Digital Commons Network^™

Constructive Dialogue: Beps And The Tcja., Reuven Avi-Yonah

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From its inception, the international tax regime was heavily influenced by the United States. The regime is traditionally traced back to the work of the four economists for the League of Nations in 1923, who came up with the orig- inal compromise underlying the tax treaty network, i.e., that passive income should be taxed primarily at residence and active income primarily at source (the “benefits principle”). Arguably, this compromise between the claims of res- idence and source countries was made possible by the U.S. unilateral adoption of the foreign tax credit in 1918, because the United States (already the world’s …

Epilogue: The Need For A New And Critical Democracy, William J. Novak, Stephen W. Sawyer

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Democratic critiques of neoliberalism have been comparatively rare, and positive democratic rejoinders to the social and political ruins of neoliberalism have been rarer. The question thus presents itself – what would an overtly democratic critique of neoliberalism look like and, beyond critique, what would a constructive democratic response to neoliberalism entail?

Bioactive Indanes: Development And Validation Of An Lc-Ms/Ms Bioanalytical Method For The Determination Of Ph46a, A New Potential Anti-Inflammatory Agent, In Dog And Rat Plasma And Its Application To A Pharmacokinetic Study In Dog, Gaia Scalabrino, Tao Zhang, Neil Frankish, Helen Sheridan

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A new chemical entity, which is a chiral indane dimer, PH46A, has been developed by our research group. As a clinical candidate. PH46A has recently completed Phase I clinical studies in man. Previously, during its pre-clinical development, in in vivo pre-clinical studies PH46A showed potent anti-inflammatory properties, which can be targeted at a range of diseases, including inflammatory bowel disease (IBD). To support the pre-clinical development of this drug candidate, we developed a LC MS/MS method for determining PH46 (the acid form of PH46A salt) in both dog and rat plasma using Compound 1 as internal standard (IS). Those species …

Bioactive Indanes: Insight Into The Bioactivity Of Iindane Dimers Related To The Lead Anti‐Inflammatory Molecule Ph46a, Kit Chan, Neil Frankish, Tao Zhang, Abdulilah Ece, Aoife Cannon, Jacintha O’Sullivan, Helen Sheridan

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Objectives PH46A (1) demonstrates significant anti-inflammatory activity in phenotypic models but its mechanism and site of action have been elusive. Current study focused on the bioactivity of PH46 (2) and related novel indane dimers (6-10) to investigate the impact of changes in substitution and stereochemistry at the C-1 and C-2 positions of the PH46 (2) scaffold.

Methods Cytotoxicity profiles of compounds were established using THP-1 macrophages and SW480 cells. Effects of the compounds were then evaluated at 10 μM using 5-lipoxygenase (LOX) and 15-LOX enzymes, and 5-LOX binding was evaluated in silico against NDGA, nitric oxide (NO) released from LPS-induced …

Bioactive Indanes: Proof Of Concept Study For Enantioselective Synthetic Routes To Ph46a, A New Potential Anti-Inflammation Agent, Tao Zhang, Gaia Scalabrino, Neil Frankish, Helen Sheridan

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PH46A is a single enantiomer and a member of the 1,2-indane dimer family. It has two contiguous stereogenic centers with S,S configurations, one of which being a quaternary center, which has been developed as a clinical candidate for the treatment of inflammatory and autoimmune conditions. The current synthetic route to PH46A involves the generation of an unwanted enantiomer (R,R)-7, thus reducing the final yield significantly. Therefore, we have investigated potential alternatives to improve the efficiency of this synthesis. The first phase of the study has demonstrated proof of principle for a chiral alkylation of ketone 3 using phase-transfer …

Investigation Of The Stereoselective Synthesis Of The Indane Dimer Ph46a, A New Potential Anti-Inflammatory Agent, Graham R. Cumming, Tao Zhang, Gaia Scalabrino, Neil Frankish, Helen Sheridan

Articles

PH46A, belonging to a class of 1,2-Indane dimers, has been developed by our research group as a potential therapeutic agent for the treatment of inflammatory and autoimmune diseases. The initial synthetic route to PH46A gave a low overall yield, due in large part to the generation of undesired diastereoisomer 5 and the unwanted enantiomer (R,R)-8 during the synthesis. The aim of this work was to carry out a comprehensive investigation into the stereoselective synthesis of PH46A. Significant progress was made on the ketone reduction step, where the use of triisobutylaluminum [TiBA, Al(iBu)₃] afforded high selectivity for …

From Nature To Medicinal Chemistry: Anti-Cancer Activity Of Novel Indane Scaffolds, Tao Zhang, Vilmar Bandero-Filho, Kit Chan, Lorraine O’Driscoll, Neil Frankish, Helen Sheridan

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No abstract provided.

Drug Discovery: Novel Indane Scaffolds With Anticancer Activity, Vilmar Bandero, Tao Zhang, Kit Chan, Lorraine O’Driscoll, Claire Corcoran, Neil Frankish, Helen Sheridan

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No abstract provided.

Novel Mast Cell-Stabilising Amine Derivatives Of 3,4 Dihydronaphthalen-1(2h)-One And 6,7,8,9-Tetrahydro-5h-Benzo[7]Annulen-5-One, James W. Barlow, Tao Zhang, Orla Woods, Adam J. Byrne, John J. Walsh

Articles

In an investigation of 4-amino-3,4-dihydronaphthalen-1(2H)-ones as novel modulators of allergic and inflammatory phenomena, we have investigated a series of cyclic analogues. Tertiary amines of structural types 9, 10, 20 and 21 were synthesised and evaluated for mast cell stabilising activity. In vitro and in vivo studies showed that of these compounds, the cyclohexenylamino derivatives of tetralone and benzosuberone of series 20 and 21 exhibited interesting activity both in vitro and in vivo.

(1s)-1-Phenylethanaminium 4-{[(1s,2s)-1-Hydroxy-2,3-Dihydro-1h,1'H-[2,2'-Biinden]-2-Yl]Methyl}Benzoate, Christopher S. Frampton, Tao Zhang, Gaia A. Scalabrino, Neil Frankish, Helen Sheridan

Articles

The title molecular salt, C(8)H(12)N(+)·C(26)H(21)O(3)(-), contains a dimeric indane pharmacophore that demonstrates potent anti-inflammatory activity. The indane group of the anion exhibits some disorder about the α-C atom, which appears common to many structures containing this group. A model to account for the slight disorder was attempted, but this was deemed unsuccessful because applying bond-length constraints to all the bonds about the α-C atom led to instability in the refinement. The absolute configuration was determined crystallographically as S,S,S by anomalous dispersion methods with reference to both the Flack parameter and Bayesian statistics on Bijvoet differences. The configuration was also determined …

N-Cyclo­Pentyl-N-(3-Oxo-2,3-Dihydro-1h-Inden-1-Yl)Acetamide, Tao Zhang, Tom Mccabe, Bartosz Marzec, Neil Frankish, Helen Sheridan

Articles

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

2-(Di­Phenyl­Methyl­Idene)-2,3-Di­Hydro-1h-Inden-1-One, Tao Zhang, Vilmar Bandero, Tom Mccabe, Neil Frankish, Helen Sheridan

Articles

In the title mol­ecule, C₂₂H₁₆O, the indanone ring system is approximately planar with a dihedral angle between the fused rings of 5.13 (14)°. Two benzene rings are linked together at one side of a double bond, sitting on either side of the indanone ring system and making dihedral angles of 70.30 (12) and 44.74 (13)° with it. In the crystal, hydrogen bonding is not present, but weak C—H⋯π or π–π inter­actions occur and mol­ecules form a sheet-like structure in the bc plane.

Molecular Structure Studies Of (1s,2s)-2-Benzyl-2,3-Dihydro-2-(1hinden- 2-Yl)-1h-Inden-1-Ol, Tao Zhang, Krzysztof Paluch, Gaia Scalabrino, Neil Frankish, Anne-Marie Healy, Helen Sheridan

Articles

The single enantiomer (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol (2), has recently been synthesized and isolated from its corresponding diastereoisomer (1). The molecular and crystal structures of this novel compound have been fully analyzed. The relative and absolute configurations have been determined by using a combination of analytical tools including X-ray crystallography, X-ray Powder Diffraction (XRPD) analysis and Nuclear Magnetic Resonance (NMR) spectroscopy.

Mast Cell Stabilisers, Tao Zhang, Deirdre Frances Finn, James William Barlow, John Jarlath Walsh

Articles

Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic rhinitis, conjunctivitis, asthma, psoriasis, mastocytosis and the progression of many different cancers. Thus, there is intense interest in the development of agents which prevent mast cell mediator release or which inhibit the actions of such mediators once released into the environment of the cell. Much progress into the design of new agents has been made since the initial discovery of the mast cell stabilising properties of khellin from Ammi visnaga and the clinical approval of cromolyn sodium. …

Antidiabetic Activities Of An Lc/Ms Fingerprinted Aqueous Extract Of Fagonia Cretica L. In Preclinical Models, Imran Nazir, Nisar Ur Rahman, Zunaira Alvi, M. Hafizur Rahman, Jandirk Jandirk Sendker, Tao Zhang, Neil Frankish, Helen Sheridan

Articles

Diabetes mellitus is a chronic disease and one of the most important public health challenges facing mankind. Fagonia cretica is a medicinal plant used widely in the Punjab in Pakistan. A recent survey has demonstrated that traditional healers and herbalists frequently use this plant to treat diabetes. In the current study, the traditional medicine was prepared as a tea, and the profile of the main metabolites present in the traditional medicine was analysed via LC/MS/MS. The extract was shown to contain a number of phenolic glycosides including quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, kaempferol-3-O-glycoside, kaempferol-3(6′-malonylglucoside), isorhamnetin-3-O-rutinoside, and isorhamnetin 3-(6″-malonylglucoside) in addition to two unidentified …

Assessing The Biological Safety Of Atmospheric Cold Plasmatreated Wheat Using Cell And Insect Models, Agata Los, Dana Ziuzina, Daniela Boehn, Paula Bourke

Articles

Atmospheric cold plasma (ACP) is under investigation for an extensive range of biocontrol applications in food biosystems. However, the development of a novel intervention technology requires a thorough evaluation of the potential for negative effects and the implications for the human and animal food chains’ safety. The evaluations were performed using a contained, high-voltage, dielectric barrier discharge plasma system. The cytotoxicity of two types of food models—a liquid model (wheat model medium (WMM)) vs. a solid model (wheat grain extract (WGE)) was compared in vitro using the mammalian cell line CHO-K1. The residual toxicity of ACP treatment of grains for …

Characterization Of Antimicrobial Effects Of Plasma-Treated Water (Ptw) Produced By Microwave-Induced Plasma (Midiplexc) On Pseudomonas Fluorescens Biofilms, Oliver Handorf, Viktoria Isabella Pauker, Thomas Weihe, Eric Freund, Sander Bekeschus, Katharina Riedel, Uta Schnabel, Jörg Ehlbeck

Articles

stract: For the decontamination of surfaces in the food production industry, plasma generated compounds (PGCs) such as plasma-treated water (PTW) or plasma processed air (PPA) offer many promising possibilities for future applications. Therefore, the antimicrobial effect of water treated with microwave-induced plasma (MidiPLexc) on Pseudomonas fluorescensbiofilms was investigated. 10 ml deionized water was treated with the MidiPLexc plasma source for 100 s, 300 s and 900 s (pre-treatment time) and the bacterial biofilms were exposed to the PTW for 1 min, 3 min and 5 min (post treatment time). To investigate the influence of PTW on P. fluorescensbiofilms, microbiological assays …

Cold Atmospheric Plasma Induces Silver Nanoparticle Uptake, Oxidative Dissolution And Enhanced Cytotoxicity In Glioblastoma Multiforme Cells, Eline Manaloto, Aoife Gowen, Anna Lesniak, Zhonglei He, Alan Casey, Patrick J. Cullen, James Curtin

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Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5 mA, duty cycle of 7.5kVA and input frequency of 50–60Hz) and 10 nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in …

Computational Modelling Approach For The Optimization Of Apple Juice Clarification Using Immobilized Pectinase And Xylanase Enzymes, Shady Hassan, Gwilym Williams, Amit Jaiswal

Articles

Apple juice is typically marketed as a clear juice, and hence enzymatic treatments are common practices in juice industry. However, enzymatic treatments have been shown to face some challenges when process efficiency, and cost effectiveness are concerned. Therefore, it is necessary to optimize the enzymatic treatment process to maximize efficiency, and reuse enzymes to minimize the overall cost via immobilization. In this context, the present work features the immobilization of pectinase and xylanase from M. hiemalis on genipin-activated alginate beads, with subsequent evaluation of its efficacy in apple juice clarification. A central composite rotatable design (CCRD), coupled with artificial neural …

Effect Of Atmospheric Cold Plasma On The Functional Properties Of Whole Wheat (Triticum Aestivum L.) Grain And Wheat Flour, Sonal Chaple, Chaitanya Sarangapani, John B. Jones, Ed Carey, Lucie Causeret, Annaik Genson, Brendan Duffy, Paula Bourke

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Atmospheric cold plasma (ACP) has emerged as a novel processing technology, with demonstrated efficiencies in microbial inactivation. However, studies on the effects of ACP and potential to modify the functional properties of foods are sparse. The objective of this study is to determine the effect of ACP on physico-chemical and functional properties of wheat flour. In this study, both whole wheat grains and wheat flour were subjected to a dielectric barrier discharge (DBD) contained plasma reactor for a range of treatment times (5–30 min) at 80 kV. Plasma treatment increased the flour hydration properties of wheat flour. Rapid visco-analyser results …

Effects Of Cold Atmospheric Plasma On Mackerel Lipid And Protein Oxidation During Storage, Juan M. Pérez-Andrés, María De Alba, Sabine M Harrison, Nigel P. Brunton, Patrick J. Cullen, Brijesh K. Tiwari

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The present study investigated the effects of cold atmospheric plasma on the shelf-life stability of lipids andproteins of commercially packaged mackerelfillets. The results showed no significant effects on lipid oxidationbetween the control samples and those treated at 80 kV for extended treatment times of 5 min using an in-package plasma system. In addition, no significant changes (p > 0.05) were found in the fatty acid compositionor nutritional quality indices after treatment. Finally, the formation of carbonyls was accelerated by plasmatreatment at the end of the storage period for 4 °C and 8 °C. These results suggest that cold atmospheric plasmatechnologies are …

Effects Of Cold Plasma On Wheat Grain Microbiome And Antimicrobial Efficacy Against Challenge Pathogens And Their Resistance, Agata Los, Dana Ziuzina, Daniela Boehm, Paula Bourke

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The safety and quality of cereal grain supplies are adversely impacted by microbiological contamination, with novel interventions required to maximise whole grains safety and stability. The microbiological contaminants of wheat grains and the efficacy of Atmospheric Cold Plasma (ACP) for potential to control these risks were investigated. The evaluations were performed using a contained reactor dielectric barrier discharge (DBD) system; samples were treated for 0–20 min using direct and indirect plasma exposure. Amplicon-based metagenomic analysis using bacterial 16S rRNA gene and fungal 18S rRNA gene with internal transcribed spacer (ITS) region was performed to characterize the change in microbial community …

Food Security And Diet Quality In Native Hawaiian, Pacific Islander, And Filipino Infants 3 To 12 Months Of Age, Sally Campbell, John J. Chen, Carol J. Boushey, Heather Eicher-Miller, Fengqing Zhu, Marie K. Fialkowski

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Food insecurity and other nutritional risks in infancy pose a lifelong risk to wellbeing; however, their effect on diet quality in Native Hawaiian, Pacific Islander, and Filipino (NHPIF) infants in Hawai‘i is unknown. In this cross-sectional analysis, the association between various indicators of food security and NHPIF infant diet quality were investigated in 70 NHPIF infants aged 3–12 months residing on O‘ahu, Hawai‘i. The dietary assessments of the infants were collected using a mobile food record^TM. Foods consumed across four days were categorized into seven food groups. Indicators for food security were examined through an adapted infant food …

Temperature Stability And Effectiveness Of Plasma-Activated Liquids Over An 18 Months Period, Evanthia Tsoukou, Paula Bourke, Daniela Boehm

Articles

Non-buffered plasma-activated liquids such as water and saline have shown bactericidal effects. In the present study, we investigated the anti-bacterial efficacy and stability of plasma-activated water (PAW) and plasma-activated saline (PAS), generated using a high voltage dielectric barrier discharge system. This study compares the potential of non-buffered plasma-activated liquids (PAL) for the inactivation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) after storage of the solutions at five different temperatures for a storage time up to 18 months after their generation. The temperatures used were room temperature, 4 °C, −16 °C, −80 °C, −150 °C. Both PAW and …

Development Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves, Ahmed Al-Sabi, Declan Daly, Myles Rooney, Cian Hughes, Gemma K. Kinsella, Seshu Kaza, Kieran Nolan, J. Oliver Dolly

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Members of the voltage-gated K+ channel subfamily (Kv1), involved in regulating transmission between neurons or to muscles, are associated with human diseases and, thus, putative targets for neurotherapeutics. This applies especially to those containing Kv1.1 α subunits which become prevalent in murine demyelinated axons and appear abnormally at inter-nodes, underlying the perturbed propagation of nerve signals. To overcome this dysfunction, akin to the consequential debilitation in multiple sclerosis (MS), small inhibitors were sought that are selective for the culpable hyper-polarising K+ currents. Herein, we report a new semi-podand – compound 3 – that was designed based on the modelling of …

Elemental Analysis Of Fish Feed By Laser-Induced Breakdown Spectroscopy, Md. Ashraful Alam, Camille Pasquet, Fintan Moran, Patrick J. Cullen, Carl Sullivan, Maria Casado-Gavalda, Maria Markiewicz-Keszycka

Articles

In this study, the potential of laser-induced breakdown spectroscopy (LIBS) as an efficient multi-elemental quantification tool for fish feed is determined. A particular focus of this paper is total chromium, an essential element that has the potential to be toxic and carcinogenic. In total six elements, four macro-elements (Ca, Fe, K and Mg) and two micro-elements (Cr and Rb), were modelled using LIBS spectra of aquafeed samples. Reference analysis was conducted via inductively coupled plasma mass spectrometry (ICP-MS) and showed good agreement with LIBS predictions. These results provide evidence that LIBS has the potential to be utilized in the field …

Prediction Of Warner-Bratzler Shear Force, Intramuscular Fat, Drip-Loss And Cook-Loss In Beef Via Raman Spectroscopy And Chemometrics, Raquel Cama-Moncunill, Jamie Cafferky, Caroline Augier, Torres Sweeney, Paul Allen, Alessandro Ferragina, Carl Sullivan, Andrew Cromie, Ruth Hamill

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Rapid prediction of beef quality remains a challenge for meat processors. This study evaluated the potential of Raman spectroscopy followed by chemometrics for prediction of Warner-Bratzler shear force (WBSF), intramuscular fat (IMF), ultimate pH, drip-loss and cook-loss. PLS regression models were developed based on spectra recorded on frozen-thawed day 2 longissimus thoracis et lumborum muscle and validated using test sets randomly selected 3 times. With the exception of ultimate pH, models presented notable performance in calibration (R2 ranging from 0.5 to 0.9; low RMSEC) and, despite variability in the results, promising predictive ability: WBSF (RMSEP ranging from 4.6 to 9 …

Design, Synthesis, And Biological Evaluation Of Aryl Piperazines With Potential As Antidiabetic Agents Via The Stimulation Of Glucose Uptake And Inhibition Of Nadh:Ubiquinone Oxidoreductase, R. Devine, M. Kelada, S. Leonard, D.S.D. Martin, J.M.D. Walsh, C.J. Breen, R.B. Driver, Gemma K. Kinsella, J.B.C Findlay, J.C. Stephens

Articles

The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose …

In Situ Image Processing And Data Binning Strategy For Particle Engineering Applications, Toufic El Arnaout, Patrick J. Cullen

Articles

Crystallization control can be improved through real-time monitoring technologies. Here, a workflow is demonstrated on rapid batch cooling crystallization of L-glutamic acid. First, in situ images were generated using video microscopy sensors and analyzed, by employing a single, rapid macro code to extract particle data descriptors. A binning procedure (over time) was performed, where every data point represented the counts of particles within a specific size or shape range per 100 images. This binning method was found more informative in tracking of the populations compared to whole image averages or individual particle datapoints. This study provides a step-by-step guide towards …

Safety Evaluation Of Plasma-Treated Lettuce Broth Using In Vitro And In Vivo Toxicity Models, Caitlin Heslin, Daniela Boehm, Brendan F. Gilmore, Julianne Megaw, Paula Bourke

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Cold atmospheric plasma is a promising new non-thermal technology for improving the microbiological safety and shelf-life of food products, particularly fresh produce and minimally processed fruit and vegetables. Limited research has been conducted on the safety of plasma-treated foods for human or animal consumption. This study focuses on basic safety studies by investigating lettuce broth treated with a di-electric barrier discharge plasma device as a fresh produce model in terms of in vitro cytotoxic and mutagenic effects on mammalian cells and its in vivo toxicity on Galleria mellonella larvae. Low cytotoxic effects were detected in vitro and mutagenic events were …