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Mechanically stimulated osteocytes promote the proliferation and migration of breast cancer cells via a potential CXCL1/2 mechanism
No full textBone represents the most common site for breast cancer metastasis. Bone is a highly dynamic organ that is constantly adapting to its biophysical environment, orchestrated largely by the resident osteocyte network. Osteocytes subjected to physiologically relevant biophysical conditions may therefore represent a source of key factors mediating breast cancer cell metastasis to bone. Therefore, we investigated the potential proliferative and migratory capacity of soluble factors released by mechanically stimulated osteocytes on breast cancer cell behaviour. Interestingly the secretome of mechanically stimulated osteocytes enhanced both the proliferation and migration of cancer cells when compared to the secretome of statically cultured osteocytes, demonstrating that mechanical stimuli is an important physiological stimulus that should be considered when identifying potential targets. Using a cytokine array, we further identified a group of mechanically activated cytokines in the osteocyte secretome, which potentially drive breast cancer metastasis. In particular, CXCL1 and CXCL2 cytokines are highly expressed, mechanically regulated, and are known to interact with one another. Lastly, we demonstrate that these specific factors enhance breast cancer cell migration independently and in a synergistic manner, identifying potential osteocyte derived factors mediating breast cancer metastasis to bone
Adsorption of thallium from wastewater using disparate nano-based materials: A systematic review
No full textDevelopment of promising technologies to remove thallium as a highly poisonous contaminant is of great attention to guarantee the sustainable supplement of safe potable water and human well-being all around the world. Recently, adsorption has been introduced as a noteworthy technique to remove trace amount of thallium. In the past, the rate of thallium removal using the adsorption technique was relatively low due to the fact that this method was significantly influenced by the co-existing cations. To overcome this problem, more promising adsorbents such as nano-based materials have been developed. These adsorbents have shown great potential in the process of thallium removal due to their large surface area and superior selectivity. The main objective of
this paper is to present a state-of-the-art review about the potential of nano-based form of disparate materials (i.e., titanium compounds, MnO2, ZnO, Al2O3 and multiwall carbon nanotubes) to separate thallium from water/waste water sources. Then, a systematic overview about acute/chronic toxicities of thallium for humans is aimed to be provided. Throughout the review, the authors aim to compare the negative and positive aspects of each treatment technique and offer promising technologies for thallium removal. At the end, an outlook on the recent advancements in the adsorption process of thallium using nanomaterials is provided
Quality 4.0 conceptualization and theoretical understanding: A global exploratory qualitative study
No full textThis study provides a theoretical base for the Quality 4.0 body of knowledge in terms of an organisation s adoption and overcoming implementation challenges and providing examples of Quality 4.0 application. Organisations can use this study to understand what Quality 4.0 means to industry, the benefits and motivating factors for implementing, the Critical Success Factors, challenges, the organisational readiness factors, and the role of leadership in a Quality 4.0 deployment. In addition, the study looks at the skills required by future Quality 4.0 professionals in terms of hard skills, soft skills and a curriculum for educating future Quality management professionals. The respondents cited that predictive analytics, sensors and tracking, and electronic feedback loops are the most critical technologies for driving Quality 4.0
A core outcome set for the treatment of pregnant women with pregestational diabetes: An international consensus study
No full textBackground
Meaningful comparisons between studies evaluating interventions of pregnant women with pre-gestational diabetes mellitus (PGDM) are limited due to the heterogeneity in outcome selection and reporting. The aim of this study was to develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with PGDM.
Research Design and Methods
The study consisted of three components. 1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. 2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). 3) A consensus meeting where stakeholders from each group decided on the final COS.
Results
We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Two hundred and five stakeholders completed round 1 of the eDelphi survey, of whom 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants of the consensus meeting chose 19 outcomes for inclusion in the final COS: trimester specific HbA1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy induced hypertension, pre-eclampsia, maternal death, birth weight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death.
Conclusions
This COS will enable better comparisons between RCTs, allowing robust evidence synthesis. The COS will improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM
DELA Corpus - A Document-Level Corpus Annotated with Context-Related Issues
No full textRecently, the Machine Translation (MT) community has become more interested in document-level evaluation especially in light of reactions to claims of "human parity", since examining the quality at the level of the document rather than at the sentence level allows for the assessment of suprasentential context, providing a more reliable evaluation.
This paper presents a document-level corpus annotated in English with context-aware issues that arise when translating from English into Brazilian Portuguese, namely ellipsis, gender, lexical ambiguity, number, reference, and terminology, with six different domains. The corpus can be used as a challenge test set for evaluation and as a training/testing corpus for MT as well as for deep linguistic analysis of context issues. To the best of our knowledge, this is the first corpus of its kind
Exploring patients\u27 experience of dental implant surgery with or without intravenous conscious sedation: a qualitative study
No full textAim: Little qualitative evidence is available regarding the patients’ experience of dental implant surgery and the influence of intravenous conscious sedation (IVCS) on the implant experience. The aim of this qualitative study was to explore patients’ experience of dental implant surgery with or without IVCS, with specific consideration given to understanding the patients’ preferences, motivations, needs and values.
Methods: Purposive sampling was used to recruit patients from the Dental Surgery Unit of Cork University Dental School and Hospital. A trained facilitator convened the individual in-depth semi-structured interviews over the telephone 7 days’ post-surgery. Interviews were audio-recorded with a Dictaphone, manually transcribed and imported into a qualitative software tool (Nvivo). The data were then analysed using a thematic framework.
Results: Eighteen semi-structured telephone interviews were conducted; 8 patients had dental implants placed under IVCS, while 10 had dental implants placed with local anaesthetic (LA) only.
Thematic analysis revealed that emergent themes fitted appropriately with 3 different time points along the dental implant surgical journey (Pre-operative, Intra-operative and Post-operative experiences). Data and analysis were categorized, therefore, to follow the patients experience in chronological order. This facilitated narration of the patients accounts of the experience in an explicit way. Preoperative themes that emerged included the impact of tooth lost, motivations for seeking dental implants and dental anxiety. Intraoperative themes included confidence in the operating surgeon, local anaesthetic injections, the dental implant drill and being sedated. While post-operative themes that emerged were pain, postoperative instructions and follow up.
Conclusions: This research offers clinicians deeper understandings of the patients’ experience of dental implant surgery, their preferences, motivations, needs and values, as well as the adjunctive effects of IVCS. Moreover, this research offers ways to improve clinical communications based on the patients’ views and suggestions and ultimately enhancing the quality of patient care
Discovery and molecular characterisation of novel bacteriocins produced by Gram positive bacteria
No full textBacteriocins are ribosomally synthesised antimicrobial peptides, produced by many bacterial genera that display potent activity against closely (narrow spectrum) or distantly related (broad-spectrum) bacteria. Bacteriocins, produced by Lactic Acid Bacteria (LAB) that are natural constituents of fermented foods, are ideal natural preservatives to control food spoilage/pathogenic bacteria in minimally processed foods. In addition to their role as food preservatives, bacteriocins have potent activity against medically significant pathogens and are considered attractive alternatives or adjuncts to antibiotics, due to their inherent heat stability, potency at nanomolar scale, resistance to proteases and low levels of acquired resistance in commercial applications. Overall, bacteriocins are versatile antimicrobials with huge potential for use as biopreservatives, antibiotic alternatives, health promoting gut modulators and animal growth promotors. The aim of this thesis was to identify, purify and characterise novel bacteriocins from microorganisms isolated from a wide range of niches, with a view to expanding the number of bacteriocins currently available and exploring novel structures and activities.
In this respect, Chapter 2.1 describes the discovery a novel nisin A variant, nisin H, produced by a porcine gut isolate Streptococcus hyointestinalis DPC6484. Nisin H differs from nisin A at five amino acid positions and is an intermediate between naturally occurring nisins of lactococcal and streptococcal origin. The operon encoding nisin H is noteworthy by virtue of the absence of an equivalent of nisI that encodes an immunity protein that protects the cell from its own bacteriocin. This is the first report of natural nisin variant production by an intestinal isolate of streptococcal origin and may confer an advantage to the strain by allowing it to dominate its environment, fight infection or signal the immune system of the host. In a subsequent chapter another natural variant is characterised in the form of nisin J, produced by a human skin isolate Staphylococcus capitis APC2923. Nisin J is more dissimilar to nisin A than nisin H with nine amino acid changes, six of which are unique, and an extra amino acid making it the first nisin variant to contain 35 amino acids. Interestingly, the operon lacks both nisI (immunity) and nisRK (regulatory) equivalents. Nisin J, like nisin A and H, displays activity against a wide number of genera and represents the first natural nisin variant from staphylococci and the first nisin producer from human skin, suggesting a role in competitive colonization for producing organisms.
The natural nisin variants described above (nisin H and J), in addition to nisin P produced by Streptococcus agalactiae DPC7040, are all produced by non GRAS strains and are therefore limited in their potential industrial applications. The recent increase in the prevalence of antibiotic resistant pathogens makes it important that all bacteriocins regardless of the producing organism are explored as antibiotic alternatives. As these lantibiotics are gene encoded, bioengineering (Chapter 3.1) was used to enable recombinant expression of peptides naturally expressed by non-GRAS organisms in a host derived from safe origins. Specifically, the Nisin A promotor and nisin A leader sequence were fused to nisin H, J or P structural genes and successfully expressed in the GRAS strain L. lactis NZ9700, demonstrating that the L. lactis production, transport and modification machinery can produce fully functional nisin variants from significantly different genetic backgrounds.
In Chapter 4, Bactofencin A produced by Streptococcus salivarius DPC6502 was discovered following a porcine gut mining study. It is a 22 amino acid, class IId bacteriocin that displays activity against Staphylococcus aureus and Listeria monocytogenes. Structurally, it consists of a positively charged N terminus that we propose could bind to the negatively charged cell surface. The small bacteriocin cluster also encodes a DltB homologue that may well be responsible for immunity through D-alanylation of teichoic acids. In order to probe structure/function relationships in bactofencin A, a library of synthetic bactofencin A peptide variants were synthesized. Substituting cysteine residues significantly reduced activity confirming the importance of the disulphide while sequential removal of the positively charged N terminal resulted in a decreasingly active peptide. Substituting each amino acid for alanine revealed that residues 9-17 within the loop were more affected by substitution, suggesting this region contributes significantly to the potency of the bacteriocin.
In Chapter 5, bactofencin A was shown to enhance nisin bactericidal activity and reduce the overall frequency of resistance. Interestingly, these studies highlighted the relatively slow or delayed mode of action of bactofencin A.
The last two chapters (Chapters 6.1 and 6.2) again focus on the discovery of two novel bacteriocins, namely formicin and actifensin. The first of these, formicin, is a novel bacteriocin that extends the class of two peptide lantibiotics. It was purified from Bacillus paralicheniformis APC1576, a mackerel intestine isolate. Compared with other two component lantibiotics, formicin is most similar to haloduracin and consists of a very hydrophilic Alpha peptide with a charge of +2 whereas the Beta peptide is negatively charged. Formicin displays activity against a broad range of Gram-positive bacteria including clinically relevant pathogens. The second bacteriocin is actifensin a 4091 Da, broad spectrum, Class IId bacteriocin containing three disulphide bridges with more than 50% similarity to eukaryotic defensins that we propose represents a new subclass of bacteriocins. It is produced by Actinomyces ruminicola, isolated from sheep feces. A pangenomic screen of available Actinomyces spp. revealed the presence of very diverse actifensin homologues in 29% of genomes examined, suggesting that production of actifensin like bacteriocins is a common trait. This new class of bacteriocins may provide a template to design new broad-spectrum antimicrobials for treatment of human and animal infections.
The developments described in this thesis can be used to contribute to increased commercialisation of bacteriocins in both food systems and human and animal medical treatments
A comparative reactivity study of 1-alkene fuels from ethylene to 1-heptene
No full textA comparative reactivity study of 1-alkene fuels from ethylene to 1-heptene has been performed using ignition delay time (IDT) measurements from both a high-pressure shock tube and a rapid compression machine, at an equivalence ratio of 1.0 in ‘air’, at a pressure of 30 atm in the temperature range of 600–1300 K. At low temperatures ( 950 K), the experimental results show that all of the fuels except propene show very similar fuel reactivity, with the IDTs of propene being approximately four times longer than for all of the other 1-alkenes. To analyze the experimental results, a chemistry mechanism has been developed using consistent rate constants for these alkenes. At 650 K, flux analyses show that hydroxyl radicals add to the double bond, followed by addition to molecular oxygen producing hydroxy‑alkylperoxy radicals, which can proceed via the Waddington mechanism or alternate internal H-atom isomerizations in chain branching similar to those for alkanes. We have found that the major chain propagation reaction pathways that compete with chain branching pathyways mainly produce hydroxyl rather than hydroperoxyl radicals, which explains the less pronounced NTC behavior for larger 1-alkenes compared to their corresponding alkanes. At 1200 K, flux analyses show that the accumulation of hydroperoxyl radicals is important for the auto-ignition of 1-alkenes from propene to 1-heptene. The rate of production of hydroperoxyl radicals for 1-alkenes from 1-butene to 1-heptene is higher than that for propene, which is due to the longer carbon chain facilitating hydroperoxyl radical formation via more efficient reaction pathways. This is the major reason that propene presents lower fuel reactivity than the other 1-alkenes at high temperatures.The authors at NUI Galway recognize funding support from Science Foundation Ireland (SFI) via their Research Centre Program through project number 16/SP/3829 and also funding from Computational Chemistry LLC. The work at LLNL was performed under the auspices of the U.S. Department of Energy (DOE) by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 and was conducted as part of the Co-Optimization of Fuels & Engines (Co-Optima) project sponsored by the DOE Office of Energy Efficiency and Renewable Energy (EERE), Bioenergy Technologies and Vehicle Technologies Offices
An experimental and detailed kinetic modeling study of the pyrolysis and oxidation of allene and propyne over a wide range of conditions
No full textAllene and propyne are important intermediates in the pyrolysis and oxidation of higher hydrocarbon fuels, and they are also a major source of propargyl radical formation, which can recombine into different C 6 H 6 isomers and finally produce soot. In a prior work (Panigrahy et al., ¿A comprehensive experimental and improved kinetic modeling study on the pyrolysis and oxidation of propyne¿, Proc. Combust. Inst 38 (2021)), the pyrolysis, ignition , and laminar flame speed of propyne were investigated. To understand the kinetic features of initial fuel breakdown and oxidation of the two C 3 H 4 isomers, new measurements for allene pyrolysis and oxidation are conducted in the present paper at the same operating conditions as those studied previously for propyne. Ignition delay times of allene are measured using a high-pressure shock tube and a heated twin-opposed piston rapid compression machine in the temperature range 690¿1450 K at equivalence ratios of 0.5, 1.0 and 2.0 in `air¿, and at pressures of 10 and 30 bar. Pyrolysis species measurements of allene and propyne are also performed using a gas chromatography integrated single- pulse shock tube in the temperature range 10 0 0¿170 0 K at pressure of 2 and 5 bar. Furthermore, laminar flame speeds of allene are measured at elevated gas temperatures of 373 K at pressures of 1 and 2 bar for a wide range of equivalence ratios from 0.6 to 1.5. A newly updated kinetic mechanism developed for this study is the first model that can well reproduce all of the experimental results for both allene and propyne. It is observed that in the pyrolysis process, allene dissociates faster than propyne. Both isomers exhibit similar ignition delay times at high temperatures ( > 10 0 0 K), while, at intermediate temperatures (770¿10 0 0 K) propyne is the faster to ignite, and at lower temperatures (The authors acknowledge Science Foundation Ireland for funding via their Principal Investigator Program through project number 15/IA/3177 and 16/SP/3829. Jinhu Liang acknowledges the support from the National Natural Science Foundation of China (11602231), International Scientific Cooperation Projects of Key R&D Programs (201803D421101), Research Project supported by Shanxi Scholarship Council of China (2020115), and the Young Academic Leaders Support Program of North University of China (QX201810). The material for measuring flame speed is based upon work supported by the U.S. Department of Energy\u27s Office of Energy Efficiency and Renewable Energy (EERE) under Award Number DE-EE0007984 (Co-Optima)
Understanding the antagonistic effect of methanol as a component in surrogate fuel models: A case study of methanol/n-heptane mixtures
No full textMethanol is a widely used engine fuel, blend component, and additive. However, no systematic auto-ignition data or laminar flame speed measurements are available for kinetic studies of the effect of methanol as a blending or additive component. In this work, both ignition delay times and laminar flame speeds of pure methanol, n-heptane and their blends at various blending ratios were measured at engine-relevant conditions. Results show that increasing methanol in a blend promotes reactivity at high temperatures and inhibits it at low temperatures, with the crossover temperature occurring at approximately 970¿980 K with it being almost independent of pressure. The experimental data measured in this work, together with those in the literature are used to validate NUIGMech1.1, which predicts well the experimental ignition delay times and laminar flame speeds of the pure fuels and their blends over a wide range of conditions. Furthermore, kinetic analyses were conducted to reveal the effects of methanol addition on the oxidation pathways of n-heptane and the dominant reactions determining the fuel reactivities. It is found that competition for ¿H radicals between methanol and n-heptane plays an important role in the auto-ignition of the fuel blends at low temperatures. At high temperatures, methanol produces higher concentrations of H¿2 radicals which produce two ¿H radicals either through the production of H2O2 and its subsequent decomposition or through direct reaction with ¿ atoms. This promotes the high temperature reactivity of methanol/n-heptane mixtures for ignition delay times and laminar flame speeds, respectively.This work is supported by the National Natural Science Foundation of China (51722603). The work at NUI Galway is supported by Science Foundation Ireland (SFI) via grant awards 15/IA/3177 and 16/SP/3829. Yingtao Wu would like to thank the financial support from the China Scholarship Council (No. 201806280105). Jinhu Liang acknowledges the support from the International Scientific Cooperation Projects of Key R&D Programs (201803D421101)