Virtual libraries of tissue and clinical samples: potential role of a 3-D microscope.

Our international innovative teaching group from different European Universities (De Montfort University, DMU, UK; and the Spanish University of Alcalá, University Miguel Hernández and University of San Pablo CEU), in conjunction with practicing biomedical scientists in the National Health Service (UK) and biomedical researchers, are developing two complete e-learning packages for teaching and learning medical parasitology, named DMU e-Parasitology (accessible at: http://parasitology.dmu.ac.uk), and biology and chemistry, named DMU e-Biology (accessible at: http://parasitology.dmu.ac.uk/ebiology/index.htm), respectively. Both packages will include a virtual microscope with a complete library of digitised tissue images, clinical slides and cell culture slides/mini-videos for enhancing the teaching and learning of a myriad of techniques applicable to health science undergraduate and postgraduate students. Thus, these packages include detecting human parasites, by becoming familiar with their infective structures and/or organs (e.g. eggs, cysts) and/or explore pathogenic tissues stained with traditional (e.g. haematoxylin & eosin) or more modern (e.g. immunohistochemistry) techniques. The Virtual Microscope (VM) module in the DMU e-Parasitology package is almost completed (accessible at: http://parasitology.dmu.ac.uk/learn/microscope.htm) and contains a section for the three major groups of human-pathogenic parasites (Peña-Fernández et al., 2018) [1]. Digitised slides are provided with the functionality of a microscope by using the gadget Zoomify®, and we consider that they can enhance learning, as previous studies reported in the literature have reported similar sensitivity and specificity rates for identification of parasites for both digitised and real slides. The DMU e-Biology’s VM, currently in development, will provide healthy and pathological tissue samples from a range of mammalian tissues and organs. This communication will provide a description of both virtual libraries and the process of developing them. In conjunction, we will use a three-dimensional (3D) super-resolution microscopy, 3D Cell Explorer (Nanolive, Lausanne, Switzerland), to incorporate potential 3D microscopic photographs/short videos of cells to provide students with information about the spatial arrangement and morphologies of cells that are essential for life

Ideas and Enhancements Related to Mobile Applications to Support Type 1 Diabetes

Background: Mobile devices have become increasingly important to young people who now use them to access a wide variety of health-related information. Research and policy related to the integration of health information and support with this technology do not effectively consider the viewpoint of a younger patient. Views of young people with type 1 diabetes are vital in developing quality services and improving their own health-related quality of life (HRQOL), yet research on their lifestyle and use of Web and mobile technology to support their condition and in non–health-related areas is sparse. Objective: To develop insight into young people with type 1 diabetes and their current use of Web and mobile technology and its potential impact on HRQOL. This can be achieved by constructing an in-depth picture of their day-to-day experiences from qualitative interviewing and exploring how they make use of technology in their lives and in relation to their condition and treatment. The goal was then to build something to help them, using the researcher’s technical expertise and seeking users’ opinions during the design and build, utilizing sociotechnical design principles. Methods: Data were collected by semistructured, in-depth qualitative interviews (N=9) of young people with type 1 diabetes aged 18-21. Interviews were transcribed and loaded onto NVivo for theme identification. Data analysis was undertaken during initial interviews (n=4) to locate potential ideas and enhancements for technical development. Latter interviews (n=5) assisted in the iterative sociotechnical design process of the development and provided additional developmental ideas. Results: Six themes were identified providing an understanding of how participants lived with and experienced their condition and how they used technology. Four technological suggestions for improvement were taken forward for prototyping. One prototype was developed as a clinically approved app. A number of ideas for new mobile apps and enhancements to currently existing apps that did not satisfactorily cater to this age group’s requirements for use in terms of design and functionality were suggested by interviewees but were not prototyped. Conclusions: This paper outlines the nonprototyped suggestions from interviewees and argues that young people with type 1 diabetes have a key role to play in the design and implementation of new technology to support them and improve HRQOL. It is vital to include and reflect on their suggestions as they have a radically different view of technology than either their parents or practitioners. We need to consider the relationship to technology that young people with type 1 diabetes have, and then reflect on how this might make a difference to them and when it might not be a suitable mechanism to use

Nitrogen isotopic evidence for deglacial changes in nutrient supply in the eastern equatorial Pacific

The Eastern Equatorial Pacific (EEP) is a high nutrient–low chlorophyll region of the ocean. Downcore nitrogen isotope records from the EEP have been previously interpreted as a direct reflection of changes in nutrient consumption. However, the observed changes in sedimentary δ15N since the last glacial maximum have no coherent relationship with export productivity or an inferred variation in the iron‐to‐nitrate ratio of the surface waters. Rather, downcore N isotope records in the EEP strongly resemble changes in the extent of water column denitrification as recorded in nearby sedimentary δ15N records along the western margin of the Americas. This similarity is attributed to the overprinting of the N isotopic composition of nitrate in the EEP through the advection of nitrate westward from the margins in the subsurface. A local nitrogen isotope record of changes in the degree of nutrient consumption is extracted from the bulk sedimentary record by subtracting two different sedimentary δ15N records of denitrification changes from two new EEP δ15N records (TR163‐22 and ODP Site 1240). The denitrification records used are from 1) the Central American margin (ODP Site 1242) and 2) the South American margin (GeoB7139‐2). The degree of consumption in the surface waters declines rapidly from elevated values during the last glacial maximum to a pair of minima around 15 and 11–13 ka, and finally it increases into the Holocene. The derived EEP nitrogen isotope record indicates that the regional peak in export productivity occurred when the supply of nutrients exceeded the apparently high demand. The influx of nutrients during the deglaciation is attributed to the resumption of intense overturning in the Southern Ocean and the release of sequestered CO2 and nutrient‐rich, O2 poor waters from the deep ocean. This has important implications for understanding the glacial‐interglacial scale variation in intermediate water suboxia and water column denitrification

Climate fluctuations during the Holocene in NW Iberia: high and low latitude linkages

International audienceHigh resolution benthic foraminiferal oxygen and carbon stable isotopes (?18O, ?13C) from core EUGC-3B are used here to infer rapid climatic changes for the last 8500 yr in the Ría de Muros (NW Iberian Margin). Benthic foraminiferal ?18O and ?13C potentially register migrations in the position of the hydrographic front formed between two different intermediate water masses: Eastern North Atlantic Central Water of subpolar origin (ENACWsp), and subtropical origin (ENACWsp). The isotopic records have been compared with two well established North Atlantic marine Holocene paleoceanographic records from low (Sea Surface Temperatures anomalies off Cape Blanc, NW Africa) and high latitudes (Hematite Stained Grains percentage, subpolar North Atlantic). This comparison clearly demonstrates that there is a strong link between high- and low-latitude climatic perturbations at centennial-millennial time scales during the Holocene. Spectral analyses also points at a pole-to-equator propagation of the so-called 1500 yr cycles. Our results demonstrate that during the Holocene, the NW Iberian Margin has undergone a series of cold episodes which are likely triggered at high latitudes in the North Atlantic and are rapidly propagated towards lower latitudes. Conceivably, the propagation of these rapid climatic changes involves a shift of atmospheric and oceanic circulatory systems and so a migration of the hydrographical fronts and water masses all along the North Atlantic area

Functional evaluation and testing of a newly developed Teleost’s Fish Otolith derived biocomposite coating for healthcare

Polymers such as polycaprolactone (PCL) possess biodegradability, biocompatibility and affinity with other organic media that makes them suitable for biomedical applications. In this work, a novel biocomposite coating was synthesised by mixing PCL with layers of calcium phosphate (hydroxyapatite, brushite and monetite) from a biomineral called otolith extracted from Teleost fish (Plagioscion Squamosissimus) and multiwalled carbon nanotubes in different concentrations (0.5, 1.0 and 1.5 g/L). The biocomposite coating was deposited on an osteosynthesis material Ti6Al4V by spin coating and various tests such as Fourier transformation infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), scratch tests, MTT reduction cytotoxicity, HOS cell bioactivity (human osteosarcoma) by alkaline phosphatase (ALP) and fluorescence microscopy were performed to comprehensively evaluate the newly developed biocoating. It was found that an increase in the concentration of carbon nanotube induced microstructural phase changes of calcium phosphate (CP) leading to the formation of brushite, monetite and hydroxyapatite. While we discovered that an increase in the concentration of carbon nanotube generally improves the adhesion of the coating with the substrate, a certain threshold exists such that the best deposition surfaces were obtained as PCL/CP/CNT 0.0 g/L and PCL/CP/CNT 0.5 g/L

Stress-strain behavior and geometrical properties of packings of elongated particles

We present a numerical analysis of the effect of particle elongation on the quasistatic behavior of sheared granular media by means of the Contact Dynamics method. The particle shapes are rounded-cap rectangles characterized by their elongation. The macroscopic and microstructural properties of several packings subjected to biaxial compression are analyzed as a function of particle elongation. We find that the shear strength is an increasing linear function of elongation. Performing an additive decomposition of the stress tensor based on a harmonic approximation of the angular dependence of branch vectors, contact normals and forces, we show that the increasing mobilization of friction force and the associated anisotropy are key effects of particle elongation. These effects are correlated with partial nematic ordering of the particles which tend to be oriented perpendicular to the major principal stress direction and form side-to-side contacts. However, the force transmission is found to be mainly guided by cap-to-side contacts, which represent the largest fraction of contacts for the most elongated particles. Another interesting finding is that, in contrast to shear strength, the solid fraction first increases with particle elongation, but declines as the particles become more elongated. It is also remarkable that the coordination number does not follow this trend so that the packings of more elongated particles are looser but more strongly connected.Comment: Submited to Physical Review

Non-perturbative renormalisation and improvement of non-singlet tensor currents in Nf=3N_\mathrm{f}=3 QCD

Hadronic matrix elements involving tensor currents play an important r\^ole in decays that allow to probe the consistency of the Standard Model via precision lattice QCD calculations. The non-singlet tensor current is a scale-dependent (anomalous) quantity. We fully resolve its renormalisation group (RG) running in the continuum by carrying out a recursive finite-size scaling technique. In this way ambiguities due to a perturbative RG running and matching to lattice data at low energies are eliminated. We provide the total renormalisation factor at a hadronic scale of 233 MeV, which converts the bare current into its RG-invariant form. Our calculation features three flavours of O(a) improved Wilson fermions and tree-level Symanzik-improved gauge action. We employ the (massless) Schr\"odinger functional renormalisation scheme throughout and present the first non-perturbative determination of the Symanzik counterterm $c_\mathrm{T}$ derived from an axial Ward identity. We elaborate on various details of our calculations, including two different renormalisation conditions.Comment: 39 pages, 10 figures, 11 tables

Deficiency of Kruppel-Like Factor KLF4 in Myeloid-Derived Suppressor Cells Inhibits Tumor Pulmonary Metastasis in Mice Accompanied by Decreased Fibrocytes

The importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) bearing monocyte markers in tumor metastasis has been well established. Recently, it was reported that these cells possess phenotypic plasticity and differentiate into fibrocytes, very distinct cells that are precursors of tumorigenic myofibroblasts. However, the importance of this transdifferentiation in tumor metastasis has not been explored. Here, we describe the role of MDSC-derived fibrocytes in tumor metastasis that is regulated by Kruppel-like factor 4 (KLF4), a transcription factor that is critical to monocyte differentiation and to promotion of cancer development. Using mouse metastasis models of melanoma and breast cancer, we found that KLF4 knockout was associated with significantly reduced pulmonary metastasis, which was accompanied by decreased populations of MDSCs, fibrocytes and myofibroblasts in the lung. Cause-effect studies by adoptive transfer revealed that KLF4 deficiency in MDSCs led to significantly reduced lung metastasis that was associated with fewer MDSC-derived fibrocytes and myofibroblasts. Mechanistically, KLF4 deficiency significantly compromised the generation of fibrocytes from MDSCs in vitro. During this process, KLF4 expression levels were tightly linked with those of fibroblast-specific protein-1 (FSP-1), deficiency of which resulted in no metastasis in mice as has been previously reported. In addition, KLF4 bound directly to the FSP-1 promoter as determined by chromatin immunoprecipitation and overexpression of KLF4 increased the FSP-1 promoter activities. Taken together, our results suggest that MDSCs not only execute their immunosuppressive function to promote metastatic seeding as reported before, but also boost metastatic tumor growth after they adopt a fibrocyte fate. Therefore, KLF4-mediated fibrocyte generation from MDSCs may represent a novel mechanism of MDSCs contributing to tumor metastasis and supports the feasibility of inhibiting KLF4 or FSP-1 to prevent tumor metastasis

Brownian Entanglement

We show that for two classical brownian particles there exists an analog of continuous-variable quantum entanglement: The common probability distribution of the two coordinates and the corresponding coarse-grained velocities cannot be prepared via mixing of any factorized distributions referring to the two particles in separate. This is possible for particles which interacted in the past, but do not interact in the present. Three factors are crucial for the effect: 1) separation of time-scales of coordinate and momentum which motivates the definition of coarse-grained velocities; 2) the resulting uncertainty relations between the coordinate of the brownian particle and the change of its coarse-grained velocity; 3) the fact that the coarse-grained velocity, though pertaining to a single brownian particle, is defined on a common context of two particles. The brownian entanglement is a consequence of a coarse-grained description and disappears for a finer resolution of the brownian motion. We discuss possibilities of its experimental realizations in examples of macroscopic brownian motion.Comment: 18 pages, no figure