Glycosidase activity in the excretory-secretory products of the liver fluke, Fasciola hepatica

Fasciola hepatica secretes proteolytic enzymes and other molecules that are essential for host penetration and migration. This mixture may include enzymes required for the degradation of supramucosal gels, which defend epithelial surfaces against pathogen entry. These contain hydrated mucins that are heavily glycosylated. Excretory-secretory products (ES) from F. hepatica were examined for a range of glycosidase activities, using synthetic 4-methylumbelliferyl glycosides as substrates. The ES product contained at least 8 different glycosidase activities, the most abundant of which were β-N- acetylhexosaminidase, β-galactosidase and β-glucosidase. Alpha-fucosidase, β-glucuronidase, α-galactosidase, α-mannosidase and neuraminidase were also present. β-N- acetylhexosaminidase and β-galactosidase were present in multiple isoforms (at least 4), whereas β-glucosidase appeared to exist as one isoenzyme with a pI <3.8. All three enzymes had acidic pH optima (4.5-5.0). Ovine small intestinal mucin was degraded by ES at pH 4.5 or 7.0, with or without active cathepsin L, the major protease found in F. hepatica ES. The ability of F. hepatica ES to degrade mucin in the presence or absence of active cathepsin L suggests that cathepsin L is not essential for mucin degradation. The abundance of β-galactosidase and β-hexosaminidase in ES supports a role for these enzymes in mucin degradation

Higher Structures in M-Theory

The key open problem of string theory remains its non-perturbative completion to M-theory. A decisive hint to its inner workings comes from numerous appearances of higher structures in the limits of M-theory that are already understood, such as higher degree flux fields and their dualities, or the higher algebraic structures governing closed string field theory. These are all controlled by the higher homotopy theory of derived categories, generalised cohomology theories, and $L_\infty$-algebras. This is the introductory chapter to the proceedings of the LMS/EPSRC Durham Symposium on Higher Structures in M-Theory. We first review higher structures as well as their motivation in string theory and beyond. Then we list the contributions in this volume, putting them into context.Comment: 22 pages, Introductory Article to Proceedings of LMS/EPSRC Durham Symposium Higher Structures in M-Theory, August 2018, references update

A new method for assessing the recyclability of powders within Powder Bed Fusion process

Recycling metallic powders used in the additive manufacturing (AM) process is essential for reducing the process cost, manufacturing time, energy consumption, and metallic waste. In this paper, the focus is on pore formation in recycled powder particles of stainless steel 316L during the selective laser melting process. We have introduced the concept of optimizing the powder bed's printing area in order to see the extent of the affected powders during the 3D-printing process. X-ray Computed Tomography (XCT) is used to characterize the pores inside the particles. The results from image processing of the tomography (rendered in 3D format) indicate a broader pore size distribution and a higher pore density in recycled powders compared to their virgin counterparts. To elucidate on this, the Electron Dispersion spectroscopy (EDX) analysis and Synchrotron-based Hard X-ray Photoelectron Spectroscopy (HAXPES) were performed to reveal the chemical composition distribution across the pore area and bulk of the recycled powder particles. Higher concentrations of Fe, Cr, and Ni were recorded on the interior wall of the pore in recycled particles and higher Mn, S and Si concentrations were recorded in the outer layer around the pore area and on the surface of the recycled particle. The pore formation in recycled powder is attributed to out-diffusion of Mn, S and Si to the outer surface as a result of the incident laser heat during the AM process due to higher electron affinity of such metallic elements to oxygenation. HAXPES analysis shows a higher MnO concentration around the pore area which impedes the in-diffusion of other elements into the bulk and thereby helps to creates a void. The inside wall of the pore area (dendrites), has a higher concentration of Fe and Cr oxide. We believe the higher pore density in recycled powders is due, at least in part to composition redistribution, promoted by laser heat during the AM process. Nanoindentation analyses on both virgin and recycled powder particles shows a lower hardness and higher effective modulus in the recycled powder particles attributed to the higher porosity in recycled powders

From Euclidean Geometry to Knots and Nets

This document is the Accepted Manuscript of an article accepted for publication in Synthese. Under embargo until 19 September 2018. The final publication is available at Springer via https://doi.org/10.1007/s11229-017-1558-x.This paper assumes the success of arguments against the view that informal mathematical proofs secure rational conviction in virtue of their relations with corresponding formal derivations. This assumption entails a need for an alternative account of the logic of informal mathematical proofs. Following examination of case studies by Manders, De Toffoli and Giardino, Leitgeb, Feferman and others, this paper proposes a framework for analysing those informal proofs that appeal to the perception or modification of diagrams or to the inspection or imaginative manipulation of mental models of mathematical phenomena. Proofs relying on diagrams can be rigorous if (a) it is easy to draw a diagram that shares or otherwise indicates the structure of the mathematical object, (b) the information thus displayed is not metrical and (c) it is possible to put the inferences into systematic mathematical relation with other mathematical inferential practices. Proofs that appeal to mental models can be rigorous if the mental models can be externalised as diagrammatic practice that satisfies these three conditions.Peer reviewe

Análisis de factores socio-culturales y ambientales involucrados en problemas de salud prevenibles (diarrea, malnutrición y anemia) en niños de 0 a 4 años en la comunidad de la Zona Sur de Gualeguaychú. Implementación y evaluación de intervenciones

Se realizó un trabajo descriptivo, con matices de diseño exploratorio, que permitió analizar aspectos socio-culturales y ambientales de familias con ocurrencia de enfermedades infantiles prevenibles. Se eligió la diarrea, la desnutrición y anemia por ser patologías prevalentes en niños de 0 a 4 años. Para estas enfermedades su atención consiste, la mayoría de las veces, en brindar alimentación adecuada, considerando el entorno familiar y ambiental. Al concebir la alimentación como un proceso cultural o una condición de vida, que a su vez incluye 4 momentos, se entiende que forma parte del acervo cultural de todo grupo social; y siendo la práctica de atención más frecuente e inmediata de la diarrea, la desnutrición y anemia, se habla del proceso salud/enfermedad/alimentación, esta última entendida como atención. La alimentación entonces refiere a las representaciones sociales de cada grupo, las que se expresan en las prácticas de los actores familiares. De las indagaciones a las familias, estas, no presentaron un correlato entre sus conocimientos y prácticas de cuidados en salud infantil, ello podría relacionarse con las condiciones de vida desfavorables, lo cual indica que se debiera trabajar en pos de los factores protectores, en acciones de promoción enfocadas a las prácticas alimentario nutricionales

Comparative hydrodynamic and nanoscale imaging study on the interactions of teicoplanin-A2 and bovine submaxillary mucin as a model ocular mucin

Glycopeptide antibiotics are regularly used in ophthalmology to treat infections of Gram-positive bacteria. Aggregative interactions of antibiotics with mucins however can lead to long exposure and increases the risk of resistant species. This study focuses on the evaluation of potential interactions of the last line of defence glycopeptide antibiotic teicoplanin with an ocular mucin model using precision matrix free hydrodynamic and microscopic techniques: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), dynamic light scattering (DLS) and atomic force microscopy (AFM). For the mixtures of teicoplanin at higher doses (1.25 mg/mL and 12.5 mg/mL), it was shown to interact and aggregate with bovine submaxillary mucin (BSM) in the distributions of both sedimentation coefficients by SV-AUC and hydrodynamic radii by DLS. The presence of aggregates was confirmed by AFM for higher concentrations. We suggest that teicoplanin eye drop formulations should be delivered at concentrations of < 1.25 mg/mL to avoid potentially harmful aggregations

Self-association of the glycopeptide antibiotic teicoplanin A2 in aqueous solution studied by molecular hydrodynamics

AbstractThe natural glycopeptide antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (M1 = 1880 g/mol) were examined in phosphate chloride buffer (pH 6.8, I = 0.10 M) using sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge together with capillary (rolling ball) viscometry. In the concentration range, 0–10 mg/mL teicoplanin A2 was found to self-associate plateauing &gt; 1 mg/mL to give a molar mass of (35,400 ± 1000) g/mol corresponding to ~ (19 ± 1) mers, with a sedimentation coefficient s20, w =  ~ 4.65 S. The intrinsic viscosity [$$\eta$$ η ] was found to be (3.2 ± 0.1) mL/g: both this, the value for s20,w and the hydrodynamic radius from dynamic light scattering are consistent with a globular macromolecular assembly, with a swelling ratio through dynamic hydration processes of ~ 2. </jats:p

Mathematical practice, crowdsourcing, and social machines

The highest level of mathematics has traditionally been seen as a solitary endeavour, to produce a proof for review and acceptance by research peers. Mathematics is now at a remarkable inflexion point, with new technology radically extending the power and limits of individuals. Crowdsourcing pulls together diverse experts to solve problems; symbolic computation tackles huge routine calculations; and computers check proofs too long and complicated for humans to comprehend. Mathematical practice is an emerging interdisciplinary field which draws on philosophy and social science to understand how mathematics is produced. Online mathematical activity provides a novel and rich source of data for empirical investigation of mathematical practice - for example the community question answering system {\it mathoverflow} contains around 40,000 mathematical conversations, and {\it polymath} collaborations provide transcripts of the process of discovering proofs. Our preliminary investigations have demonstrated the importance of "soft" aspects such as analogy and creativity, alongside deduction and proof, in the production of mathematics, and have given us new ways to think about the roles of people and machines in creating new mathematical knowledge. We discuss further investigation of these resources and what it might reveal. Crowdsourced mathematical activity is an example of a "social machine", a new paradigm, identified by Berners-Lee, for viewing a combination of people and computers as a single problem-solving entity, and the subject of major international research endeavours. We outline a future research agenda for mathematics social machines, a combination of people, computers, and mathematical archives to create and apply mathematics, with the potential to change the way people do mathematics, and to transform the reach, pace, and impact of mathematics research.Comment: To appear, Springer LNCS, Proceedings of Conferences on Intelligent Computer Mathematics, CICM 2013, July 2013 Bath, U

Eleanor Davies and the New Jerusalem

Eleanor Davies was a great believer in historical moments. In her first work—A Warning to the Dragon and All His Angels of 1625-she told readers that “The Lord is at the Dore.”1 This immanence of God made her watchful and purposeful, reading the signs in her daily life, counting days, weeks, and years because she believed that Christ would come again. His arrival had been predestined from the beginning of the world: “from the going forth of the Commandement, which is the beginning of the Creation to the building of the New Jerusalem, the second comming of Messiah, the Prince the Sonne of God, it shall be Seaven Weekes or Seaven Moneths.”2 For Davies, time was elastic, but history was absolute. What the biblical prophets (in this case Ezekiel) said would come to pass, really would come to pass, but their promises were oracular; they had complete authority but were also elusive. Davies accepted this. She knew that she was living in the latter days, but when it came to God’s final judgment, “the daye and houre knoweth no man.”3 God could not be known as such and what she called knowledge was a spiritual transformation that took place when “He powreth out his Spirit upon his hand-maidens,” like herself.4 This essay uses A Warning to the Dragon and Davies’ works of the 1630s and 1640s to examine her theology

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF