Digital Commons Network^™

Comparison Of The Anticoagulant Response Of A Novel Fluorogenic Anti-Fxa Assay Wth Two Commercial Anti-Fxa Chromogenic Assays, Leanne F. Harris, Aoife O'Brien, Vanessa Castro-Lopez, James S. O'Donnell, Anthony J. Killard

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Introduction: Fast and accurate monitoring is crucial in the successful regulation of coagulation therapy. For the treatment of venous thromboembolism, both unfractionated heparin (UFH) and low molecular weight heparins (LMWH) are commonly administered. The chromogenic anti-factor Xa (FXa) assay is currently considered the ‘gold standard’ assay for monitoring LMWH. However different commercial chromogenic methods often differ when tested with the same samples. Fluorogenic anti-FXa assays have the potential to offer greater benefits over chromogenic assays in terms of greater specificity, sensitivity and they are not so influenced by sample opacity or turbidity. Materials and Methods: Commercial plasmas were spiked with …

Evaluation Of Activated Partial Thromboplastin Time (Aptt) Reagents For Application In Biomedical Diagnostic Device Development, Magdalena Dudek, Leanne F. Harris, Anthony J. Killard

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Introduction: The most commonly used test for monitoring heparin therapy is the activated partial thromboplastin time (aPTT). The response of available aPTT reagents to heparin varies significantly. The aim of this study was to highlight the differences between aPTT reagents stored in a dried format to select the most suitable formulations to be used for the development of point-of-care diagnostic devices used for monitoring of unfractionated heparin dose response. Methods: Ten reagents were analysed in terms of their performance in liquid and in dried form after storage for 24 h and 14 days. Performance was assessed by measurement of the …

Comparison Of A Novel Fluorogenic Anti-Fxa Assay With A Central Laboratory Chromogenic Anti-Fxa Assay For Measuring Lmwh Activity In Patient Plasmas, Leanne F. Harris, Vanessa Castro-Lopez, James S. O'Donnell, Anthony J. Killard

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Introduction: Low molecular weight heparins (LMWHs) are used worldwide for the treatment and prophylaxis of thromboembolic disorders. Routine laboratory tests are not required due to the predictable pharmacokinetics of LMWHs, with the exception of pregnant patients, children, patients with renal failure, morbid obesity, or advanced age. Anti-Factor Xa (anti-FXa) plasma levels are most often employed in the assessment and guidance of accurate dosing in these patient cohorts. Materials and methods: A LMWH calibration curve was generated using citrated human pooled plasma spiked with pharmacologically relevant concentrations (0–1 U/ml) of two low molecular weight heparins; enoxaparin and tinzaparin. Least squares analysis …

Bayesian Inference For Exponential Random Graph Models, Alberto Caimo, Nial Friel

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Exponential random graph models are extremely difficult models to handle from a statistical viewpoint, since their normalising constant, which depends on model parameters, is available only in very trivial cases. We show how inference can be carried out in a Bayesian framework using a MCMC algorithm, which circumvents the need to calculate the normalising constants. We use a population MCMC approach which accelerates convergence and improves mixing of the Markov chain. This approach improves performance with respect to the Monte Carlo maximum likelihood method of Geyer and Thompson (1992).

Now For The Science Bit: Implementing Community-Based Learning In Chemistry, Claire M. Mcdonnell, Patricia Ennis, Leslie Shoemaker

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Purpose – The purpose of this paper is to contribute to the understanding of student learning from community engagement by critically assessing the implementation of this pedagogical approach in the context of teaching and learning chemistry and also evaluating the role of personal development in student-community engagement.

Design/methodology/approach – A case study on the implementation since 2007 of community-based learning (also called service-learning) projects in an academic department in Ireland is presented. Analysis of assessment grades, student reflective accounts and evaluation questionnaires informs this work as does a recently completed self-assessment of our activities using Shumer’s Self-Assessment for Service Learning. …

Synthesis, Evaluation And Structural Studies Of Antiproliferative Tubulin-Targeting Azetidin-2-Ones, Niamh O'Boyle, Lisa M. Greene, Orla Bergin, Jean-Baptiste Fichet, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

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A series of azetidin-2-ones substituted at positions 2, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerization that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the …

Cracks In The Wall, A Bulge Under The Carpet: The Singular Story Of Religion, Evolution, And The U.S. Constitution, Susan Haack

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No abstract provided.

The Security Council As A Legal Hegemon, Daniel H. Joyner

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This article will examine the United Nations Security Council's efforts to implement preserve and universalize the obligations of the 1968 Nuclear Nonproliferation Treaty This discussion will lead to questions regarding the Security Council's role and authority in the international legal system and ultimately to a consideration of how the international legal system can better guarantee that the Security Council does not exercise an unwarranted degree of legal power at the expense of the member states of the United Nations

Recent Developments In The International Law Regarding Nuclear Weapons Current Developments: Public International Law, Daniel H. Joyner

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No abstract provided.

Introductory Note To The 2010 Strategic Arms Reduction Treaty, Daniel H. Joyner

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No abstract provided.

The Enforceability Of Exacted Conservation Easements, Jessica Owley

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No abstract provided.

Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

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The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC₅₀ value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …

The Implementation Of Pre-Lecture Resources To Reduce In-Class Cognitive Load: A Case Study For Higher Education Chemistry, Michael Seery, Roisin Donnelly

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This case study describes an effective method to ameliorate the cognitive load caused by new terminology and concepts in lectures. Ten online pre-lecture resources whose design was underpinned by the principles of cognitive load theory were provided to a class of 49 first year university level chemistry students. Each resource introduced a number of key concepts to the forthcoming lecture and included a quiz for students to test understandings and identify misconceptions. The evaluation of the implementation of resources was measured by considering the difference in exam marks for in-semester test and end of module exam. These showed that the …

Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan

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Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC₅₀ values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed …

Sequential Climate Change Policy, Edward A. Parson, Darshan Karwat

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Successfully managing global climate change will require a process of sequential, or iterative, decision‐making, whereby policies and other decisions are revised repeatedly over multiple decades in response to changes in scientific knowledge, technological capabilities, or other conditions. Sequential decisions are required by the combined presence of long lags and uncertainty in climate and energy systems. Climate decision studies have most often examined simple cases of sequential decisions, with two decision points at fixed times and initial uncertainties that are resolved at the second decision point. Studies using this formulation initially suggested that increasing uncertainty favors stronger immediate action, while the …

Quantification Of Unfractionated Heparin In Human Plasma And Whole Blood By Means Of Novel Fluorogenic Anti-Fxa Assays, Vanessa Castro-Lopez, Leanne F. Harris, James S. O'Donnell, Anthony J. Killard

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Novel and sensitive plate-based fluorogenic anti-factor Xa (FXa) assays were investigated to quantify unfractionated heparin (UFH) in human plasma and whole blood within the therapeutic ranges of 0–1.6 U/mL and 0–0.8 U/mL, respectively. Two fluorogenic anti-FXa assay methods were defined for low (0–0.6 U/mL) and high (0.6–1.2 U/mL) pharmacologically relevant UFH concentration ranges in pooled human plasma. In both cases significant differences were observed at intervals of 0.2 U/mL (P < 0.05). The semi-logarithmic plots of the calibration curves in the low and high UFH range were both fitted to linear regressions with correlation coefficients of 0.96 and >0.99, respectively. The assay was also optimized for whole blood which was capable of differentiating UFH concentrations at intervals of 0.2 U/mL (P < 0.05) in the range of 0–0.4 U/mL. The statistically different results were fitted to a linear regression with a correlation coefficient of >0.99. The results obtained in this study …

Modelling The Effect Of Asparaginase In Reducing Acrylamide Formation In Biscuits, Monica Anese, Barbara Quarta, Jesus Maria Frias

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The influence of asparaginase on acrylamide formation, as well as colour development, in short dough biscuits was studied. In particular, asparaginase concentration, incubation time and temperature were changed according to an experimental design. As acrylamide formation was found to vary significantly between biscuits obtained by using the same ingredients and process, a mixed effect model was used to model variation of acrylamide concentration. By contrast a fixed effect model was used for colour polynomial analysis. Within the range of study, the overall results allowed the best conditions for minimising acrylamide formation to be found. It can be suggested that acrylamide …

Application Of Principal Component And Hierarchical Cluster Analysis To Classify Different Spices Based On In Vitro Antioxidant Activity And Individual Polyphenolic Antioxidant Compounds, M. Hossain, A. Patras, Catherine Barry-Ryan, Ana Belen Martin-Diana, N. Brunton

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This study investigated the variations in antioxidant profiles between spices using pattern recognition tools; classification was achieved based on the results of global antioxidant activity assays (2,2-diphenyl-1-picrylhydrazyl [DPPH], oxygen radical absorbance capacity [ORAC], ferric reducing antioxidant power [FRAP], microsomal lipid peroxidation [MLP] and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) [ABTS]), levels of different polyphenolic compounds (gallic acid [GA], carnosol [CAR], carnosic acid [CRA], caffeic acid [CA], rosmarinic acid [RA], luteolin-7-O-glucoside [LOG], apigenin-7-O-glucoside [APOG] and total phenols [TP]) of spices namely rosemary, oregano, marjoram, sage, basil, thyme, fennel, celery, cumin and parsley, commonly consumed in Ireland were analyzed. Rosemary showed the highest antioxidant activity measured …

Phenolic Composition, Antioxidant Capacity And Antibacterial Activity Of Selected Irish Brassica Vegetables, Amit Jaiswal, Gaurav Rajauria, Nissreen Abu-Ghannam, Shilpi Gupta

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Vegetables belonging to the Brassicaceae family are rich in polyphenols, flavonoids and glucosinolates, and their hydrolysis products, which may have antibacterial, antioxidant and anticancer properties. In the present study, phenolic composition, antibacterial activity and antioxidant capacity of selected Brassica vegetables, including York cabbage, Brussels sprouts, broccoli and white cabbage were evaluated after extraction with aqueous methanol. Results obtained showed that York cabbage extract had the highest total phenolic content, which was 33.5, followed by 23.6, 20.4 and 18.4 mg GAE/g of dried weight (dw) of the extracts for broccoli, Brussels sprouts and white cabbage, respectively. All the vegetable extracts had …

Effect Of Different Drying Temperatures On The Moisture And Phytochemical Constituents Of Edible Irish Brown Seaweed, Shilpi Gupta, Sabrina Cox, Nissreen Abu-Ghannam

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The effect of different temperatures on the drying kinetics and the phytochemical constituents of edible Irish brown seaweed, Himanthalia elongata were studied. This kinetic study involved the modelling of the terms of Fick’s diffusion equation, for estimation of the diffusion coefficients. The diffusivity coefficient increased from 5.6×10−07-12.2×10−07 m2/s as the drying temperatures increased with an estimated activation energy of 37.2 kJ/mol. The experimental data was also fitted to different empirical kinetic models, Newton, Logarithmic and Henderson-Pabis, and the goodness of fit for the different models was evaluated. The effect of drying temperatures on the phytochemical constituents in seaweed was also …

The History Of Intellectual Property Taxation: Promoting Innovations And Other Intellectual Property Goals, Xuan-Thao Nguyen, Jeffrey A. Maine

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No abstract provided.

A Special Rule For Compound Protection For Dna-Sequences Impact Of The Ecj "Monsanto" Decision On Patent Practice, Jan B. Krauss, Toshiko Takenaka

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This article will analyze the Monsanto decision, and criticize the European Court of Justice's interpretation of Article 9 as being incomplete, in particular for failing to take account of all articles and recitals in the Biotech Directive relating to the scope of protection. It will argue that applying the concept of a function-limited protection is unnecessary if a claim directed to an isolated DNA sequence is properly interpreted. It will also discuss the possible impact not only on the protection scope but also on the patentability of gene patents.

Stranger Than Fiction: An "Inside" Look At Environmental Liability And Defense Strategy In The Deepwater Horizon Aftermath, William H. Rodgers, Jr., Jason Derosa, Sarah Reyneveld

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The Deepwater Horizon oil spill of April 20, 2010 initiated an environmental disaster that presented attorneys on both sides of the legal action with monumental challenges. Using the satirical format of a memo written by the corporate defense counsel to BP America four days after the spill began, this article investigates BP’s potential liability and strategic defense positions available in criminal and civil proceedings. Major federal environmental laws, including the Oil Pollution Act, the Clean Water Act and major wildlife protection statutes, are implicated by the Spill. The memo provides a clear picture of the existing opportunities for a responsible …

The Environmental Laws Of The 1970s: They Looked Good On Paper, William H. Rodgers, Jr.

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This article looks at the "top ten" environmental laws enacted in the 1970s, including the Clean Air Act, the Endangered Species Act, the National Environmental Policy Act, and the Resource Conservation and Recovery Act. It asks: What were the pin-up qualities that made these laws look good on paper? What were the features sponsors bragged about or critics deplored? How were they understood and described at the time of legislative birth? What was thought to be new, different, and better?

We know some of these things about all of these laws. I’ll exercise editorial judgment and declare four common features …

What Role For “Women,” “Men,” And Transpeople/Intersex People In Gender Equality: A Commentary, Edward D. Stein

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This has been a very rich opening panel to what promises to be a terrific conference. The panelists' comments go in such varied directions that it is a challenge to be both a commentator and summarizer, especially when I have just a few minutes to speak. What I plan to do is say a little bit to draw together some of the themes that the panelists have been talking about that are connected to a couple of topics I have been working on while at the same time trying to look forward to some of the things I hope we …

Protein Replacement Therapy Partially Corrects The Cholesterol-Storage Phenotype In A Mouse Model Of Niemann-Pict Type C2 Disease, Gitte Krogh Nielsen, Frederik Dagnaes-Hansen, Ida Elisabeth Holm, Steve Meaney, Derek Symula, Niels Trolle Andersen, Christian Wurtz Heegaard

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Niemann-Pick type C2 (NPC2) disease is a fatal autosomal recessive neurovisceral degenerative disorder characterized by late endosomal-lysosomal sequestration of low-density lipoprotein derived cholesterol. The breach in intracellular cholesterol homeostasis is caused by deficiency of functional NPC2, a soluble sterol binding protein targeted to the lysosomes by binding the mannose-6-phosphate receptor. As currently there is no effective treatment for the disorder, we have investigated the efficacy of NPC2 replacement therapy in a murine gene-trap model of NPC2-disease generated on the 129P2/OlaHsd genetic background. NPC2 was purified from bovine milk and its functional competence assured in NPC2-deficient fibroblasts using the specific cholesterol …

Legal Reasoning And Scientific Reasoning, Phoebe C. Ellsworth

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In my presentation for the 2010 Meador Lectures on Rationality, I chose to compare legal reasoning and scientific reasoning. Both law and science pride themselves on the rationality of their intellectual methods and believe that those methods are designed to analyze questions and reach the correct conclusions by means of reason, free from cognitive or emotional biases. Of course, both law and science often fall short of this ideal at all levels, from the decisions about individual legal cases or scientific studies to the acceptance of general theories. In many ways, the biases that mislead legal and scientific thinkers are …

In-Silico Hyperthermia Performance Of A Near-Field Patch Antenna At Various Positions On A Human Body Model, Sergio Curto, Terrence See, Patrick Mcevoy, Max Ammann, Zhi Ning Chen

Articles

A compact patch applicator designed to enhance targeted energy coupling at 434 MHz is a key enabler for sensitizing temperature increments in body regions containing superficial tumours. A detailed FDTD body model is used to explore simulated RF coupling and temperature increments for typical clinical conditions. The antenna impedance matching, specific absorption rate and thermal distribution parameters are evaluated to identify applied performance outcomes. The analysis reveals physiological-RF coupling patterns for an optimised closely-coupled single element applicator.

Evolutionary History And Spread Of Multidrug Resistant Inchi1 Plasmids In Salmonella Typhi, Kathryn Holt, Minh Duy Phan, Stephen Baker, Pham Thanh Duy, Tran Vu Thieu Nga, Satheesh Nair, Arthur Keith Turner, Ciara Walsh, Seamus Fanning, Sinead Farrell-Ward, Shanta Dutta, François-Xavier Weill, Julian Parkhill, Gordon Dougan, John Wain

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Typhoid fever, infection with Salmonella enterica serovar Typhi (S. Typhi), remains a serious health concern in many parts of the world, particularly where sanitation is poor. While vaccines against S. Typhi are available, coverage in endemic regions is low, leaving antimicrobial therapy central to disease control. Unfortunately, drug resistant S. Typhi emerged in the mid-1970s and multi-drug resistance (MDR) is now a significant problem in many typhoid endemic areas. In the S. Typhi population, MDR is almost exclusively conferred by self-transmissible IncHI1 plasmids carrying a suite of antimicrobial resistance genes. We compared eight IncHI1 plasmid sequences and identified single nucleotide …

Bioactive Potential And Possible Health Effects Of Edible Brown Seaweeds, Shilpi Gupta, Nissreen Abu-Ghannam

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Marine macroalgae (seaweeds) are rich in bioactive compounds that could potentially be exploited as functional ingredients for both human and animal health applications. Despite the intensive efforts that are being made to isolate and identify new compounds with potential medicinal, health or pharmaceutical activities, very few compounds with real potency are available. Bioactive compounds that are most extensively researched include sulfated polysaccharides, phlorotannins and diterpenes. These compounds have been reported to possess strong anti-viral, anti-tumor and anti-cancer properties. At the same time, the prebiotic health potential of the polysaccharides from seaweeds is also increasingly being studied either by feeding whole …