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Prediction Of Dna Damage And G2 Chromosomal Radio-Sensitivity Ex-Vivo In Peripheral Blood Mononuclear Cells With Label-Free Raman Microspectroscopy, Aidan Meade, Adrian Maguire, Jane Bryant, Daniel Cullen, Dinesh Medipally, Lisa White, Brendan Mcclean, Laura Shields, John Armstrong, Mary Dunne, Emma Noone, Shirley Bradshaw, Marie Finn, Aoife M. Shannon, Orla Howe, Fiona Lyng

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Liquid biopsies are a potentially rich store of biochemical information that can be linked to an individual’s response to therapeutic treatments, including radiotherapy, and which may ultimately play a role in the individualization of treatment regimens. Peripheral blood mononuclear cells (PBMCs) can be used for the biochemical profiling of the individual, but also, being living cells, can provide insights into the individuals response to ionizing radiation exposure.

Self-Processing Photopolymer Materials For Versatile Design And Fabrication Of Holographic Sensors And Interactive Holograms, Dervil Cody, Sabad-E Gul, Tatsiana Mikulchyk, Muhammad Irfan, Anastasia Kharchenko, Kamila Goldyn, Suzanne Martin, Svetlana Mintova, John Cassidy, Izabela Naydenova

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The aim of this paper is to discuss the benefits as well as the limitations of utilizing photopolymer materials in the design of holograms that are responsive to changes in their environment, such as changes in the concentration of a specific substance, temperature, and pressure. Three different case studies are presented, including both surface and volume phase holograms, in order to demonstrate the flexibility in the approach of utilizing holographic photopolymers for the design of sensors and interactive optical devices. First, a functionalized surface relief hologram is demonstrated to operate as an optical sensor for the detection of metal ions …

A Physical Biology, The Electron Neutrino Mass, And The Role Of Quantum Mechanics In Nature, Maurice Goodman

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In science we need to remove physics and earth science from the fundamental sciences and treat Biology as a fundamental natural (physical) science. Attempts to keep Biology autonomous because it is holistic, from the physical sciences, are just disguised anthropocentrism. Physical sciences have holistic features also. The autonomy of Biology is at odds with a holistic, integrated, science and is preventing progress in science. For example, every cell needs a 'global' communication system to keep order and stability with rapid information transfer across cellular scales. We have yet to figure out how this is achieved. Over the last 30 years, …

Enabling Quantification Of Protein Concentration In Human Serum Biopsies Using Attenuated Total Reflectance – Fourier Transform Infrared (Atr-Ftir) Spectroscopy, Kate Spalding, Franck Bonnier, Clément Bruno, Hélène Blasco, Ruth E. Board, Isabelle Benz-De-Bretagne, Hugh Byrne, Holly J. Butler, Igor Chourpa, Pretheepan Radhakrishnan, Matthew J. Baker

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Changes in protein concentrations within human blood are used as an indicator for nutritional state, hydration and underlying illnesses. They are often measured at regular clinical appointments and the current analytical process can result in long waiting times for results and the need for return patient visits. Attenuated total reflectance – Fourier transform infrared (ATR-FTIR) spectroscopy has the ability to detect minor molecular differences, qualitatively and quantitatively, in biofluid samples, without extensive sample preparation. ATR-FTIR can return an analytical measurement almost instantaneously and therefore could be deemed as an ideal technique for monitoring molecular alterations in blood within the clinic. …

Raman Spectroscopy Detects Biochemical Changes Due To Different Cell Culture Environments In Live Cells In Vitro, Mahmoud Gargotti, Esen Efeoglu, Hugh Byrne, Alan Casey

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The in vitro cell culture environment can impact on cell biochemistry and cell cycle. The manifestation of such substrate-induced changes in cell cycle in the Raman microspectroscopic profiles of cell cultures is investigated at the level of nucleolus, nucleus and cytoplasm. HeLa immortalised human cervical cells and HaCaT dermal cells were cultured on three different substrates, conventional polystyrene cell culture dishes, CaF2 slides as a commonly used Raman substrate, and glass slides coated with collagen rat tail, as a mimic of the extra-cellular matrix (ECM) environment. A cell cycle study, based on percentage DNA content, as determined using propidium iodide …

Raman Spectroscopic Analysis Of High Molecular Weight Proteins In Solution: Considerations For Sample Analysis And Data Pre-Processing, Drishya Parachalil, Brenda B. Brankin, Jennifer Mcintyre, Hugh Byrne

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This study explores the potential of Raman spectroscopy, coupled with multivariate regression techniques and a protein separation technique (ion exchange chromatography), to quantitatively monitor diagnostically relevant changes in high molecular weight proteins in liquid plasma. Measurement protocols to detect the imbalances in plasma proteins as an indicator of various diseases using Raman spectroscopy are optimised, such that strategic clinical applications for early stage disease diagnostics can be evaluated. In a simulated plasma protein mixture, concentrations of two proteins of identified diagnostic potential (albumin and fibrinogen) were systematically varied within physiologically relevant ranges. Scattering from the poorly soluble fibrinogen fraction is …

Nanostructured Apatite-Mullite Glass-Ceramics For Enhanced Primary Human Osteoblast Cell Response, Gordon Cooke, Conor Dunne, Sarah Keane, Daithi De Faoite, Seamas Donnelly, Kenneth Stanton

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This work investigates the difference in viability of primary human foetal osteoblast cells on a glass-ceramic surface with nanoscale topography relative to viability on a smooth glass-ceramic surface containing a bioactive phase. Apatite-mullite glass-ceramics containing bioactive fluorapatite (Ca₁₀(PO₄)₆F₂) and bioinert mullite (Si₂Al₆O₁₃) were synthesised and subsequent heat-treatment was optimised to form nano-sized fluorapatite crystals. Etching was used to selectively remove the bioactive phase, producing a surface with disordered nanoscale topography. Cells were seeded onto a smooth polished glass-ceramic substrate with the bioactive phase intact, an etched …

Moral Commitments In Cost-Benefit Analysis, Eric A. Posner, Cass R. Sunstein

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No abstract provided.

Probability Models And Compounding, David L. Farnsworth, James E. Marengo

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We present the case that the ideas contained in a particular sequence of formulas are important in probability and statistics. The synthesis offered by the concepts in the sequence can be very valuable. Facility with this sequence and its underpinnings should be in the skill set of anyone who uses or studies probability or statistics. For illustrative purposes, we give applications to mixture distributions and Bayesian analyses.

Risk And Resilience In Health Data Infrastructure, W. Nicholson Price Ii

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Today’s health system runs on data. However, for a system that generates and requires so much data, the health care system is surprisingly bad at maintaining, connecting, and using those data. In the easy cases of coordinated care and stationary patients, the system works—sometimes. But when care is fragmented, fragmented data often result. Fragmented data create risks both to individual patients and to the system. For patients, fragmentation creates risks in care based on incomplete or incorrect information, and may also lead to privacy risks from a patched together system. For the system, data fragmentation hinders efforts to improve efficiency …

Off-Target Effects Of Drugs That Disrupt Human Mitochondrial Dna Maintenance., Matthew J Young

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Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency syndrome. Development of severe mitochondrial toxicity has been well documented in patients infected with HIV and administered NRTIs. In vitro biochemical experiments have demonstrated that the replicative mitochondrial DNA (mtDNA) polymerase gamma, Polg, is a sensitive target for inhibition by metabolically active forms of NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs). Once incorporated into newly synthesized daughter strands NtRTIs block further DNA polymerization reactions. Human cell culture and animal studies have demonstrated that cell lines and mice exposed to NRTIs …

Artificial Intelligence In Health Care: Applications And Legal Implications, W. Nicholson Price Ii

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Artificial intelligence (AI) is rapidly moving to change the healthcare system. Driven by the juxtaposition of big data and powerful machine learning techniques—terms I will explain momentarily—innovators have begun to develop tools to improve the process of clinical care, to advance medical research, and to improve efficiency. These tools rely on algorithms, programs created from healthcare data that can make predictions or recommendations. However, the algorithms themselves are often too complex for their reasoning to be understood or even stated explicitly. Such algorithms may be best described as “black-box.” This article briefly describes the concept of AI in medicine, including …

Annotation Of Cultivar Variations At The Multigeneic Rhg1/Rfs2 Locus: Polymorphisms Underling Alteraannotation Of Cultivar Variations At The Multigeneic Rhg1/Rfs2 Locus: Polymorphisms Underling Alterations Of Root Development And Pest Resistancetions Of Root Development And Pest Resistance, Naghmeh Hemmati, Matt Geisler, Naresh Pola, Khalid Meksem, David A. Lightfoot

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Soybean (Glycine max (L.) Merr.) suffers yield loss due to root infection from soil infestation by Heterodera glycine I. (soybean cyst nematode SCN) and Fusarium virguliforme (Aoki; sudden death syndrome (SDS)). The major locus for SCN and SDS resistance has previously been identified as Rhg1/Rfs2 (chr18; LG G) (site reference). The objective of this experiment was to compare the Sanger DNA sequence of a resistant cultivar (‘Forrest’) and two susceptible cultivars (‘Williams 82’ and ‘Asgrow A3244’). Sequences were downloaded from GenBank for Williams 82, Phytzome for A3244 and a newly sequenced BAC-B73P06 (82,157 bp) encompassing the Rfs2/Rhg1 locus. Using the …

Additional Polymorphisms Linked To Soybean Cyst Nematode Resistance At The Rhg4 Locus, Oleksandra Zatserklyana, Khalid Meksem, David A. Lightfoot

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Glycine max L. Merr., (soybean) is one of the major crops in the United States, south America and Asia. Yet, the seed yield of soybean is significantly reduced due to Heterodera glycines (Ichinohe), the soybean cyst nematode (SCN). SCN is one of the most destructive pests and pathogens of soybean because the main methods for control have proven difficult. Lineages of soybean that are resistant to SCN have been developed but it is yet unknown what all the molecular causes of this resistance are. Rhg1 and Rhg4 loci are two of about 10 loci that underlie resistance. The Rhg4 locus, …

Characterisation Of Cold Plasma Treated Beef And Dairy Lipids Using Spectroscopic And Chromatographic Methods, Chaitanya Sarangapani, David Dorran, Julie Dunne, Patrick J. Cullen, Paula Bourke

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The efficacy of cold plasma for inactivation of food-borne pathogens in foods is established. However, insights on cold plasma-food interactions in terms of quality effects, particularly for oils and fats, are sparse. This study evaluated plasma-induced lipid oxidation of model matrices, namely dairy and meat fats. Product characterisation was performed using FTIR, ¹H NMR and chromatographic techniques. The oxidation of lipids by cold plasma followed the Criegee mechanism and typical oxidation products identified included ozonides, aldehydes (hexanal, pentenal, nonanal and nonenal) and carboxylic acids (9-oxononanoic acid, octanoic acid, nonanoic acid), along with hydroperoxides (9- and 13-hydroperoxy-octadecadienoylglycerol species). However, these …

Whole Genome Sequencing Of Rhodotorula Mucilaginosa Isolated From The Chewing Stick (Distemonanthus Benthamianus): Insights Into Rhodotorula Phylogeny, Mitogenome Dynamics And Carotenoid Biosynthesis, Han Ming Gan, Bolaji N. Thomas, Nicole T. Cavanaugh, Grace H. Morales, Ashley N. Mayers, Michael A. Savka, Andre O. Hudson

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In industry, the yeast Rhodotorula mucilaginosa is commonly used for the production of carotenoids. The production of carotenoids is important because they are used as natural colorants in food and some carotenoids are precursors of retinol (vitamin A). However, the identification and molecular characterization of the carotenoid pathway/s in species belonging to the genus Rhodotorula is scarce due to the lack of genomic information thus potentially impeding effective metabolic engineering of these yeast strains for improved carotenoid production. In this study, we report the isolation, identification, characterization and the whole nuclear genome and mitogenome sequence of the endophyte R. mucilaginosa …

Efficacy And Mechanistic Insigh Endocrine Disruptor Degradation Using Atmospheric Air Plasma, Chaitanya Sarangapani, Martin Danaher, Brijesh Tiwari, Peng Lu, Paula Bourke, Patrick J. Cullen

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Endocrine disruptors are a class of contaminants found in water and process effluents at low concentrations. They are of concern due to their high estrogenic potency. Their presence in the environment has led to the search for effective techniques for their removal in wastewater. For this purpose, an atmospheric air plasma reactor was employed for the study of the degradation of three endocrine disruptor chemicals (EDC) namely; bisphenol A (BPA), estrone (E1) and 17β- 27 estradiol (E2) within a model dairy effluent. Identification of the plasma induced active species both in the gas and liquid phases were performed. Also studied …

Development Of The Central Dogma Concept Inventory (Cdci) Assessment Tool, Dina L. Newman, Christopher W. Snyder, J. Nick Fisk, Leslie Kate Wright

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Scientific teaching requires scientifically constructed, field-tested instruments to accurately evaluate student thinking and gauge teacher effectiveness. We have developed a 23-question, multiple select–format assessment of student understanding of the essential concepts of the central dogma of molecular biology that is appropriate for all levels of undergraduate biology. Questions for the Central Dogma Concept Inventory (CDCI) tool were developed and iteratively revised based on student language and review by experts. The ability of the CDCI to discriminate between levels of understanding of the central dogma is supported by field testing (N = 54), and large-scale beta testing (N = …

Evasion Of Host Innate Immunity By Emerging Viruses: Antagonizing Host Rig-I Pathways, Maureen Ferran, Gary Skuse

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Viruses confront a seemingly dichotomous relationship with their host cells. They must overcome host defenses in order to complete their infectious cycles and generate new viruses yet the host must remain healthy and hospitable for that to take place. Shortly after infection, the RIGI-like receptors (RLRs) within the cytoplasm of the infected cell recognize foreign motifs present in the pathogen. The host responds by activating a signaling pathway that leads to activation of cellular transcription factors, including the NF-κB and interferon regulatory factor 3 (IRF3), that are necessary for induction of the type 1 interferon genes. Many viruses subdue components …

Genome Of Wild Olive And The Evolution Of Oil Biosynthesis, Turgay Unver, Hassan Ghazal, Oussama Badad, Pavan Kasarla, Vincent Colantonio, David Lightfoot, Marc Van Montagu

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Here we present the genome sequence and annotation of the wild olive tree (Olea europaea var. sylvestris), called oleaster, which is considered an ancestor of cultivated olive trees. More than 50,000 protein-coding genes were predicted, a majority of which could be anchored to 23 pseudochromosomes obtained through a newly constructed genetic map. The oleaster genome contains signatures of two Oleaceae lineage-specific paleopolyploidy events, dated at ∼28 and ∼59 Mya. These events contributed to the expansion and neofunctionalization of genes and gene families that play important roles in oil biosynthesis. The functional divergence of oil biosynthesis pathway genes, such as FAD2, …

Reciprocal Amplification Of Caspase-3 Activity By Nuclear Export Of A Putative Human Rna-Modifying Protein, Pus10 During Trail-Induced Apoptosis., Sujata Jana, Andrew C Hsieh, Ramesh Gupta

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Pus10 is a pseudouridine synthase present in Archaea and Eukarya, but not in Bacteria and yeast. It has been suggested that the human PUS10 (DOBI) gene is needed during TRAIL-induced apoptosis. We analyzed the role of PUS10 in TRAIL-induced apoptosis by immunofluorescence, immunoblotting and several indicators of apoptosis. We examined several TRAIL-sensitive cell lines and we also examined some resistant cell lines after treatment with cycloheximide. PUS10 is mainly present in the nucleus. Early during apoptosis, PUS10 translocates to mitochondria via CRM1-mediated export with the concurrent release of cytochrome c and SMAC. Caspase-3 is required for PUS10 translocation, which reciprocally …

The Value Of Instability: An Investigation Of Intra-Subject Variability In Brain Activity Among Obese Adolescent Girls, Lance O. Bauer, Rebecca J. Houston

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BACKGROUND: The present study investigated the value of intra-subject variability (ISV) as a metric for revealing differences in cognition and brain activation associated with an obese versus lean body mass.

METHODS: Ninety-six adolescents with a lean body mass (BMI %-ile = 5-85), and 92 adolescents with an obese body mass (BMI %-ile >=95), performed two tasks (Stroop and Go/NoGo) challenging response inhibition skills. The standard deviations and averages of their reaction time and P300 electroencephalographic responses to task stimuli were computed across trials.

RESULTS: During the Go/NoGo task, the reaction times of subjects with an obese body mass were more …

K-Bit-Swap: A New Operator For Real-Coded Evolutionary Algorithms, Aram Ter-Sarkisov, Stephen Marsland

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There has been a variety of crossover operators proposed for Real-Coded Genetic Algorithms (RCGAs), which recombine values from the same location in pairs of strings. In this article we present a recombination operator for RC- GAs that selects the locations randomly in both parents, and compare it to mainstream crossover operators in a set of experiments on a range of standard multidimensional optimization problems and a clustering problem. We present two variants of the operator, either selecting both bits uniformly at random in the strings, or sampling the second bit from a normal distribution centered at the selected location in …

Phytochemicals: Extraction, Isolation, And Identification Of Bioactive Compounds From Plant Extracts, Ammar Altemimi, Naoufal Lakhssassi, Azam Baharlouei, Dennis G. Watson, David A. Lightfoot

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There are concerns about using synthetic phenolic antioxidants such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) as food additives because of the reported negative effects on human health. Thus, a replacement of these synthetics by antioxidant extractions from various foods has been proposed. More than 8000 different phenolic compounds have been characterized; fruits and vegetables are the prime sources of natural antioxidants. In order to extract, measure, and identify bioactive compounds from a wide variety of fruits and vegetables, researchers use multiple techniques and methods. This review includes a brief description of a wide range of different assays. The …

Comparative Studies Of Cellular Viability Levels On 2d And 3d In Vitro Culture Matrices, Alan Casey, Hugh Byrne, Mahmoud Gargotti, Ulises Lopez Gonzalez

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In this study, the cellular viability and function of immortalized human cervical and dermal cells are monitored and compared in conventional 2D and two commercial 3D membranes, Collagen and Geltrex, of varying working concentration and volume. Viability was monitored with the aid of the Alamar Blue assay, cellular morphology was monitored with confocal microscopy, and cell cycle studies and cell death mechanism studies were performed with flow cytometry. The viability studies showed apparent differences between the 2D and 3D culture systems, the differences attributed in part to the physical transition from 2D to 3D environment causing alterations to effective resazurin …

Application Of Variational Principle To Form Reduced Fluid-Structure Interaction Models In Bifurcated Networks, Alexander S. Liberson, Yashar Seyed Vahedein, David A. Borkholder

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Reduced fluid-structure interaction models have received a considerable attention in recent years being the key component of hemodynamic modeling. A variety of models applying to specific physiological components such as arterial, venous and cerebrospinal fluid (CSF) circulatory systems have been developed based on different approaches. The purpose of this paper is to apply the general approach based on Hamilton’s variational principle to create a model for a viscous Newtonian Fluid - Structure Interaction (FSI) in a compliant bifurcated network. This approach provides the background for a correct formulation of reduced FSI models with an account for arbitrary nonlinear visco-elastic properties …

Dietary Phytochemicals As Inhibitors Of Primary Amine Oxidase, Padraig Shanahan, Jeffrey O'Sullivan, Keith F. Tipton, Gemma Kinsella, Barry J. Ryan, Gary T. Henehan

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Phytochemicals such as methylxanthines, catechins and polyphenols show health benefits in a range of diseases although their mechanism of action is not fully understood. Primary Amine Oxidase (PrAO) is widely recognised as a therapeutic drug target for the treatment of inflammatory, vascular and neurodegenerative diseases. Previous work in our laboratories showed that caffeine inhibited bovine PrAO activity with a Ki of 1.0mM. In the present study we examined a range of methylxanthines and catechins as inhibitors of bovine PrAO. The methylxanthines tested were caffeine, paraxanthine, theophylline, theobromine and 7-methylxanthine. Of these, only theobromine was an inhibitor with an IC50 of …

Evaluation Of The Antimicrobial Activities Of Ultrasonicated Spinach Leaf Extracts Using Rapd Markers And Electron Microscopy, Ammar Badran Altemimi, Naoufal Lakhssassi, Amer Abughazaleh, David Lightfoot

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Spinach (Spinacia oleracea L.) leaves represent an important dietary source of nutrients, antioxidants, and antimicrobials. As such, spinach leaves play an important role in health and have been used in the treatment of human diseases since ancient times. Here the aims were to optimize the extraction methods for recovering antimicrobial substances of spinach leaves, determine the minimum inhibitory concentrations (MICs) of the antimicrobial substances against Escherichia coli and Staphylococcus aureus and finally, evaluate the effects of spinach leaves’ antimicrobials on bacterial DNA using central composite face centered methods (CCFC). The effect of the extracts on both Gram positive and …

An Evaluation Of The Efficiency Of Compartmented Alginate Fibres Encapsulating Rejuvenator As Asphalt Pavement Healing System, Amir Tabakovic, Luke Schuyffel, Aleksandar Karac, Erik Schlangen

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This paper explores the potential methods for evaluating a healing system for asphalt pavements. The healing system under investigation involves compartmented calcium-alginate fibres encapsulating an asphalt binder healing agent (rejuvenator). This system presents a novel method of incorporating rejuvenators into asphalt pavement mixtures. The compartmented fibres are used to distribute the rejuvenator throughout the pavement mixture, thereby overcoming some of the problems associated with alternate asphalt pavement healing methods, i.e., spherical capsules and hollow fibres. The asphalt healing efficiency methods to be evaluated in this paper include: (i) standard test methods for asphalt pavements, such as the Indirect Tensile Strength …

Antifungal Potential Of Copper(Ii), Manganese(Ii) And Silver(I) 1,10-Phenanthroline Chelates Against Multidrug-Resistant Fungal Species Forming The Candida Haemulonii Complex: Impact On The Planktonic And Biofilm Lifestyles, Rafael M. Gandra, Pauraic Mc Carron, Mariana F. Fernandes, Lívia S. Ramos, Thaís P. Mello, Ana Carolina Aor, Marta H. Branquinha, Malachy Mccann, Michael Devereux, André L. S. Santos

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Candida haemulonii, Candida haemulonii var. vulnera and Candida duobushaemulonii, which form the C. haemulonii complex, are emerging etiologic agents of fungal infections known to be resistant to the most commonly used antifungals. The well-established anti-Candida potential ofmetal complexes containing 1,10-phenanthroline (phen) ligands encouraged us to evaluate different copper(II), manganese(II), and silver(I) phen chelates for their ability to inhibit planktonic growth and biofilm of C. haemulonii species complex. Two novel coordination complexes, {[Cu(3,6,9-tdda)(phen)2].3H2O.EtOH}n and [Ag2(3,6,9-tdda)(phen)4].EtOH (3,6,9-tddaH2 = 3,6,9-trioxaundecanedioic acid), were synthesized in a similar fashion to the other, previously documented, sixteen copper(II), manganese(II), and silver(I) chelates employed herein. Three isolates of …