Search results for: Orla Coleman

Authors: Kevin Kellner, Nga Lao, Orla Coleman, Paula Meleady, Niall Barron

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Chinese Hamster Ovary (CHO) cells are the prominent cell line used in biopharmaceutical production. To improve yields and find beneficial bioprocess phenotypes genetic engineering plays an essential role in recent research. The miR-23 cluster, specifically miR-24 and miR-27, was first identified as differentially expressed during hypothermic conditions suggesting a role in proliferation and productivity in CHO cells. In this study, we used sponge decoy technology to stably deplete the miRNA expression of the cluster. Furthermore, we implemented the CRISPR/Cas9 system to knockdown miRNA expression. Sponge constructs were designed for an imperfect binding of the miRNA target, protecting from RISC mediated cleavage. GuideRNAs for the CRISPR/Cas9 system were designed to target the seed region of the miRNA. The expression of mature miRNA and precursor were confirmed using RT-qPCR. For both approaches stable expressing mixed populations were generated and characterised in batch cultures. It was shown, that CRISPR/Cas9 can be implemented in CHO cells with achieving high knockdown efficacy of every single member of the cluster. Targeting of one miRNA member showed that its genomic paralog is successfully targeted as well. The stable depletion of miR-24 using CRISPR/Cas9 showed increased growth and specific productivity in a CHO-K1 mAb expressing cell line. This phenotype was further characterized using quantitative label-free LC-MS/MS showing 186 proteins differently expressed with 19 involved in proliferation and 26 involved in protein folding/translation. Targeting miR-27 in the same cell line showed increased viability in late stages of the culture compared to the control. To evaluate the phenotype in an industry relevant cell line; the miR-23 cluster, miR-24 and miR-27 were stably depleted in a Fc fusion CHO-S cell line which showed increased batch titers up to 1.5-fold. In this work, we highlighted that the stable depletion of the miR-23 cluster and its members can improve the bioprocess phenotype concerning growth and productivity in two different cell lines. Furthermore, we showed that using CRISPR/Cas9 is comparable to the traditional sponge decoy technology.

Keywords: Chinese Hamster ovary cells, CRISPR/Cas9, microRNAs, sponge decoy technology

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Authors: Orla Muldoon, Tamaryn Nicolson, Mike Quayle, Aisling O'Donnell

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Psychology most often considers the role of experience and behaviour in shaping health at the individual level. On the other hand epidemiology has long considered risk at the wider group or structural level. Here we use the social identity approach to integrate group-level risk with individual level behaviour. Using a social identity approach we demonstrate that group or macro-level factors impact implicitly and profoundly in everyday ways at the level of individuals, via social identities. We illustrate how identities related to race, gender and inequality intersect to affect HIV/AIDS risk and AIDS treatment behaviours; how social identity processes drive stigmatising consequences of HIV and AIDS, and promote positive and effective interventions. We conclude by arguing that the social identity approach offers the field an explanatory framework that conceptualizes how social and political forces intersect with individual identity and agency to affect human health.

Keywords: social identity approach, HIV/AIDS, Africa, HIV risk, race, gender

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Authors: Amanda Coleman, Estefanía Gonzalez

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Empathy is considered an essential skill for engaging with social work clients. Drawing from developments in medical education, researchers will conduct and evaluate a three-part pilot theatre workshop with master level social work students (n ≈ 30) to evaluate the workshop's ability to enhance empathy among participants. Outcomes will be measured using semi-structured post-intervention interviews with a subset of participants (n ≈ 10) as well post-intervention written reflections and pre-and-post intervention quantitative evaluation of empathy using King and Holosko’s 2011 Empathy Scale for Social Workers. The content of the workshop will differ from traditional role plays, which are common in social work education, in that it will draw from role theory and research on creative empathy to emphasize role reversal with clients. Workshops will be held February and March of 2017 with preliminary findings available by April.

Keywords: education, empathy, social work, theatre

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Authors: Eric Huang, Coleman DeLude, Justin Romberg, Saibal Mukhopadhyay, Madhavan Swaminathan

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High performance computing (HPC) based emulators can be used to model the scattering from multiple stationary and moving targets for RADAR applications. These emulators rely on the RADAR Cross Section (RCS) of the targets being available in complex scenarios. Representing the RCS using tables generated from electromagnetic (EM) simulations is often times cumbersome leading to large storage requirement. This paper proposed a spherical harmonic based anisotropic scatterer model to represent the RCS of complex targets. The problem of finding the locations and reflection profiles of all scatterers can be formulated as a linear least square problem with a special sparsity constraint. This paper solves this problem using a modified Orthogonal Matching Pursuit algorithm. The results show that the spherical harmonic based scatterer model can effectively represent the RCS data of complex targets.

Keywords: RADAR, RCS, high performance computing, point scatterer model

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Authors: F. Rahimi Dehgolan, S. E. Khadem, S. Bab, M. Najafee

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Nowadays, using rotating systems like shafts and disks in industrial machines have been increased constantly. Dynamic stability is one of the most important factors in designing rotating systems. In this study, linear frequencies and stability of a coupled continuous flexible rotor-disk-blades system are studied. The Euler-Bernoulli beam theory is utilized to model the blade and shaft. The equations of motion are extracted using the extended Hamilton principle. The equations of motion have been simplified using the Coleman and complex transformations method. The natural frequencies of the linear part of the system are extracted, and the effects of various system parameters on the natural frequencies and decay rates (stability condition) are clarified. It can be seen that the centrifugal stiffening effect applied to the blades is the most important parameter for stability of the considered rotating system. This result highlights the importance of considering this stiffing effect in blades equation.

Keywords: rotating shaft, flexible blades, centrifugal stiffness, stability

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Authors: L. Lindsay, S. A. Coleman, D. Kerr, B. J. Taylor, A. Moorhead

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Cognitive decline and frailty is apparent in older adults leading to an increased likelihood of the risk of falling. Currently health care professionals have to make professional decisions regarding such risks, and hence make difficult decisions regarding the future welfare of the ageing population. This study uses health data from The Irish Longitudinal Study on Ageing (TILDA), focusing on adults over the age of 50 years, in order to analyse health risk factors and predict the likelihood of falls. This prediction is based on the use of machine learning algorithms whereby health risk factors are used as inputs to predict the likelihood of falling. Initial results show that health risk factors such as long-term health issues contribute to the number of falls. The identification of such health risk factors has the potential to inform health and social care professionals, older people and their family members in order to mitigate daily living risks.

Keywords: classification, falls, health risk factors, machine learning, older adults

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Authors: Orla McConnell, Cormac MacMahon, Jen Harvey

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Ireland’s national professional development framework for those who teach in higher education, aims to provide guidance and leadership in the planning, developing and engaging in professional development practices. A series of pilot projects have been initiated to help explore the framework’s likely utility and acceptance by educators and their institutions. These projects require engagement with staff in the interpretation and adaption of the framework within their working contexts. The purpose of this paper is to outline the development of one such project with engineering educators at three Institutes of Technology seeking designation as a technological university. The initiative aims to gain traction in the acceptance of the framework with the engineering education community by linking core and discipline-specific teaching and learning competencies with professional development activities most valued by engineering educators. Informed by three strands of literature: professional development in higher education; engineering education; and teaching and learning training provisions, the project begins with a survey of all those involved in teaching and learning in engineering across the three institutes. Based on engagement with key stakeholders, subsequent qualitative research informs the contextualization of the national framework for discipline-specific and institutional piloting. The paper concludes by exploring engineering educator perceptions of the national framework’s utility based on their engagement with the pilot process. Feedback from the pilot indicates that there is a significant gap between the professional development needs of engineering educators and the current professional development provision in teaching and learning.

Keywords: engineering education, pilot, professional development, teaching and learning

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Authors: M. C. Steyn

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Violence and entertainment are not mutually exclusive subjects in the Ancient Roman world, in reality they are closely knit together. Their world is permeated by repeated and continuous episodes of violence in its many manifestations, both sanctioned and spontaneous, most of which is considered as some form of entertainment, from plays and writings through the spectrum to the gladiatorial arena. In the 21st century this socio-psychological dynamic is manifested through the stage provided by the screen and what we watch in terms of TV, movies and games. This glorification of violence in a modern world is not out of place as seen in contemporary post apocalyptical/ dystopian literature, film and computer games where the act of violence, frowned upon by social norms and values, becomes sanctioned by the (un)real nature of the game: ‘I am not a violent person, violence is bad, this is just a game’. This paper will examine how violence is framed in the Ancient World and subsequently how it is received by popular culture to represent a world in which the maintenance of stability can only be achieved through officially sanctioned violence, whether sanctioned by the State or the gaming community. This argument will examine both ancient and modern critics of violence such as Senecca, Coleman and Foucault and framed by Baudrillard’s commentary on the post-modern conceptualization of reality.

Keywords: entertainment, violence, gladiatorial games, gaming

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Authors: Sinead Impey, Damon Berry, Selma Furtado, Miriam Galvin, Loretto Grogan, Orla Hardiman, Lucy Hederman, Mark Heverin, Vincent Wade, Linda Douris, Declan O'Sullivan, Gaye Stephens

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Healthcare is a knowledge-rich environment. This knowledge, while valuable, is not always accessible outside the borders of individual clinics. This research aims to address part of this problem (at a study site) by constructing a maximal data set (knowledge artefact) for motor neurone disease (MND). This data set is proposed as an initial knowledge base for a concurrent project to develop an MND patient data platform. It represents the domain knowledge at the study site for the duration of the research (12 months). A knowledge elicitation method was also developed from the lessons learned during this process - the WICKED method. WICKED is an anagram of the words: eliciting and confirming data, information, knowledge, wisdom. But it is also a reference to the concept of wicked problems, which are complex and challenging, as is eliciting expert knowledge. The method was evaluated at a second site, and benefits and limitations were noted. Benefits include that the method provided a systematic way to manage data, information, knowledge and wisdom (DIKW) from various sources, including healthcare specialists and existing data sets. Limitations surrounded the time required and how the data set produced only represents DIKW known during the research period. Future work is underway to address these limitations.

Keywords: healthcare, knowledge acquisition, maximal data sets, action design science

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Authors: S. De Curtis, L. Delle Rose, S. Moretti, K. Yagyu

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Supersymmetry and compositeness are the two prevalent paradigms providing both a solution to the hierarchy problem and motivation for a light Higgs boson state. An open door towards the solution is found in the context of 2-Higgs Doublet Models (2HDMs), which are necessary to supersymmetry and natural within compositeness in order to enable Electro-Weak Symmetry Breaking. In scenarios of compositeness, the two isospin doublets arise as pseudo Nambu-Goldstone bosons from the breaking of SO(6). By calculating the Higgs potential at one-loop level through the Coleman-Weinberg mechanism from the explicit breaking of the global symmetry induced by the partial compositeness of fermions and gauge bosons, we derive the phenomenological properties of the Higgs states and highlight the main signatures of this Composite 2-Higgs Doublet Model at the Large Hadron Collider. These include modifications to the SM-like Higgs couplings as well as production and decay channels of heavier Higgs bosons. We contrast the properties of this composite scenario to the well-known ones established in supersymmetry, with the MSSM being the most notorious example. We show how 2HDM spectra of masses and couplings accessible at the Large Hadron Collider may allow one to distinguish between the two paradigms.

Keywords: beyond the standard model, composite Higgs, supersymmetry, Two-Higgs Doublet Model

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Authors: Trevor Kroeger, Hayden Williams, Edward Holzinger, David Coleman, Brian Haberman

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The network connectivity of medical devices is increasing at a rapid rate. Many medical devices, such as vital sign monitors, share information via wireless or wired connections. However, these connectivity options suffer from a variety of well-known limitations. Wireless connectivity, especially in the unlicensed radio frequency bands, can be disrupted. Such disruption could be due to benign reasons, such as a crowded spectrum, or to malicious intent. While wired connections are less susceptible to interference, they inhibit the mobility of the medical devices, which could be critical in a variety of scenarios. This work explores the application of Light Fidelity (Li-Fi) communication to enhance the security, performance, and mobility of medical devices in connected healthcare scenarios. A simple bridge for connected devices serves as an avenue to connect traditional medical devices to the Li-Fi network. This bridge was utilized to conduct bandwidth tests on a small Li-Fi network installed into a Mock-ICU setting with a backend enterprise network similar to that of a hospital. Mobile and stationary tests were conducted to replicate various different situations that might occur within a hospital setting. Results show that in room Li-Fi connectivity provides reasonable bandwidth and latency within a hospital like setting.

Keywords: hospital, light fidelity, Li-Fi, medical devices, security

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Authors: M. A. Alqahtani, D. P. Coleman, N. D. Pugh, L. D. M. Nokes

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In diagnostic ultrasound, the echo graphic B-scan texture is an important area of investigation since it can be analyzed to characterize the histological state of internal tissues. An important factor requiring consideration when evaluating ultrasonic tissue texture is the depth. The effect of attenuation with depth of ultrasound, the size of the region of interest, gain, and dynamic range are important variables to consider as they can influence the analysis of texture features. These sources of variability have to be considered carefully when evaluating image texture as different settings might influence the resultant image. The aim of this study is to investigate the effect of depth on the texture features in-vivo using a 3D ultrasound probe. The left leg medial head of the gastrocnemius muscle of 10 healthy subjects were scanned. Two regions A and B were defined at different depth within the gastrocnemius muscle boundary. The size of both ROI’s was 280*20 pixels and the distance between region A and B was kept constant at 5 mm. Texture parameters include gray level, variance, skewness, kurtosis, co-occurrence matrix; run length matrix, gradient, autoregressive (AR) model and wavelet transform were extracted from the images. The paired t –test was used to test the depth effect for the normally distributed data and the Wilcoxon–Mann-Whitney test was used for the non-normally distributed data. The gray level, variance, and run length matrix were significantly lowered when the depth increased. The other texture parameters showed similar values at different depth. All the texture parameters showed no significant difference between depths A and B (p > 0.05) except for gray level, variance and run length matrix (p < 0.05). This indicates that gray level, variance, and run length matrix are depth dependent.

Keywords: ultrasound image, texture parameters, computational biology, biomedical engineering

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Authors: Vilar, Katila

Abstract:

Rapid urbanization have made of spontaneous settlements one of the dominant´s social subjects of the XXIst century. Currently, it´s recognized that these territories cannot easily be eradicated and are a way of life to many populations of emergent countries. Since late 90s, there is an urgent concern in finding planning and efficient urban design strategies to poverty reduction, spatial integration and social inclusion of low-income communities. The article aims to identify, understand and evaluate the social inclusion´s processes through the urban transformation that has been undertaken in Moravia and how they affected the community´s social capital. To achieve this objective, we start to analyse the PPMIM´s planning discourse in which prevails the sustainability´s concept, to further identify, through the analysis of the project carried out, the urban design strategies implemented and their impact on the perception and on the community´s experience, and, finally, how these focused on the social capital. It relies on concepts such as urban design, social capital, local development and sustainability. At the urban design level it starts on the current principles of “making places”, on the new urbanism concepts and on the practices on the ground carried out by a new generation of architects/planners whose have the main ethical approach in order to create more opportunities and greater social impact to these territories. At the social capital´s level and on the development´s theory, relies on authors such as Coleman, Putman Kliksberg and Amartya Sen. Finally, it aims to address a general discussion about the positive and negative implications of slum upgrading programmes and some necessary recommendations for urban design and social capital can really be translated into real resources for the self sustainable development of low-income communities and their future generations.

Keywords: local and sustainable development, social capital, spontaneous settlements, urban design

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Authors: Ronald Collins, Jonathon Coleman, Joel Dasari, George Holt, Carl Metelko, Matthew Murdoch, Alexander Morgan, Yan-Jie Schnellbach, Robert Mills, Gareth Edwards, Alexander Roberts

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At the Wylfa Magnox Power Plant between 2014–2016, the VIDARR prototype anti-neutrino detector was deployed. It is comprised of extruded plastic scintillating bars measuring 4 cm × 1 cm × 152 cm and utilised wavelength shifting fibres (WLS) and multi-pixel photon counters (MPPCs) to detect and quantify radiation. During deployment, it took cosmic muon data in accidental coincidence with the anti-neutrino measurements with the power plant site buildings obscuring the muon sky. Cosmic muons have a significantly higher probability of being attenuated and/or absorbed by denser objects, and so one-sided cosmic muon tomography was utilised to image the reactor site buildings. In order to achieve clear building outlines, a control data set was taken at the University of Liverpool from 2016 – 2018, which had minimal occlusion of the cosmic muon flux by dense objects. By taking the ratio of these two data sets and using GEANT4 simulations, it is possible to perform a one-sided cosmic muon tomography analysis. This analysis can be used to discern specific buildings, building heights, and features at the Wylfa reactor site, including the reactor core/reactor core shielding using ∼ 3 hours worth of cosmic-ray detector live time. This result demonstrates the feasibility of using cosmic muon analysis to determine a segmented detector’s location with respect to surrounding buildings, assisted by aerial photography or satellite imagery.

Keywords: anti-neutrino, GEANT4, muon, tomography, occlusion

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Authors: Debit Datta, Jeffrey J. Coleman, Scott A. Enebak, Lori G. Eckhardt

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Loblolly pine (Pinus taeda) is a leading productive timber species in the southeastern USA. Over the past three years, an emerging threat is expressed by successive needle defoliation followed by stunted growth and tree mortality in loblolly pine plantations. Considering economic significance, it has now become a rising concern among landowners, forest managers, and forest health state cooperators. However, the symptoms of the disease were perplexed somewhat with root disease(s) and recurrently attributed to invasive Phytophthora species due to the similarity of disease nature and devastation. Therefore, the study investigated the potential causal agent of this disease and characterized the fungi associated with loblolly pine needle defoliation in the southeastern USA. Besides, 70 trees were selected at seven long-term monitoring plots at Chatom, Alabama, to monitor and record the annual disease incidence and severity. Based on colony morphology and ITS-rDNA sequence data, a total of 28 species of fungi representing 17 families have been recovered from diseased loblolly pine needles. The native brown-spot pathogen, Lecanosticta acicola, was the species most frequently recovered from unhealthy loblolly pine needles in combination with some other common needle cast and rust pathogen(s). Identification was confirmed using morphological similarity and amplification of translation elongation factor 1-alpha gene region of interest. Tagged trees were consistently found chlorotic and defoliated from 2019 to 2020. The current emergence of the brown-spot pathogen causing loblolly pine mortality necessitates the investigation of the role of changing climatic conditions, which might be associated with increased pathogen pressure to loblolly pines in the southeastern USA.

Keywords: brown-spot needle blight, loblolly pine, needle defoliation, plantation forestry

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Authors: David C. Ni

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The current efforts for Grand Unification Theory (GUT) can be classified into General Relativity, Quantum Mechanics, String Theory and the related formalisms. In the geometric approaches for extending General Relativity, the efforts are establishing global and local invariance embedded into metric formalisms, thereby additional dimensions are constructed for unifying canonical formulations, such as Hamiltonian and Lagrangian formulations. The approaches of extending Quantum Mechanics adopt symmetry principle to formulate algebra-group theories, which evolved from Maxwell formulation to Yang-Mills non-abelian gauge formulation, and thereafter manifested the Standard model. This thread of efforts has been constructing super-symmetry for mapping fermion and boson as well as gluon and graviton. The efforts of String theory currently have been evolving to so-called gauge/gravity correspondence, particularly the equivalence between type IIB string theory compactified on AdS5 × S5 and N = 4 supersymmetric Yang-Mills theory. Other efforts are also adopting cross-breeding approaches of above three formalisms as well as competing formalisms, nevertheless, the related symmetries, dualities, and correspondences are outlined as principles and techniques even these terminologies are defined diversely and often generally coined as duality. In this paper, we firstly classify these dualities from the perspective of physics. Then examine the hierarchical structure of classes from mathematical perspective referring to Coleman-Mandula theorem, Hidden Local Symmetry, Groupoid-Categorization and others. Based on Fundamental Theorems of Algebra, we argue that rather imposing effective constraints on different algebras and the related extensions, which are mainly constructed by self-breeding or self-mapping methodologies for sustaining invariance, we propose a new addition, momentum-angular momentum duality at the level of electromagnetic duality, for rationalizing the duality algebras, and then characterize this duality numerically with attempt for addressing some unsolved problems in physics and astrophysics.

Keywords: general relativity, quantum mechanics, string theory, duality, symmetry, correspondence, algebra, momentum-angular-momentum

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Authors: Lisa M. Coleman

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The focus on disability, LGBTQ+, and internationalization has certainly been the subject of much research and programmatic across higher education. Many universities have entered into global partnerships with varying success and challenges across the various areas, including laws and policies. Attentiveness to the specific nuances of global inclusion, diversity, equity, belonging, and access (GIDBEA) and the leadership to support these efforts is crucial to the development of longstanding success across the programs. There have been a number of shifts related to diversification across student and alumni bodies. These shifts include but are not limited to how people identify gender, race, and sexuality (and the intersections across such identities), as well as trends across emerging and diverse disability communities. NYU is the most international campus in the United States, with the most campuses and sites outside of its county of origin and the most international students and exchange programs than any other university. As a result, the ongoing work related to GIDEBA is at the center of much of the leadership, administrative, and research efforts. Climate assessment work across NYU’s diverse global campus landscape will serve as the foundation to exemplify best practices related to data collection and dissemination, community and stakeholder engagement, and effective implementation of innovative strategies to close gap areas as identified. The data (quantitative and qualitative) and related research findings represent data collected from close to 22,000 stakeholders across the NYU campuses. The case study centers on specific methodological considerations, data integrity, stakeholder engagement from across student-faculty, staff, and alumni constituencies, and tactics to advance specific GIDBEA initiatives related to navigating shifting landscapes. Design thinking, incubation, and co-creation strategies have been employed to expand, leverage, actualize, and implement GIDBEA strategies that are – concrete, measurable, differentiated, and specific to global sites and regions and emerging trends.

Keywords: disability, LGBTQ+, DEI, research, case studies

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Olusola Omolola Olafuyi, Michael Coleman, Raj Kumar Singh Badhan

Abstract:

Introduction: Malaria in pregnancy has morbidity and mortality implication on both mother and unborn child. Piperaquine (PQ) based antimalarial treatment is emerging as a choice antimalarial for pregnant women in the face of resistance to current antimalarial treatment recommendation in pregnancy. Physiological and biochemical changes in pregnant women may affect the pharmacokinetics of the antimalarial drug in these. In malaria endemic regions other infectious diseases like HIV/AIDs are prevalent. Pregnant women who are co-infected with malaria and HIV/AID are at even more greater risk of death not only due to complications of the diseases but also due to drug-drug interactions (DDIs) between antimalarials (AMT) and antiretroviral (ARVs). In this study, physiologically based pharmacokinetic (PBPK) modelling was used to investigate the effect of physiological and biochemical changes on the impact of ARV mediated DDIs in pregnant women in three countries. Method: A PBPK model for PQ was developed on SimCYP® using published physicochemical and pharmacokinetic data of PQ from literature, this was validated in three customized population groups from Thailand, Sudan and Papua New Guinea with clinical data. Validation of PQ model was also done in presence of interaction with efavirenz (pre-validated on SimCYP®). Different albumin levels and pregnancy stages was simulated in the presence of interaction with standard doses of efavirenz and ritonavir. PQ day 7 concentration of 30ng/ml was used as the efficacy endpoint for PQ treatment.. Results: The median day 7 concentration of PQ remained virtually consistent throughout pregnancy and were satisfactory across the three population groups ranging from 26-34.1ng/ml; this implied the efficacy of PQ throughout pregnancy. DDI interaction with ritonavir and efavirenz resulted in modest effect on the day 7 concentrations of PQ with AUCratio ranging from 0.56-0.8 and 1.64-1.79 for efavirenz and ritonavir respectively over 10-40 gestational weeks, however, a reduction in human serum albumin level reflective of severe malaria resulted in significantly reduced the number of subjects attaining the PQ day 7 concentration in the presence of both DDIs. The model demonstrated that the DDI between PQ and ARV in pregnant women with different malaria severities can alter the pharmacokinetic of PQ.

Keywords: antiretroviral, malaria, piperaquine, pregnancy, physiologically-based pharmacokinetics

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Authors: Debit Datta, Jeffrey J. Coleman, Scott A. Enebak, Lori G. Eckhardt

Abstract:

Pinus taeda, commonly known as loblolly pine, is a crucial timber species native to the southeastern USA. An emerging problem has been encountered for the past few years, which is better to be known as loblolly pine needle defoliation (LPND), which is threatening the ecological health of southeastern forests and economic vitality of the region’s timber industry. Currently, more than 1000 hectares of loblolly plantations in Alabama are affected with similar symptoms and have created concern among southeast landowners and forest managers. However, it is still uncertain whether LPND results from one or the combination of several fungal pathogens. Therefore, the objectives of the study were to identify and characterize the fungi associated with LPND in the southeastern USA and document the damage being done to loblolly pine as a result of repeated defoliation. Identification of fungi was confirmed using classical morphological methods (microscopic examination of the infected needles), conventional and species-specific priming (SSPP) PCR, and ITS sequencing. To date, 17 species of fungi, either cultured from pine needles or formed fruiting bodies on pine needles, were identified based on morphology and genetic sequence data. Among them, brown-spot pathogen Lecanostica acicola has been frequently recovered from pine needles in both spring and summer. Moreover, Ophistomatoid fungi such as Leptographium procerum, L. terebrantis are associated with pine decline have also been recovered from root samples of the infected stands. Trees have been increasingly and repeatedly chlorotic and defoliated from 2019 to 2020. Based on morphological observations and molecular data, emerging loblolly pine needle defoliation is due in larger part to the brown-spot pathogen L. acoicola followed by pine decline pathogens L. procerum and L. terebrantis. Root pathogens were suspected to emerge later, and their cumulative effects contribute to the widespread mortality of the trees. It is more likely that longer wet spring and warmer temperatures are favorable to disease development and may be important in the disease ecology of LPND. Therefore, the outbreak of the disease is assumed to be expanded over a large geographical area in a changing climatic condition.

Keywords: brown-spot fungi, emerging disease, defoliation, loblolly pine

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Authors: Morteza Esfandiari, Shabnam Jabari, Heather MacGrath, David Coleman

Abstract:

Flood is a severe issue in different places in the world as well as the city of Fredericton, New Brunswick, Canada. The downtown area of Fredericton is close to the Saint John River, which is susceptible to flood around May every year. Recently, the frequency of flooding seems to be increased, especially after the fact that the downtown area and surrounding urban/agricultural lands got flooded in two consecutive years in 2018 and 2019. In order to have an explicit vision of flood span and damage to affected areas, it is necessary to use either flood inundation modelling or satellite data. Due to contingent availability and weather dependency of optical satellites, and limited existing data for the high cost of hydrodynamic models, it is not always feasible to rely on these sources of data to generate quality flood maps after or during the catastrophe. Height Above the Nearest Drainage (HAND), a state-of-the-art topo-hydrological index, normalizes the height of a basin based on the relative elevation along with the stream network and specifies the gravitational or the relative drainage potential of an area. HAND is a relative height difference between the stream network and each cell on a Digital Terrain Model (DTM). The stream layer is provided through a multi-step, time-consuming process which does not always result in an optimal representation of the river centerline depending on the topographic complexity of that region. HAND is used in numerous case studies with quite acceptable and sometimes unexpected results because of natural and human-made features on the surface of the earth. Some of these features might cause a disturbance in the generated model, and consequently, the model might not be able to predict the flow simulation accurately. We propose to include a previously existing stream layer generated by the province of New Brunswick and benefit from culvert maps to improve the water flow simulation and accordingly the accuracy of HAND model. By considering these parameters in our processing, we were able to increase the accuracy of the model from nearly 74% to almost 92%. The improved model can be used for generating highly accurate flood maps, which is necessary for future urban planning and flood damage estimation without any need for satellite imagery or hydrodynamic computations.

Keywords: HAND, DTM, rapid floodplain, simplified conceptual models

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Authors: Lunthita M. Duthely, John T. Avella, John Ganapati Coleman

Abstract:

For as many as one in three adolescents living in the United States, the adolescent years is a period of low well-being and mental health challenges—from depressive symptoms to mild to moderate psychological diagnoses. Longitudinal population health studies demonstrated that these challenges persist in young adulthood, and beyond. The positive psychology (PS) approach is a more preventative approach to well-being, which contrasts the traditional, deficits approach to curing mental illness. The research among adult populations formed the basis for PS studies among adolescents. The empirical evidence for the effectiveness of PS interventions exists for both adult and youth populations. Positive Psychology interventions target individuals’ strengths, such as hope and optimism, and positive emotions, such as gratitude. Positive psychology interventions such as increasing gratitude, proved effective in many outcomes among youth, including psychological, social, and academically-related outcomes. Although gratitude-inducing studies have been conducted for the past decade in the United States, few studies have been conducted among samples of urban youth, particularly youth of diverse cultural backgrounds. For nearly two decades, the secular practice of meditation has been tested among adults and more recently among youth, focused mostly among clinical samples. The field of Contemplative Sciences explores practices such as Hatha Yoga, Tai Chi, and Meditation, as preventative practices among children and adolescents. A more recent initiative is to explore Contemplative Practices in the school environment. Contemplative Practices yield a variety of positive outcomes, including academic, social, psychological, physiological, and neurological changes among children and adolescents. Again, few studies were conducted among adolescents of diverse cultural backgrounds. The purpose of this doctoral dissertation research study was to test a gratitude-meditation intervention among middle school students attending a public charter school, located in an urban region of Metropolitan Miami. The objective of this presentation is to summarize the challenges and success of bringing a positive psychology and meditation intervention into an urban middle school. Also, the most recent findings on positive psychology and meditation interventions conducted in school environments will be presented as well.

Keywords: adolescents, contemplative intervention, gratitude, secular meditation, positive psychology, school engagement, Sri Chinmoy

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Authors: Dagmara A. Niedziela, Mark P. Murphy, Orla M. Keane, Finola C. Leonard

Abstract:

Staphylococcus aureus is the most frequent cause of clinical and subclinical bovine mastitis in Ireland. Mastitis caused by S. aureus is often chronic and tends to recur after antibiotic treatment. This may be due to several virulence factors, including attributes that enable the bacterium to internalize into bovine mammary epithelial cells, where it may evade antibiotic treatment, or evade the host immune response. Four bovine-adapted lineages (CC71, CC97, CC151 and ST136) were identified among a collection of Irish S. aureus mastitis isolates. Genotypic variation of mastitis-causing strains may contribute to different presentations of the disease, including differences in milk somatic cell count (SCC), the main method of mastitis detection. The objective of this study was to investigate the influence of bacterial strain and lineage on host immune response, by employing cell culture methods in vitro as well as an in vivo infection model. Twelve bovine adapted S. aureus strains were examined for internalization into bovine mammary epithelial cells (bMEC) and their ability to induce an immune response from bMEC (using qPCR and ELISA). In vitro studies found differences in a variety of virulence traits between the lineages. Strains from lineages CC97 and CC71 internalized more efficiently into bovine mammary epithelial cells (bMEC) than CC151 and ST136. CC97 strains also induced immune genes in bMEC more strongly than strains from the other 3 lineages. One strain each of CC151 and CC97 that differed in their ability to cause an immune response in bMEC were selected on the basis of the above in vitro experiments. Fourteen first-lactation Holstein-Friesian cows were purchased from 2 farms on the basis of low SCC (less than 50 000 cells/ml) and infection free status. Seven cows were infected with 1.73 x 102 c.f.u. of the CC97 strain (Group 1) and another seven with 5.83 x 102 c.f.u. of the CC151 strain (Group 2). The contralateral quarter of each cow was inoculated with PBS (vehicle). Clinical signs of infection (temperature, milk and udder appearance, milk yield) were monitored for 30 days. Blood and milk samples were taken to determine bacterial counts in milk, SCC, white blood cell populations and cytokines. Differences in disease presentation in vivo between groups were observed, with two animals from Group 2 developing clinical mastitis and requiring antibiotic treatment, while one animal from Group 1 did not develop an infection for the duration of the study. Fever (temperature > 39.5⁰C) was observed in 3 animals from Group 2 and in none from Group 1. Significant differences in SCC and bacterial load between groups were observed in the initial stages of infection (week 1). Data is also being collected on cytokines and chemokines secreted during the course of infection. The results of this study suggest that a strain from lineage CC151 may cause more severe clinical mastitis, while a strain from lineage CC97 may cause mild, subclinical mastitis. Diversity between strains of S. aureus may therefore influence the clinical presentation of mastitis, which in turn may influence disease detection and treatment needs.

Keywords: Bovine mastitis, host immune response, host-pathogen interactions, Staphylococcus aureus

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Authors: Rebecca Dewfall, Mark Coleman, Vladimir Basabe

Abstract:

Oxide scale growth is an inevitable byproduct of the high temperature processing of steel. Blister is a phenomenon that occurs due to oxide growth, where high temperatures result in the swelling of surface scale, producing a bubble-like feature. Blisters can subsequently become embedded in the steel substrate during hot rolling in the finishing mill. This rolled in scale defect causes havoc within industry, not only with wear on machinery but loss of customer satisfaction, poor surface finish, loss of material, and profit. Even though blister is a highly prevalent issue, there is still much that is not known or understood. The classic iron oxidation system is a complex multiphase system formed of wustite, magnetite, and hematite, producing multi-layered scales. Each phase will have independent properties such as thermal coefficients, growth rate, and mechanical properties, etc. Furthermore, each additional alloying element will have different affinities for oxygen and different mobilities in the oxide phases so that oxide morphologies are specific to alloy chemistry. Therefore, blister regimes can be unique to each steel grade resulting in a diverse range of formation mechanisms. Laboratory conditions were selected to simulate industrial hot rolling with temperature ranges approximate to the formation of secondary and tertiary scales in the finishing mills. Samples with composition: 0.15Wt% C, 0.1Wt% Si, 0.86Wt% Mn, 0.036Wt% Al, and 0.028Wt% Cr, were oxidised in a thermo-gravimetric analyser (TGA), with an air velocity of 10litresmin-1, at temperaturesof 800°C, 850°C, 900°C, 1000°C, 1100°C, and 1200°C respectively. Samples were held at temperature in an argon atmosphere for 10minutes, then oxidised in air for 600s, 60s, 30s, 15s, and 4s, respectively. Oxide morphology and Blisters were characterised using EBSD, WDX, nanoindentation, FIB, and FEG-SEM imaging. Blister was found to have both a nucleation and growth process. During nucleation, the scale detaches from the substrate and blisters after a very short period, roughly 10s. The steel substrate is then exposed inside of the blister and further oxidised in the reducing atmosphere of the blister, however, the atmosphere within the blister is highly dependent upon the porosity of the blister crown. The blister crown was found to be consistently between 35-40um for all heating regimes, which supports the theory that the blister inflates, and the oxide then subsequently grows underneath. Upon heating, two modes of blistering were identified. In Mode 1 it was ascertained that the stresses produced by oxide growth will increase with increasing oxide thickness. Therefore, in Mode 1 the incubation time for blister formation is shortened by increasing temperature. In Mode 2 increase in temperature will result in oxide with a high ductility and high oxide porosity. The high oxide ductility and/or porosity accommodates for the intrinsic stresses from oxide growth. Thus Mode 2 is the inverse of Mode 1, and incubation time is increased with temperature. A new phenomenon was reported whereby blister formed exclusively through cooling at elevated temperatures above mode 2.

Keywords: FEG-SEM, nucleation, oxide morphology, surface defect

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Authors: Staci McGill, Morgan Hayes, Robert Coleman, Kimberly Tumlin

Abstract:

The interaction and relationships between horses and humans have been shown to be positive for physical, mental, and emotional wellbeing, however equine spaces where these interactions occur do include some environmental risks. There are 1.7 million jobs associated with the equine industry in the United States in addition to recreational riders, owners, and volunteers who interact with horses for substantial amounts of time daily inside built structures. One specialized facility, an “indoor arena” is a semi-indoor structure used for exercising horses and exhibiting skills during competitive events. Typically, indoor arenas have a sand or sand mixture as the footing or surface over which the horse travels, and increasingly, silica sand is being recommended due to its durable nature. It was previously identified in a semi-qualitative survey that the majority of individuals using indoor arenas have environmental concerns with dust. 27% (90/333) of respondents reported respiratory issues or allergy-like symptoms while riding with 21.6% (71/329) of respondents reporting these issues while standing on the ground observing or teaching. Frequent headaches and/or lightheadedness was reported in 9.9% (33/333) of respondents while riding and in 4.3% 14/329 while on the ground. Horse respiratory health is also negatively impacted with 58% (194/333) of respondents indicating horses cough during or after time in the indoor arena. Instructors who spent time in indoor arenas self-reported more respiratory issues than those individuals who identified as smokers, highlighting the health relevance of understanding these unique structures. To further elucidate environmental concerns and self-reported health issues, 35 facility assessments were conducted in a cross-sectional sampling design in the states of Kentucky and Ohio (USA). Data, including air speeds, were collected in a grid fashion at 15 points within the indoor arenas and then mapped spatially using krigging in ARCGIS. From the spatial maps, standard variances were obtained and differences were analyzed using multivariant analysis of variances (MANOVA) and analysis of variances (ANOVA). There were no differences for the variance of the air speeds in the spaces for facility orientation, presence and type of roof ventilation, climate control systems, amount of openings, or use of fans. Variability of the air speeds in the indoor arenas was 0.25 or less. Further analysis yielded that average air speeds within the indoor arenas were lower than 100 ft/min (0.51 m/s) which is considered still air in other animal facilities. The lack of air movement means that dust clearance is reliant on particle size and weight rather than ventilation. While further work on respirable dust is necessary, this characterization of the semi-indoor environment where animals and humans interact indicates insufficient air flow to eliminate or reduce respiratory hazards. Finally, engineering solutions to address air movement deficiencies within indoor arenas or mitigate particulate matter are critical to ensuring exposures do not lead to adverse health outcomes for equine professionals, volunteers, participants, and horses within these spaces.

Keywords: equine, indoor arena, ventilation, particulate matter, respiratory health

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