan and pyran compounds. Science Foundation Ireland Charles Parsons Energy Research Program
- Published
- 2013
49. Miscanthus production and processing in Ireland: An analysis of energy requirements and environmental impacts
- Author
-
Ger Devlin, Fionnuala Murphy, and Kevin McDonnell
- Subjects
Engineering ,Briquette ,Energy demand ,biology ,Biosolids ,Renewable Energy, Sustainability and the Environment ,business.industry ,Environmental engineering ,Biomass ,Miscanthus ,biology.organism_classification ,Miscanthus sinensis×giganteus ,Renewable energy ,Life cycle assessment ,Bioenergy ,Greenhouse gas ,Greenhouse gas emissions ,business ,Life-cycle assessment ,Miscanthus sinensisXgiganteus - Abstract
The environmental impact of bioenergy supply systems can be determined using life cycle assessment methodologies. This study focuses on the impact of production of Miscanthus pellets and briquettes, potentially used to satisfy renewable energy requirements in Ireland. The impact categories considered are particularly important when assessing bioenergy systems; global warming potential, acidification potential, eutrophication potential, and energy demand. The scope of the study incorporates Miscanthus cultivation, harvest, processing and transport to a biomass distributor. The aim of the research is to evaluate the effects of changes in keys variables on the overall environmental impacts of the system. The scenarios examined include replacement of synthetic fertilisers with biosolids, Miscanthus processing by pelleting and briquetting, and transport distances of 50 and 100 km. Results indicate that maintenance and processing of the Miscanthus crop have the most environmental impacts with transport having less of an effect. Replacing synthetic fertiliser with biosolids results in a reduction in global warming potential of 23–33% and energy demand of 12–18%, but raises both acidification and eutrophication potential by 290–400% and 258–300%, respectively. Pelleting of Miscanthus requires more energy than briquetting, hence has higher impacts in each category assessed. Increasing the transport distance from 50 to 100 km, results in a small increase in each impact category. Miscanthus briquette production compares favourably with wood pellet, kerosene, and coal production, with Miscanthus pelleting proving more environmentally damaging. Science Foundation Ireland Charles Parsons Energy Research Program Author has checked copyright
- Published
- 2013
50. Fuel efficiency and CO2 emissions of biomass based haulage in Ireland - A case study
- Author
-
Ger Devlin, Kevin McDonnell, and Radomir Klvac
- Subjects
Truck ,Engineering ,Waste management ,business.industry ,Litre/ton ,Mechanical Engineering ,Biomass haulage ,Environmental engineering ,Biomass ,Haulage ,Building and Construction ,CO2 emissions ,Pollution ,Industrial and Manufacturing Engineering ,Tonnage ,Litre/km ,Axle ,Diesel fuel ,General Energy ,Fuel efficiency ,Electrical and Electronic Engineering ,business ,Civil and Structural Engineering ,Fleet management - Abstract
The purpose of this study was to analyse how biomass based haulage in Ireland performed as a measure of efficiency under 4 main criteria; distance travelled, fuel consumption, fuel consumption per unit of biomass hauled and diesel CO2 emissions. The applicability of truck engine diagnostic equipment was tested to analyse the schedule of engine data that could be recorded in real-time from a 5 axle articulated biomass truck. This identified how new on board truck technology in Ireland could be used to monitor data in real-time, specifically fuel consumption, litre/km, litre/ton and distance to allow for informed analysis of how efficient new biomass trucking operations currently are in Ireland. Fleet Management System (FMS) monitoring systems are a relatively new technology in biomass and log transport in Ireland. They are more common place in the food supply chain with refrigerated units travelling across continental Europe where food temperature and truck movements are controlled data from a central dispatch. A GPS asset tracking monitoring system was also installed on the truck over the test period to record trip log data. The BT (biomass truck) was a 5 axle, 2004 DAF XF Euro III 430hp 4*2. Initial results showed that for the BT, the average daily fuel consumption varied from 0.23 L/km to 0.47 L/km. The thresholds of travelled distance were between 20.92 km and 434.91 km respectively with average fuel consumption per tonnage of woodchips of 0.16 L/ton and 5.68 L/ton. When the total daily distance is limited to 1 load within 200 km roundtrip versus 1 load at approximately 400 km trip, the % difference in logistic cost (€/T) is 56%. Delivering 2 loads per 400 km trip shows a 5.4% decrease in logistic costs versus the Trip 1 scenario confirming the increased efficiency of a more localised transport approach. A maximum percentage difference in costs of 45% that exists between a 2 load and 1 load trip occurs for Trip 22 and Trip 5 but this increases to 72% when analysing for 2 load versus 1 load for distances over 400 km. Trip 7 and 12 are both below 50 km and seem to be the exception and to compare could possibly show an element of distortion. The closest logistic cost to Trip 12 is Trip 5 with 113% higher costs confirming how a 50 km roundtrip can impact significantly on lowering biomass transport costs. Science Foundation Ireland Charles Parsons Energy Research Programme
- Published
- 2013
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